ascorbic-acid and Kidney-Diseases

Topics: Ascorbic Acid; Humans; Hyperoxaluria; Kidney; Kidney Diseases; Kidney Transplantation; Oxalates

The purpose of the present study was to evaluate the efficacy of N-acetylcysteine (NAC) versus ascorbic acid (VC) or NAC plus (+) VC on the prevention of contrast-induced nephropathy (CIN) in patients undergoing contrast administration.. We searched databases including Medline, Embase and Cochrane Library up to Feb 22 (th), 2017. Pooled risk ratios (RRs) or weighted mean difference (WMD) with their 95% confidence intervals (CIs) were calculated using fixed-effects model or random-effects model when appropriate. All analyses were performed using the Review Manager 5.2.. A totalof six randomized controlled trials including 919 patients (478 cases received NAC administration and 441 cases received VC or NAC + VC administration) were considered in the meta-analysis. Results showed that there was no significant difference in preventing CIN between NAC and NAC + VC administration as well as between NAC and VC administration. In addition, significant difference was found in serum creatinine level between NAC and VC or NAC + VC administration (WMD = -0.31, 95% CI: -0.48 to -0.14, P = 0.0003) as well as NAC and VC administration (WMD = -0.05, 95% CI: -0.08 to -0.02, P = 0.002). Besides, NAC and NAC + VC administration also has significant difference (WMD = -0.72, 95% CI: -1.33 to -0.11, P = 0.02).. In conclusion, the prevention effect of NAC administration and VC or NAC + VC administration on CIN was similar in patients undergoing contrast administration. But NAC administration was associated with a significantly lower serum creatinine levels compared to VC and NAC + VC administration.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Biomarkers; Chi-Square Distribution; Contrast Media; Creatinine; Drug Therapy, Combination; Humans; Kidney Diseases; Odds Ratio; Protective Factors; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN).. To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media.. MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed.. Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis.. Two reviewers independently extracted data and assessed study quality.. Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N-acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality.. Too few studies were done in patients receiving IV contrast media.. The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline.. Agency for Healthcare Research and Quality.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Contrast Media; Free Radical Scavengers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infusions, Intra-Arterial; Infusions, Intravenous; Kidney Diseases; Odds Ratio; Sodium Bicarbonate; Sodium Chloride; United States

Contrast-induced nephropathy continues to be a common cause of in-hospital acute kidney injury. Published studies on pathogenesis, clinical significance, diagnosis, and preventive measures have dramatically increased significantly in the past several years. This review will focus on new developments in contrast-induced nephropathy.. Studies on the clinical significance of contrast-induced nephropathy are reviewed along with initial reports of biomarkers in diagnosing this complication of iodinated contrast administration. Emerging literature on the relative nephrotoxicity of iso-osmolar versus low-osmolar contrast media and the value of bicarbonate hydration are discussed. More recent preventive measures using prostacyclin, 'statins', and erythropoietin are also reviewed.. Contrast-induced nephropathy is an increasing cause of acute kidney injury and is associated with significant mortality and morbidity. Future developments in this field will focus on refining the clinical significance of this complication, earlier diagnosis with biomarkers, clarifying the role for bicarbonate and iso-osmolar contrast agents as preventive strategies, and the introduction of new prophylactic techniques on the basis of an improved understanding of pathogenesis at the cellular level.

Topics: Acetylcysteine; Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Ascorbic Acid; Contrast Media; Fluid Therapy; Hemofiltration; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Renal Dialysis; Sodium Bicarbonate; Theophylline

Contrast nephropathy is a common complication associated with angiographic procedures that carries significant morbidity and mortality. Recent clinical trials of prophylactic strategies have reported contradictory results. This review presents recent insights into the pathophysiology of contrast nephropathy and reviews trial results in this context.. A prediction rule has been developed to better identify patients at risk of developing contrast nephropathy. Factors other than osmolality play a significant role in the pathogenesis of contrast nephropathy, at least for agents with osmolalities of 800 mOsm/kg or less. New randomized trial data do not support a role for N-acetylcysteine in contrast nephropathy prophylaxis and there is additional evidence that fenoldopam is ineffective. Pooled analyses of theophylline prophylaxis trials are inconclusive. Theoretical and clinical data suggest that ascorbic acid may be renoprotective, but this requires further study.. The overall incidence of contrast nephropathy remains low. Available evidence supports the use of hydration and low volumes of iso-osmolar or low-osmolar contrast in patients at risk of developing contrast nephropathy. Heterogeneity has affected interpretability of interventional trials of N-acetylcysteine or theophylline prophylaxis strategies. Future clinical trials must identify and target moderate-risk to high-risk patients and ensure that proven therapies are included in trial protocols.

Topics: Acetylcysteine; Ascorbic Acid; Contrast Media; Evidence-Based Medicine; Fenoldopam; Humans; Kidney Diseases; Osmolar Concentration; Risk Factors; Theophylline

The immunosuppressive drug cyclosporine A (CsA) has been successfully used in several diseases with immunological basis and in transplant patients. Nephrotoxicity is the main secondary effect of CsA treatment. Although the mechanisms of nephrotoxitity are not completely defined, there is evidence that suggests the role of reactive oxygen species (ROS) in its pathogenesis. It has been demonstrated in numerous in vivo and in vitro experiments that CsA induced renal failure and increased the synthesis of ROS, thromboxane (TX) and lipid peroxidation products in the kidney. Furthermore, CsA modified the expression and activity of several renal enzymes (ciclooxygenase, superoxide-dismutase, catalase and glutathione-peroxidase). Antioxidant nutrients (e.g. Vitamins E and C) can neutralize some of the effects that CsA produced in the kidney. Thus, Vit E inhibited the synthesis of ROS and TX and the lipid peroxidation process induced by CsA in kidney structures. Antioxidants can also improve renal function and histological damage produced by CsA administration. Although there are few data in humans treated with CsA, the possibility exists that antioxidants can also neutralize CsA nephrotoxicity and LDL oxidation. Thus, antioxidant nutrients could have a therapeutic role in transplant patients treated with CsA.

Topics: Animals; Antioxidants; Ascorbic Acid; Cyclosporine; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Lipid Peroxides; Reactive Oxygen Species; Thromboxanes; Vitamin E

In view of the role of oxidative processes in inflicting damage that leads to glomerulosclerosis and renal medullary interstitial fibrosis, more attention could be paid to the use of antioxidant food constituents and the usage of drugs with recognized antioxidant potential. In any case atherosclerosis is an important component of chronic renal diseases. There is a wide choice of foods and drugs that could confer benefit. Supplementation with vitamins E and C, use of soy protein diets and drinking green tea could be sufficient to confer remarkable improvements.

Topics: Animals; Antioxidants; Ascorbic Acid; Dietary Supplements; Food, Organic; Humans; Kidney Diseases; Tea; Vitamin E

The purpose of this article is to review the potential role of nuclear medicine scanning, especially with 67Ga, in the presumptive diagnosis and clinical management of patients with renal parenchymal malacoplakia (RPMP), a rare disease associated with coliform bacterial infection of the kidney and characterized by chronic unresolving inflammatory infiltrates containing von Hansemann macrophages in the renal parenchyma.. Published cases of RPMP were collected from the archival literature by searching the MEDLINE database and by reviewing bibliographic references contained in articles on malacoplakia. Data on the clinical features and radiographic evaluation of patients with RPMP were extracted from the clinical case reports.. Forty-three cases of RPMP published over the past 20 yr were identified. Ten of the 43 patients (23%) had 67Ga scanning as a component of their diagnostic evaluation. In all 10 patients, renal uptake of 67Ga was classified as intense. Two of those 10 patients had serial 67Ga scanning performed to assess response to antibiotic treatment; both patients exhibited decreased uptake or complete resolution of abnormal renal uptake over time, a finding also exhibited by our patient.. Intense renal uptake of 67Ga, typically in the clinical setting of fever, progressive renal failure and nephromegaly, strongly supports a diagnosis of RPMP. In those patients receiving prolonged antimicrobial therapy for RPMP, resolution of abnormal 67Ga uptake over time may provide an objective endpoint for treatment.

Topics: Anti-Infective Agents; Ascorbic Acid; Ciprofloxacin; Citrates; Female; Gallium; Gallium Radioisotopes; Humans; Kidney Diseases; Malacoplakia; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rifampin

The known literature data concerning the mechanisms of molecular action of vitamin E in biological membrane systems are reviewed. The role of vitamin E, possessing a broad range of biological activities, as a universal stabilizer of biological membranes in normal oxygen metabolism and peroxidation, and also in disorders of normal metabolism resulting in pathological alterations, has been discussed. The participation of vitamin E in redox reactions taking place in lipid media, its interaction with singlet oxygen, free fatty acids and enzyme systems are considered. Physiological effects of vitamin E and its ability to prevent numerous pathologies are also considered. Vitamin E was concluded to be a universal participant of antioxidant defence reactions in biological membranes, since it acts at all stages of membrane oxidative damage.

Topics: Aging; Antioxidants; Ascorbic Acid; Fatty Acids, Unsaturated; Free Radicals; Glutathione; Heart Diseases; Humans; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Membranes; Neoplasms; Vitamin E

Malacoplakia is a rare inflammatory disorder seen most often in the urinary tract, where it is highly associated with coliform infection. Although first recognized by pathologists in 1902, it has received little attention from the infectious disease community. While there remains much uncertainty regarding the specific cause of malacoplakia, it appears to be associated with a defect in intracellular killing of ingested microorganisms by macrophages. We report a case of bilateral renal parenchymal malacoplakia that presented as fever of unknown origin, and we review 33 previously identified cases. Renal malacoplakia has traditionally been associated with high morbidity and mortality. More recently, treatment with antimicrobial agents such as trimethoprim or ciprofloxacin has yielded a better outcome than had been documented with other therapy. Malacoplakia should be considered in the evaluation of fever of unknown origin or of relapsing or refractory urinary tract infection. Therapy with antimicrobial agents capable of intracellular penetration is recommended.

Topics: Anti-Infective Agents; Ascorbic Acid; Bethanechol; Bethanechol Compounds; Female; Fever of Unknown Origin; Humans; Kidney Diseases; Malacoplakia; Middle Aged; Urinary Tract Infections

Topics: Amyloidosis; Ascorbic Acid; Biopsy; Humans; Hypoproteinemia; Kidney; Kidney Diseases; Liver Extracts; Microscopy, Electron; Polyuria; Proteinuria

Topics: Ascorbic Acid; Bone and Bones; Calcium; Cell Membrane Permeability; Erythrocytes; Feces; Glycine; Humans; Intestinal Absorption; Intestinal Mucosa; Kidney; Kidney Diseases; Kidney Function Tests; Liver; Metabolism, Inborn Errors; Microsomes; Mitochondria; Muscles; Oxalates; Plants, Edible; Urinary Calculi

The objective of this study was to determine the association between sociodemographic factors and intakes of 4 nutrients and associations between intakes and markers of kidney disease to identify opportunities to improve outcomes among clinically high-risk African Americans.. We conducted a cross-sectional study of baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension in Baltimore MD. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio >=30 mg/g.. Baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension, were obtained.. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease.. Overall, compared to Institute of Medicine recommendations, participants had lower intakes of magnesium, fiber, and potassium but higher vitamin C intakes. For females, sociodemographic factors that significantly associated with lower intake of the 4 nutrients were older age, obesity, lower health numeracy, and lesser educational attainment. For males, none of the sociodemographic factors were significantly associated with nutrient intakes. Below-median intake was significantly associated with albumin-to-creatinine ratio ≥30 (adjusted odds ratio [95% confidence interval]: 3.4 [1.5, 7.8] for vitamin C; 3.6 [1.6, 8.4] for magnesium; 2.9 [1.3, 6.5] for fiber; 3.6 [1.6, 8.4] for potassium), but not with estimated glomerular filtration rate <60.. African Americans with uncontrolled hypertension may have low intakes of important nutrients, which could increase their risk of chronic kidney disease. Tailored dietary interventions for African Americans at high risk for chronic kidney disease may be warranted.

Topics: Aged; Ascorbic Acid; Baltimore; Black or African American; Blood Pressure; Cross-Sectional Studies; Diet; Dietary Fiber; Energy Intake; Female; Humans; Hypertension; Kidney Diseases; Logistic Models; Magnesium; Male; Middle Aged; Nutritional Status; Potassium, Dietary; Socioeconomic Factors; Surveys and Questionnaires; Urban Population

Contrast-induced nephropathy (CIN) is a common and severe complication in interventional cardiology.. The aim of our study was to compare the incidence of contrast-induced nephropathy in two accelerated hydration protocols: the first one by the serum bicarbonate and the second combining the serum bicarbonate and oral vitamin C.. This is a multicenter prospective, randomized study conducted between October 2012 and May 2013, including 160 patients.. The mean age of our study population was 60.8±9.3 years (36-83 years). The two study groups were comparable in terms of cardiovascular risk factors, concomitant medication, and baseline serum creatinine. The CIN incidence was 6.3% in the vitamin C group and 10% in the control group (P=0.38). No significant difference was observed in terms of CIN incidence between the different subgroups analyzed.. According to our study, ascorbic acid administered orally as part of an accelerated hydration protocol does not reduce the incidence of CIN.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Contrast Media; Female; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Sodium Bicarbonate; Vitamins

Several protective measures have been described to prevent contrast-induced nephropathy (CIN). This study is aimed to evaluate the effect of a high dose of N-acetylcysteine (NAC) plus hydration, a low dose of NAC plus ascorbic acid and hydration or hydration alone on the prevention of CIN in high-risk patients undergoing elective coronary artery intervention. We conducted a randomized, prospective, placebo-controlled trial of 105 high-risk patients undergoing elective cardiac catheterization. The patients were divided into three different groups: Group A (n=30), NAC 1200 mg orally before angiography and 1200 mg orally twice daily for three doses along with good hydration; Group B (n=30), NAC 600 mg before angiography and 600 mg orally twice daily for three doses plus ascorbic acid (3000 mg one dose) before angiography and 2000 mg two doses after angiography and good hydration; and Group C (n=45), hydration with 0.9% saline started just before contrast media injection and continued for 12 h at a rate 1.0 mL/kg//min after angiography or 0.5 mL/kg/h in cases with overt heart failure for 12 h. CIN was defined as an increase in serum creatinine of >25% of baseline or an absolute increase of 0.5 mg/dL above baseline after 48 h. The incidence of CIN was significantly lower in Group A (6.66%) compared with Group B (16.66%) or Group C (17.77%). The difference between Groups A and B and between Groups A and C was also highly significant (P=0.001). In contrast, the difference between Groups B and C was not statistically significant (P=0.37). Our study indicates that high doses of NAC plus hydration provide better protection against CIN than combination therapy of NAC and ascorbic acid plus hydration, or hydration alone.

Topics: Acetylcysteine; Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Cardiac Catheterization; Contrast Media; Coronary Angiography; Creatinine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Kidney Diseases; Male; Middle Aged; Prospective Studies; Treatment Outcome

To determine the incidence of contrast-induced nephropathy (CIN) and to assess the effectiveness of ascorbic acid in the prevention of CIN after coronary angiography in patients with chronic renal impairment. CIN is the third most common cause of hospital-acquired renal failure. It is well documented that periprocedural hydration is effective in the prevention of CIN. Little data exist on the effectiveness of ascorbic acid, a vitamin with antioxidative action. Patients with stable serum creatinine level >107 μmol/L (n = 81) undergoing coronary angiography were randomized to receive either ascorbic acid (N = 40) or placebo (N = 41) before the procedure. All patients received intravenous volume expansion with normal saline before the procedure. CIN was defined as an increase of serum creatinine level >25% from baseline measured 3 to 4 days after the procedure. CIN occurred totally in 5/81 patients (6.2%); in two patients (3%) in the ascorbic acid group and in three patients (7.3%) in the placebo group (P = 0.512). Postprocedural worsening of renal function (postprocedural increase of serum creatinine level) was present in 10/81 patients (12.3%) in the ascorbic acid group and in 19/81 patients (23.4%) in the placebo group (P = 0.038). No patient required dialysis treatment. We found no statistically significant impact of ascorbic acid on the incidence of CIN in patients with chronic renal impairment undergoing coronary arteriography or angioplasty. Ascorbic acid may still have some protective role in CIN reflected in lower incidence of worsening of renal function in the treated group.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Contrast Media; Coronary Angiography; Creatinine; Double-Blind Method; Female; Follow-Up Studies; Humans; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic; Treatment Outcome

Volume supplementation by saline infusion combined with N-acetylcysteine (NAC) represents an effective strategy to prevent contrast agent-induced nephrotoxicity (CIN). Preliminary data support the concept that sodium bicarbonate and ascorbic acid also may be effective in preventing CIN.. Three hundred twenty-six consecutive patients with chronic kidney disease, referred to our institutions for coronary and/or peripheral procedures, were randomly assigned to prophylactic administration of 0.9% saline infusion plus NAC (n=111), sodium bicarbonate infusion plus NAC (n=108), and 0.9% saline plus ascorbic acid plus NAC (n=107). All enrolled patients had serum creatinine > or = 2.0 mg/dL and/or estimated glomerular filtration rate < 40 mL x min(-1) x 1.73 m(-2). Contrast nephropathy risk score was calculated in each patient. In all cases, iodixanol (an iso-osmolar, nonionic contrast agent) was administered. The primary end point was an increase of > or = 25% in the creatinine concentration 48 hours after the procedure (CIN). The amount of contrast media administered (179+/-102, 169+/-92, and 169+/-94 mL, respectively; P=0.69) and risk scores (9.1+/-3.4, 9.5+/-3.6, and 9.3+/-3.6; P=0.21) were similar in the 3 groups. CIN occurred in 11 of 111 patients (9.9%) in the saline plus NAC group, in 2 of 108 (1.9%) in the bicarbonate plus NAC group (P=0.019 by Fisher exact test versus saline plus NAC group), and in 11 of 107 (10.3%) in the saline plus ascorbic acid plus NAC group (P=1.00 versus saline plus NAC group).. The strategy of volume supplementation by sodium bicarbonate plus NAC seems to be superior to the combination of normal saline with NAC alone or with the addition of ascorbic acid in preventing CIN in patients at medium to high risk.

Topics: Acetylcysteine; Administration, Oral; Aged; Ascorbic Acid; Cardiovascular Diseases; Contrast Media; Creatinine; Double-Blind Method; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Kidney Diseases; Male; Renal Insufficiency; Risk Factors; Sodium Bicarbonate; Sodium Chloride; Treatment Outcome; Triiodobenzoic Acids

Contrast-media induced nephropathy (CIN) remains a common complication after contrast dye exposure especially in patients with chronic renal impairment (CRI). We sought to evaluate the efficacy of the antioxidant ascorbic acid as an adjunct to hydration in limiting the incidence of contrast induced nephrotoxicity after coronary procedures.. In a randomized, double-blind, prospective, single center-study, 143 consecutive patients with CRI (creatinine level > 120 micromol/l) referred to coronary angiography/intervention were randomly assigned to receive 1 g ascorbic acid or placebo in adjunct to saline hydration prior to and after angiography. Creatinine and urea nitrogen levels were measured prior to and up to 6 days after exposure to contrast agent.. The development of CIN occurred totally in 8/143 (5.6%) patients. Between the two groups no significant difference was detected (Vitamin C 5/74 (6.8%) patients; placebo 3/69 (4.3%) patients). After adjusting for the amount of contrast dye, drug treatment, cardiovascular risk factors, ejection fraction, or sex, again no differences were detected. No patient required dialysis. More patients with diabetes had development of CIN (7/85; 8.2%) compared with nondiabetic patients (1/58; 1.7%), although not significant (p = 0.14). The incidence of CIN was elevated in patients with high amounts (> 140 ml) of contrast volume used (6/8).. Our study does not support the prophylactic use of ascorbic acid in patients with renal dysfunction exposed to contrast dye.

Topics: Aged; Ascorbic Acid; Contrast Media; Creatinine; Demography; Female; Humans; Incidence; Kidney Diseases; Kidney Function Tests; Male; Treatment Failure

Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated.. We conducted a randomized, double-blind, placebo-controlled trial of ascorbic acid in 231 patients with a serum creatinine concentration > or =1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid, 3 g at least 2 hours before the procedure and 2 g in the night and the morning after the procedure, or placebo was administered orally. Contrast-mediated nephropathy was defined by an absolute increase of serum creatinine > or =0.5 mg/dL or a relative increase of > or =25% measured 2 to 5 days after the procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%) in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85; P=0.02). The mean serum creatinine concentration increased significantly in the placebo group (from 1.36+/-0.50 to 1.50+/-0.54 mg/dL, P<0.001) and nonsignificantly in the ascorbic acid group (from 1.46+/-0.52 to 1.52+/-0.64 mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL; 95% CI, 0.00 to 0.17; P=0.049).. Prophylactic oral administration of ascorbic acid may protect against contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure.

Topics: Acute Kidney Injury; Administration, Oral; Aged; Angioplasty, Balloon, Coronary; Antioxidants; Ascorbic Acid; Contrast Media; Coronary Angiography; Creatinine; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Middle Aged; Osmolar Concentration; Oxidative Stress; Premedication; Risk; Treatment Outcome; Urea

Studies into the functions and mechanisms of action of quercetin may be able to help dispel the negative effects of toxicants on renal toxicity due to its anti-inflammatory potential, as well as provide a simple, low-cost alternative for treating renal toxicity in developing nations. Therefore, the present study evaluated the ameliorative and renal protective activities of quercetin dihydrate in potassium bromate-induced, renal-toxic Wistar rats. Forty-five (45) mature female Wistar rats (180-200 g) were randomly grouped into nine (9) (n = 5). Group A served as general control. Nephrotoxicity was induced in groups B to I with the administration of potassium bromate. While group B served as a negative control, groups C-E received graded doses of quercetin (40, 60, and 80 mg/kg, respectively). Group F received 2.5 mg/kg/day of vitamin C, while groups G-I received vitamin C (2.5 mg/kg/day) and co-administration of a graded dose of quercetin (40, 60, and 80 mg/kg, respectively). Daily urine levels and final blood samples by retro-orbital techniques were collected for GFR, urea, and creatinine level assessment. The collected data were subjected to ANOVA and Tukey's post hoc test, and the results were presented as mean SEM with a p < 0.05 level considered significant. Body and organ weight and GFR were significantly reduced (p < 0.05), while serum and urine creatinine and urea were decreased in renotoxic animals. However, treatment with QCT reversed the renotoxic effects. We, therefore, concluded that quercetin administered alone or with vitamin C conferred renal protection by reversing KBrO

Topics: Animals; Antioxidants; Ascorbic Acid; Creatinine; Female; Flavonoids; Kidney; Kidney Diseases; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Renal Insufficiency; Urea

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Creatinine; Humans; Kidney Diseases; Spectroscopy, Fourier Transform Infrared

Paraquat (PRQ) is a toxic chemical compound that is very noxious to animals and humans. Gallic acid is a phenolic compound that has antioxidant properties. In this study, we evaluated the ameliorative effect of gallic acid against PRQ-induced renal injury and oxidative stress. In this research, the rats were segregated into six groups. Group 1 is the control group; group 2 received paraquat only; group 3 received gallic acid only; and groups 4, 5, and 6 received paraquat plus gallic acid at doses of 25, 50, and 100 mg/kg bw respectively. Findings of this work displayed that the renal contents of the vitamin C, superoxide dismutase (SOD), and catalase (CAT) significantly reduced and the levels of the serum protein carbonyl, creatinine, serum glutamate pyruvate transaminase (sGPT), urea, serum glutamate oxaloacetate transaminase (sGOT), uric acid, MDA, serum IL-1β, and the kidney IL-1β gene expression were remarkably increased in the group receiving PRQ only compared with that in the control group. On the other hand, treatment with gallic acid after exposure to PRQ led to a significant elevation in renal vitamin C, SOD, and CAT levels plus a remarkable decrease in the serum protein carbonyl, creatinine, sGPT, urea, sGOT, uric acid, MDA, IL-1β, and renal gene expression of IL-1β in comparison with the PRQ-only-treated rats. Histological changes were also ameliorated by gallic acid administration. The data approve that gallic acid diminished the deleterious effects of PRQ exposure. In this regard, our results indicated that the administration of gallic acid could alleviate the noxious effects of PRQ on the antioxidant defense system and renal tissue.

Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Catalase; Gallic Acid; Herbicides; Interleukin-1beta; Kidney; Kidney Diseases; Male; Malondialdehyde; Paraquat; Protein Carbonylation; Rats, Wistar; Superoxide Dismutase; Uric Acid

COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure.. A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India.. This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.

Topics: Acute Kidney Injury; Ascorbic Acid; COVID-19; Fatal Outcome; Graft Rejection; Humans; Hyperoxaluria; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Primary Graft Dysfunction

Hyperuricemia contributes to chronic kidney disease development. However, it has been historically viewed with limited research interest. In this study, we mimicked the development of hyperuricemic nephropathy by using a potassium oxonate-induced hyperuricemia rat model. We found that administering vitamin C at 10 mg/kg/day effectively ameliorated hyperuricemic nephropathy. Compared to the control group, rats with hyperuricemia had significantly increased serum uric acid level, xanthine oxidase activity, and urine microalbumin level, by 5-fold, 1.5-fold, and 4-fold, respectively. At the same time, vitamin C supplementation reverted these values by 20% for serum uric acid level and xanthine oxidase activity and 50% for microalbumin level. Vitamin C also alleviated renal pathology and decreased the expression of pro-inflammatory and pro-fibrotic markers. A further mechanistic study suggested that vitamin C might attenuate hyperuricemic nephropathy in renal tubular epithelial cells induced by monosodium urate (MSU) crystal, at least in part, by directly inhibiting IL-6/JAK2/STAT3 signaling pathway. Meanwhile, in macrophages, vitamin C inhibited the expression of TGF-β, and reduced ROS level induced by MSU by about 35%. In short, our results suggest that vitamin C supplementation delay the progression of hyperuricemic nephropathy.

Topics: Animals; Antioxidants; Ascorbic Acid; Fibrosis; Hyperuricemia; Inflammation; Kidney Diseases; Male; Oxonic Acid; Rats; Rats, Sprague-Dawley

Vancomycin is recommended for treating severe infections caused by Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. However, renal damage often occurs as a side effect because vancomycin is mainly excreted via the kidneys. The mechanism of vancomycin-associated nephrotoxicity is thought to involve the elevation of oxidative stress in the kidneys. Vitamin C (VC) has strong antioxidant properties; therefore, we evaluated the effect of high-dose VC preadministration on vancomycin-associated nephrotoxicity. Vancomycin was intraperitoneally injected into mice once daily for 7 d. Additionally, high-dose VC was intraperitoneally injected into mice at 30 min before vancomycin administration for 7 d. The plasma creatinine and urea nitrogen levels were increased by vancomycin treatment; however, high-dose VC preadministration suppressed the increase in these levels. Histological examination also revealed that high-dose VC preadministration reduced the characteristics of vancomycin-associated nephrotoxicity, such as dilated renal tubules with casts, the dilation of renal proximal tubules, and tubular epithelial desquamation. Furthermore, high-dose VC preadministration reduced the appearance of apoptotic cells presumably derived from the epithelial cells in the dilated proximal tubules. Thus, intraperitoneally injected high-dose VC preadministration reduced vancomycin-associated nephrotoxicity in mice. These novel findings may indicate that vancomycin-associated nephrotoxicity in humans may be reduced by high-dose VC preadministration.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Injections, Intraperitoneal; Kidney; Kidney Diseases; Methicillin-Resistant Staphylococcus aureus; Mice; Oxidative Stress; Staphylococcal Infections; Vancomycin

Cisplatin (CDDP) may induce nephrotoxicity through oxidative stress, DNA damage, and inflammation. This study was performed to evaluate the antioxidant and anti-inflammatory effects of allicin and ascorbic acid (AA) and investigate the nephroprotective efficacy of their combination against CDDP-induced intoxication. Rats were divided into seven groups: control, allicin (10 mg/kg for 14 days), AA (20 mg/kg for 14 days), CDDP (7 mg/kg as a single dose on the seventh experimental day), CDDP-allicin, CDDP-AA, and CDDP-allicin-AA (at the aforementioned doses). The administration of CDDP induced marked body weight loss and renal damage, manifested by significant increases (p < 0.05) in serum creatinine, urea, and uric acid levels and significant reductions in serum Na, Ca, and phosphorus concentrations, in addition to severe alterations in serum and renal tissue levels of tumor necrosis factor-α in comparison with control rats. Moreover, CDDP-intoxicated rats exhibited significantly (p < 0.05) higher lipid peroxidation, as well as lower levels of reduced glutathione and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymes in the renal tissue, compared with control rats. The administration of allicin or AA significantly reduced (p < 0.05) the CDDP-induced changes in all the aforementioned parameters. Interestingly, allicin achieved comparable nephroprotection to AA in most assessed parameters; however, the restoration of normal serum and renal tissue concentrations of these parameters was more frequent in the CDDP-AA group. In conclusion, both allicin and AA showed significant nephroprotective effects against CDDP intoxication and their combination exhibited better protection than either agent alone. These results are probably mediated by their antioxidant and anti-inflammatory activities.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Cisplatin; Creatinine; Disulfides; Glutathione; Glutathione Peroxidase; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Rats; Sulfinic Acids; Superoxide Dismutase; Urea

The aim of this study was to verify the protective effects of ascorbic acid (AsA) against lipopolysaccharide (LPS)-induced sepsis. The study was conducted using osteogenic disorder Shionogi (ODS) rats, which are unable to synthesize AsA. Male ODS rats (6 wk old) were fed either an AsA-free diet (AsA-deficient group), a diet supplemented with 300 mg/kg AsA (control group), or a diet supplemented with 3,000 mg/kg AsA (high-AsA group) for 8 d. On day 8, all the rats were intraperitoneally injected with LPS (15 mg/kg body weight). Forty-eight hours after the injection, the survival rates of the rats in the control (39%) and the high-AsA (61%) groups were significantly higher than that in the AsA-deficient group (5.5%). Next, we measured several inflammatory parameters during 10 h after administering LPS. At 6 h, elevated serum levels of markers for hepatic and systemic injuries were suppressed in rats fed AsA. Similarly, 10 h after LPS injection, the elevation in the serum levels of markers for renal injury were also suppressed proportionally to the amount of AsA in the diet. The elevated serum concentrations of TNFα and IL-1β by LPS in the AsA-deficient group decreased in groups fed AsA. Hematic TNFα mRNA levels at 6 h after the LPS injection were also lowered by feeding AsA. These results demonstrated that the dietary intake of AsA improved the survival rates and suppressed the inflammatory damage, in a dose-dependent manner, caused during sepsis induced by LPS in ODS rats.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Supplements; Inflammation; Interleukin-1beta; Kidney; Kidney Diseases; Lipopolysaccharides; Liver; Liver Diseases; Male; Nutritional Status; Osteogenesis; Rats; Rats, Inbred Strains; Sepsis; Tumor Necrosis Factor-alpha; Vitamins

This study was to determine the impact of maternal exposure to di-n-butyl phthalate (DBP) on renal development and fibrosis in adult offspring. Pregnant rats received DBP at a dose of 850 mg/kg BW/day by oral perfusion during gestational days 14-18. In DBP exposed newborn offspring, gross observation and histopathological examination revealed the dysplasia of kidney. The expression of genes related to renal development was also changed. In DBP exposed adult offspring, histopathological examination and Masson's trichrome staining revealed the pathological changes of renal fibrosis. Furthermore, higher expression levels of transforming growth factor- β (TGF-β) and alpha-smooth muscle actin (α-SMA) were also detected. In vitro studies reveal that DBP promoted the activation of NRK49F cells and G2/M arrest in NRK52E cells at a sublethal dose. The effect of DBP on these cell lines was linked to the generation of oxidative stress. In addition, DBP induced oxidative stress in both renal fibroblasts and tubular epithelial cells, whereas vitamin C ameliorated the changes caused by DBP. In conclusion, our results showed that prenatal exposure to DBP may generate oxidative stress in both renal fibroblasts and tubular epithelial cells, leading to kidney dysplasia and renal fibrosis.

Topics: Animals; Apoptosis; Ascorbic Acid; Cell Proliferation; Dibutyl Phthalate; Disease Models, Animal; Endocrine Disruptors; Female; Fibrosis; G2 Phase Cell Cycle Checkpoints; Kidney Diseases; Maternal Exposure; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Transforming Growth Factor beta

Vitamin C may reduce inflammation and is inversely associated with mortality in the general population. We investigated the association of plasma vitamin C with all-cause mortality in renal transplant recipients (RTR); and whether this association would be mediated by inflammatory biomarkers. Vitamin C, high sensitive C-reactive protein (hs-CRP), soluble intercellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured in a cohort of 598 RTR. Cox regression analyses were used to analyze the association between vitamin C depletion (≤28 µmol/L; 22% of RTR) and mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. At a median follow-up of 7.0 (6.2-7.5) years, 131 (21%) patients died. Vitamin C depletion was univariately associated with almost two-fold higher risk of mortality (Hazard ratio (HR) 1.95; 95% confidence interval (95%CI) 1.35-2.81,

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Creatinine; Dietary Supplements; Endpoint Determination; Female; Follow-Up Studies; Humans; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Proteinuria; Vascular Cell Adhesion Molecule-1

Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.. Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.. The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.. Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Topics: Acetaminophen; Analgesics; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cytokines; Dinoprost; Inflammation; Interleukin-1beta; Kidney Diseases; Lipid Peroxidation; Male; Oxidative Stress; Platelet Activation; Rats; Rats, Wistar; Thromboxane B2; Tumor Necrosis Factor-alpha

Cisplatin (CP) has been used to cure numerous forms of cancers effectively in clinics, however, it could induce some toxic effects. Bee pollen is a natural compound, produced by honey bees. It is obtained from collected flower pollen and nectar, mixed with bee saliva. Bee pollen produced from Schisandra chinensis plants is described to exert potent antioxidant effects and to be a free radical scavenger. The purpose of this study was to investigate the effects of therapeutic treatment with Schisandra chinensis bee pollen extract (SCBPE) on liver and kidney injury induced by CP. The rats were intragastrically administrated with different doses of SCBPE (400mg/kg/day, 800mg/kg/day, 1200mg/kg/day) and vitamin C (400mg/kg/day, positive control group) for 12days, and the liver and kidney injury models were established by single intraperitoneal injection of CP (8mg/kg) at seventh day. The effect of SCBPE on CP toxicity was evaluated by measuring markers of liver and kidney injury in serum, levels of lipid peroxidation and antioxidants in liver and kidney, observing pathological changes of tissue, and quantified expression of NFκB, IL-1β, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney. Compared with the model group, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the content of blood urea nitrogen (BUN), creatinine (Cr) in serum all decreased in SCBPE high dose group. Meanwhile, the activities of superoxide dismutase (SOD), catalase (CAT) and the content of reduced glutathione (GSH) in liver and kidney increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that the pathological changes of liver and kidney were found in the model group, and SCBPE group reduced to varying degrees. Moreover, the expression of NFκB, IL-1β, IL-6, cytochrome C, caspase3, caspase9, p53 and Bax in liver and kidney decreased. Therefore, SCBPE could reduce the damage of liver and kidney caused by CP by reducing the level of oxidative stress, and improving the antioxidant, anti-inflammatory and anti-apoptotic capacity of the body.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Bees; Chemical and Drug Induced Liver Injury; Cisplatin; Dose-Response Relationship, Drug; Free Radical Scavengers; Kidney Diseases; Lipid Peroxidation; Male; Malondialdehyde; Oxidative Stress; Pollen; Rats; Rats, Sprague-Dawley; Schisandra

To report a case of acute oxalate nephropathy related to vitamin C intake within the intensive care unit (ICU).. Case report.. ICU and nephrology department of a French university hospital.. A 57-year-old woman with septic shock related to Legionella pneumophila pneumonia complicated by acute respiratory distress syndrome and acute kidney injury who required renal replacement therapy for 75 days.. A renal biopsy was performed on day 72 because of persistent anuria and because the patient showed characteristic features of severe acute oxalate nephropathy. The only cause identified was vitamin C intake received during hospitalization within the ICU (~ 30 g over 2.5 months). At month 6 after ICU admission, estimated glomerular filtration rate was 24 mL/min/1.73m. Compelling evidence obtained from in-vitro and animal studies suggest that vitamin C, a circulating antioxidant, may be a valuable adjunctive therapy in critically-ill patients. Data from humans are more conflicting. Oxalate, a well-known metabolite of vitamin C, is excreted by the kidneys and can exert a toxic effect on epithelial cells and causes direct tubular damage, and/or it can crystallize within the tubular lumen. This case highlights an under-recognized secondary adverse event from vitamin C given to critically-ill patients. The use of high-dose vitamin C should be prescribed with caution in this population.
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Topics: Acute Kidney Injury; Ascorbic Acid; Critical Illness; Female; Humans; Intensive Care Units; Kidney Diseases; Middle Aged; Oxalates; Renal Replacement Therapy

Topics: Anti-Bacterial Agents; Ascorbic Acid; Colistin; Humans; Kidney; Kidney Diseases

Endosulfan is an insecticide that is composed of two stereoisomers: α- and β- endosulfan in an approximate ratio of 70:30. Owing to its widespread use, poisoning of both humans and animals is possible. We examined the toxic effects of endosulfan on New Zealand white rabbit kidneys. Rabbit kidneys were examined histopathologically and caspase-3 activity was detected using immunohistochemistry. Animals were divided into four groups: Group 1 was given a sublethal dose of endosulfan in corn oil by oral gavage daily for 6 weeks, Group 2 was given endosulfan + vitamin C during the same period, Group 3 was given corn oil daily and vitamin C on alternate days, Group 4 was given only corn oil daily throughout the experiment. By the end of experimental period, the concentration of α-endosulfan was greater than the β-endosulfan concentration in the kidneys of both of endosulfan treated groups (Groups 1 and 2). Decreased accumulation of α- and β-endosulfan was observed in Group 2, possibly because of the antioxidant effect of the vitamin C. Histopathological examination revealed hemorrhages, tubule cell necrosis, glomerular infiltration, glomerulosclerosis and proteinaceous material in the tubules, and Bowman spaces in the kidneys of Group 1. Caspase-3 reaction was stronger in Group 1 than in the other groups. Apoptotic activity was most frequent in proximal tubule cells. Endosulfan is toxic to rabbit kidneys. Vitamin C treatment reduced the accumulation of endosulfan in kidneys and reduced its toxicity.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Caspase 3; Endosulfan; Insecticides; Kidney; Kidney Diseases; Male; Necrosis; Rabbits

Deltamethrin (DLM) is a synthetic class II pyrethroid acaricide and insecticide widely used for veterinary and agricultural purposes. However, its animal and human exposure leads to nephrotoxicity. Our experimental objective was to evaluate protective effects of ceftriaxone and/or ascorbic acid against DLM-induced renal injury in male Wistar albino rats. DLM-treated animals revealed significant alterations in serum biochemical parameters related to renal injury; urea, uric acid and creatinine. There was a significant increase in renal lipid peroxidation and a significant inhibition in antioxidant biomarkers. Moreover, DLM significantly reduced serum acetylcholinesterase (AChE) activity. In addition, It induced serum and kidney tumor necrosis factor-α (TNF-α). Both ceftriaxone and ascorbic acid protect against DLM-induced biochemical alterations in serum and renal tissue when used alone or in combination along with DLM-intoxication. Furthermore, both ceftriaxone and ascorbic acid produced synergetic nephroprotective and antioxidant effects. Therefore, it could be concluded that ceftriaxone and/or ascorbic acid administration able to minimize the toxic effects of DLM through their free radical-scavenging and potent antioxidant activity.

Topics: Acetylcholinesterase; Animals; Antioxidants; Ascorbic Acid; Ceftriaxone; Creatinine; Disease Models, Animal; Insecticides; Kidney Diseases; Lipid Peroxidation; Male; Nitriles; Oxidative Stress; Protective Agents; Pyrethrins; Rats; Rats, Wistar; Treatment Outcome; Tumor Necrosis Factor-alpha; Uric Acid

To compare the protective efficacy of erdosteine and vitamins C and E against renal injury caused by hind limb ischemia-reperfusion (I/R).. Rats were split into 4 groups: group I as the control, group II as I/R, group III as I/R + erdosteine, and group IV as I/R + vitamins C and E. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA) tissue levels were determined.. MDA levels were found comparable with the control group in groups II and III. However, they were considerably decreased in group IV when compared to group II (P < 0.01). Additionally, SOD, CAT, and GSH-Px activities were considerably (P < 0.05) decreased in group II. While CAT and GSH-Px activities were restored (P <0.01) by vitamin E and C treatment, SOD activity was not significantly affected. While GSH-Px activities were higher (P < 0.05) with erdosteine administration, SOD and CAT activities were unchanged.. The protective effect of vitamins C and E is higher than that of erdosteine treatment in reducing the oxidative stress after renal ischemia in this animal model.

Topics: Animals; Antioxidants; Ascorbic Acid; Hindlimb; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Oxidoreductases; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Thioglycolates; Thiophenes; Vitamin E

Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AA‑induced cytotoxicity is associated with increases in oxidative stress and caspase‑3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspase‑dependent and ‑independent pathways. It is desirable to identify means of inhibiting AA‑induced renal damage; therefore, the present study applied an anti‑oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA‑induced cell cytotoxicity. The results showed that vitamin C decreased AA‑induced H2O2 levels, caspase‑3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA‑induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase‑dependent and ‑independent pathways, and that vitamin C can decrease AA‑induced increases in H2O2 levels and caspase‑3 activity to attenuate AA‑induced cell cytotoxicity.

Topics: Animals; Apoptosis; Aristolochia; Aristolochic Acids; Asarum; Ascorbic Acid; Caspase 3; Cell Line; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Hydrogen Peroxide; Kidney Diseases; Kidney Tubules; Oxidative Stress; Rats

CV247 (CV), an aqueous mixture of copper (Cu) and manganese (Mn) gluconates, vitamin C and sodium salicylate increased the antitumour effects of cisplatin (CDPP; cis-diamminedichloroplatinum) in vitro. We hypothesized that the antioxidant and cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2) inhibitory components of CV can protect the kidneys from CDPP nephrotoxicity in rats. CDPP (6.5 mg/kg, intraperitoneally) slightly elevated serum creatinine (Crea) and blood urea nitrogen (BUN) 12 days after treatment. Kidney histology demonstrated extensive tubular epithelial damage and COX-2 immunoreactivity increased 14 days after treatment. A large amount of platinum (Pt) accumulated in the kidney of CDPP-treated rats. Furthermore, CDPP decreased renal iron (Fe), molybdenum (Mo), zinc (Zn), Cu and Mn concentrations and increased plasma Fe and Cu concentrations. CDPP elevated plasma free radical concentration. Treatment with CV alone for 14 days (twice 3 ml/kg/day orally) did not influence these parameters. Chronic CV administration after CDPP reduced renal histological damage and slightly decreased COX-2 immunoreactivity, while failed to prevent the increase in Crea and BUN levels. Blood free radical concentration was reduced, that is, CV improved redox homeostasis. CV restored plasma Fe and renal Fe, Mo and Zn, while decreased Pt and elevated Cu and Mn concentrations in the kidney. Besides the known synergistic antitumour effects with CDPP, CV partially protected the kidneys from CDPP nephrotoxicity probably through its antioxidant effect.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Blood Urea Nitrogen; Cisplatin; Creatinine; Cyclooxygenase 2; Cytoprotection; Disease Models, Animal; Gluconates; Kidney; Kidney Diseases; Male; Metals; Oxidation-Reduction; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Sodium Salicylate; Time Factors

In response to sustained damage to a kidney, fibrosis that can be characterized as the deposition of a collagenous matrix occurs and consequently causes chronic kidney failure. Because most animals used in experiments synthesize ascorbic acid (AsA) from glucose, the roles of AsA in fibrotic kidney diseases are largely unknown. Unilateral ureteric obstruction (UUO) mimics the complex pathophysiology of chronic obstructive nephropathy and is an ideal model for the investigation of the roles of AsA in kidney failure. We examined the impact of a deficiency of Akr1a, a gene that encodes aldehyde reductase and is responsible for the production of AsA, on fibrotic damage caused by UUO in mice. Oxidatively modified DNA was elevated in wild-type and Akr1a-deficient kidneys as a result of UUO to a similar extent, and was only slightly suppressed by the administration of AsA. Even though Akrla-deficient mice could produce only about 10% of the AsA produced by wild-type mice, no difference was observed in collagen I synthesis under pathological conditions. The data implied either a low demand for AsA or the presence of another electron donor for collagen I production in the mouse kidney. Next, we attempted to elucidate the potential causes for oxidative damage in kidney cells during the fibrotic change. We found decreases in mitochondrial proteins, particularly in electron transport complexes, at the initial stage of the kidney fibrosis. The data imply that a dysfunction of the mitochondria leads to an elevation of ROS, which results in kidney fibrosis by stimulating cellular transformation to myofibroblasts.

Topics: Animals; Ascorbic Acid; Blotting, Western; Disease Models, Animal; Electron Transport Chain Complex Proteins; Fibrosis; Immunohistochemistry; Kidney Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Ureteral Obstruction

Vitamin C (vit C) has been shown to diminish cisplatin (CP)-induced nephrotoxicity and oxidative damage in healthy rats and mice. However, little is known whether vit C has similar actions and enhances the anticancer effect of CP in tumor-bearing mice. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before intraperitoneal administration with CP (5 mg/kg) in the presence or absence of low- (200 mg/kg) and high- (1000 mg/kg) dose vit C twice a week for an additional 28 days. Results reveal that vit C or CP treatment alone significantly inhibited tumor growth, although vit C in combination with CP did not further inhibit tumor growth, as compared to CP treatment alone. In addition, CP significantly induced nephrotoxicity and oxidative damage, as evidenced by increased plasma levels of blood urea nitrogen and creatinine as well as levels of lipid peroxidation and carbonyls, decreased ratios of GSH/GSSG in liver and kidney. Vit C significantly reversed these undesirable side effects induced by CP, and most of these actions of vit C were dose-dependent. Overall, we conclude that vit C can protect against CP-induced nephrotoxicity and damage without reducing CP's effectiveness in LLC-bearing mice.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Blood Urea Nitrogen; Carcinoma, Lewis Lung; Cell Line, Tumor; Cisplatin; Creatinine; Glutathione; Kidney; Kidney Diseases; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Protein Carbonylation; Xenograft Model Antitumor Assays

Ascorbic acid (AA) is a naturally occurring organic compound with antioxidant properties. It is necessary for normal growth and development, and has been shown to protect against tissue toxicity and oxidative stress.. The protective effect of AA against nephrotoxicity induced in albino rats by ferric nitrilotriacetate (Fe-NTA) was evaluated.. Male albino rats of Wistar strain (4-6 weeks old) weighing 125-150 g were used in this study. Animals were given a single dose of Fe-NTA (9 mg/kg body weight, intraperitoneal) after a week of treatment with AA (1 and 2 mg/animal/day).. Fe-NTA treatment enhanced microsomal lipid peroxidation (LPO) and hydrogen peroxide (H2O2) generation to 1.7- to 2.2-fold, glutathione (GSH) levels were decreased by two-fold and the activities of GSH metabolizing enzymes decreased to a range of 2.2- to 2.5-fold in renal tissue. These changes were reversed significantly in animals receiving pretreatment of AA. Treatment of rats with AA prior to the treatment with Fe-NTA decreased microsomal LPO and H2O2 generation to 124 and 172%, and also resulted in the recovery of reduced levels of GSH, GSH-metabolizing enzymes to almost 92% at the higher dose level of AA.. AA protects against Fe-NTA-induced nephrotoxicity and renal damage. AA has a beneficial impact on Fe-NTA-induced toxicity due to its scavenging and antioxidant effect in albino rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Ferric Compounds; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Kidney Diseases; Lipid Peroxidation; Male; Microsomes; Nitrilotriacetic Acid; Oxidative Stress; Rats; Rats, Wistar

Clinically, chronic nephrotoxicity may lead to renal functional impairment and progress to end stage renal failure. The renoprotective effect of a flavonoid naringin (NG) against cyclosporine A (CsA)-induced nephrotoxicitywas investigated in this study.. Nephrotoxicity was induced in male albino Wistar rats by injecting 25 mg/kg body weight of CsAfor a period of 21 days. CsA-induced rats were also cotreated with 40 mg of NG/kg body weight, orally.. After the experimental period, the levels of lipid peroxides (TBARS) and hydroxyl radical (OH·) were found to be elevated, whereas the levels of SOD, catalase, glutathione, vitamin C, E and A were decreased in CsA-induced rats. NG co-treatment significantly decreased the levels of lipid peroxides and hydroxyl radicals and restored the levels of enzymic and non-enzymic antioxidants in renal tissues. Histological analysis revealed that CsA administration caused severe and widespread necrosis with dilatation of proximal tubules, vacuolization, tubular cell desquamation and intraluminal cast formation with massive infiltration of inflammatory cells. CsA-induced histopathological renal changes were minimal in animals which received NG treatment. The western blot and confocal microscopic expression of heme oxygenase-1 was restored by NG. In CsA-induced animals the expression was reduced compared to NG treated animals.. The present study reveals that NG can act as effective renoprotective drug against CsA-induced toxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Cyclosporine; Cytoprotection; Disease Models, Animal; Flavanones; Heme Oxygenase (Decyclizing); Hydroxyl Radical; Kidney; Kidney Diseases; Male; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin A; Vitamin E

Organoselenium compounds have important pharmacological properties. However, these compounds can cause toxicity, typically related to oxidation of endogenous thiols. The aim of this study was to investigate whether 2,2'-dithienyl diselenide (DTDS) has potential toxicity in vitro and in vivo. Therefore, sulfhydryl-containing enzyme activities, δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na(+) -K(+) -ATPase were used to predict DTDS toxicity in rat brain homogenate in vitro. In in vivo experiments, a DTDS administration (50 or 100 mg kg(-1) , p.o.) to rats was performed and toxicological parameters were determined. DTDS inhibited δ-ALA-D (IC50 2 µm) and Na(+) -K(+) -ATPase (IC50 17 µm) activities in vitro. The inhibitory effect of DTDS on δ-ALA-D and Na(+) -K(+) -ATPase activities was restored by dithiothreitol. DTDS (5-25 µm) elicited a thiol oxidase-like activity. In vivo, DTDS (50 and 100 mg kg(-1) ) caused systemic toxicity, evidenced by a decrease in water and food intakes and body weight gain, as well as the death of rats. DTDS at the dose of 100 mg kg(-1) increased plasma alanine and aspartate aminotransferase activities and decreased urea levels. At 50 and 100 mg kg(-1) , it increased lipid peroxidation levels. At the highest dose, DTDS inhibited δ-ALA-D activity. By contrast, Na(+) -K(+) -ATPase activity and antioxidant defense were not altered in the brains of rats exposed to DTDS. In conclusion, interaction with the cisteinyl residues seems to mediate the inhibitory effect of DTDS on sulfhydryl-containing enzymes in vitro. In addition, high oral doses of DTDS induce toxicity in rats.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Catalase; Chemical and Drug Induced Liver Injury; Chlorides; Drinking; Eating; Enzyme Inhibitors; Female; Glutathione; Kidney Diseases; Lipid Peroxidation; Male; Organoselenium Compounds; Oxidoreductases Acting on Sulfur Group Donors; Porphobilinogen Synthase; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase; Thiophenes; Weight Gain; Zinc Compounds

The present study aims to determine the potential of melatonin supplementation in ameliorating tissue oxidative stress, elevated serum corticosterone and hepatic and renal dysfunction.. Adult Wistar rats, either ovariectomized or sham-operated, served as experimental or control groups, respectively. Rats received either melatonin, estrogen, progesterone or a combination of melatonin and estrogen for a period of 15 days. Tissue oxidative stress, serum markers of hepatic and renal dysfunction and serum corticosterone level formed the parameters of assay in all groups at the end of the treatment schedule.. Ovariectomized rats showed significant increases in levels of tissue lipid peroxidation, serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, acid phosphatase and corticosterone and significant decrement in enzymatic and non-enzymatic antioxidant status. All parameters showed maximal reversal to control levels on supplementation with high-dose melatonin or estrogen + melatonin treatment.. Melatonin supplementation proved better than estrogen replacement therapy, with the higher dose being more effective in preventing ovariectomy-induced increases in oxidative stress and serum levels of marker parameters of hepatic and renal dysfunction and corticosterone titer. Overall, melatonin supplementation therapy qualifies as a more potent and safe alternative to estrogen replacement therapy in alleviating postmenopausal increases in oxidative stress and hepatic and renal dysfunction.

Topics: Animals; Ascorbic Acid; Catalase; Corticosterone; Estrogen Replacement Therapy; Estrogens; Female; Glutathione; Glutathione Peroxidase; Kidney Diseases; Lipid Peroxidation; Liver Diseases; Melatonin; Ovariectomy; Oxidative Stress; Progesterone; Rats; Rats, Wistar; Superoxide Dismutase

Gentamicin and vitamin C have been proposed as nephrotoxic and antioxidant, respectively. This study involved biochemical and histopathologic investigation showing protection and treatment of gentamicin-induced nephrotoxicity in rabbits using vitamin C for 26 days hypothesizing that whether vitamin C would inhibit or decrease the raised serum urea and creatinine levels. This study was conducted on 25 healthy male albino rabbits (average weight 1.5±0.2 kg), classified into 5 groups: group A, B, C, D and E for nephrocurative (study-I) and nephroprotective (study-II) studies. Control group of rabbits (group A) received only the vehicle of gentamicin ampoule. In study-I, gentamicin sulphate (GS 80 mg/kg, i.m.) was administered to group B and C rabbits for ten days, then group C rabbits received vitamin C 250 mg/Kg for remaining 16 days. Group D and E received GS 80 mg/kg and GS 80 mg/kg i.m.-vitamin C 250 mg/kg orally, respectively during whole period (26 days) of study-II. After 26 days, various biochemical parameters, i.e. serum creatinine, blood urea nitrogen (BUN), and serum antioxidant activity, and histopathologic investigations were made. Nephrotoxicity was observed in rabbit groups B, C and D as evident from significant (p<0.05) high levels of serum creatinine and BUN and low serum antioxidant levels as compared to the levels of control group. Decrease in the levels of serum creatinine and BUN along with the increase in serum antioxidant activity was observed after vitamin C treatment in group C. While, renal-protective role of vitamin C was seen in group E as compared to the control. In conclusion, Gentamicin induced nephrotoxicity can be attenuated or treated using vitamin C.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Creatinine; Gentamicins; Kidney; Kidney Diseases; Male; Rabbits; Urea; Vitamins

The use of colistin in the treatment of life-threatening Gram-negative infections is associated with a high rate of nephrotoxicity that is dose limiting. This study aimed to examine the nephroprotective effect of ascorbic acid against colistin-induced nephrotoxicity.. Rats were treated intravenously twice daily with saline, colistin (cumulative dose of 36.5 mg/kg), a combination of ascorbic acid (50 or 200 mg/kg) and colistin, or ascorbic acid (200 mg/kg) over 7 days. Colistin-induced apoptosis was examined in rats over 5 days and in vitro using rat renal proximal tubular cells NRK-52E over 24 h with and without ascorbic acid. The effect of co-administered ascorbic acid on colistin pharmacokinetics was investigated.. The 24 h urinary excretion of N-acetyl-β-D-glucosaminidase, a sensitive marker for tubular damage, was significantly lower (P < 0.0001) in the colistin/ascorbic acid 200 mg/kg group. Significant histological abnormalities (P < 0.01) were detected only in the kidneys of the colistin group, which also had the highest percentage (30.6 ± 7.8%) of apoptotic cells (P < 0.005). In the cell culture studies, the percentage of apoptotic cells was significantly higher in the presence of 0.1 mM colistin alone (51.8 ± 2.0%; P < 0.0001) than in the presence of ascorbic acid, which decreased the apoptotic effect in a concentration-dependent manner. Ascorbic acid (200 mg/kg) altered colistin pharmacokinetics, as the total body clearance decreased from 3.78 ± 0.36 mL/min/kg (colistin group) to 2.46 ± 0.57 mL/min/kg (P = 0.0024).. This is the first study demonstrating the protective effect of ascorbic acid against colistin-induced nephrotoxicity and tubular apoptosis. Co-administration of ascorbic acid has the potential to increase the therapeutic index of colistin.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Ascorbic Acid; Cells, Cultured; Colistin; Injections, Intravenous; Kidney Diseases; Male; Rats; Rats, Sprague-Dawley; Vitamins

We investigated whether cosupplementation with synthetic tetra-tert-butyl bisphenol (BP) and vitamin C (Vit C) ameliorated oxidative stress and acute kidney injury (AKI) in an animal model of acute rhabdomyolysis (RM). Rats were divided into groups: Sham and Control (normal chow), and BP (receiving 0.12% w/w BP in the diet; 4 weeks) with or without Vit C (100mg/kg ascorbate in PBS ip at 72, 48, and 24h before RM induction). All animals (except the Sham) were treated with 50% v/v glycerol/PBS (6 mL/kg injected into the hind leg) to induce RM. After 24h, urine, plasma, kidneys, and aortae were harvested. Lipid oxidation (assessed as cholesteryl ester hydroperoxides and hydroxides and F(2)-isoprostanes accumulation) increased in the kidney and plasma and this was coupled with decreased aortic levels of cyclic guanylylmonophosphate (cGMP). In renal tissues, RM stimulated glutathione peroxidase (GPx)-4, superoxide dismutase (SOD)-1/2 and nuclear factor kappa-beta (NFκβ) gene expression and promoted AKI as judged by formation of tubular casts, damaged epithelia, and increased urinary levels of total protein, kidney-injury molecule-1 (KIM-1), and clusterin. Supplementation with BP±Vit C inhibited the two indices of lipid oxidation, down-regulated GPx-4, SOD1/2, and NF-κβ gene responses and restored aortic cGMP, yet renal dysfunction and altered kidney morphology persisted. By contrast, supplementation with Vit C alone inhibited oxidative stress and diminished cast formation and proteinuria, while other plasma and urinary markers of AKI remained elevated. These data indicate that lipid- and water-soluble antioxidants may differ in terms of their therapeutic impact on RM-induced renal dysfunction.

Topics: Animals; Ascorbic Acid; Base Sequence; Biomarkers; Blood Vessels; DNA Primers; Kidney Diseases; Lipids; Male; Models, Animal; Oxidative Stress; Polyphenols; Rats; Rats, Wistar; Rhabdomyolysis

The nephroprotective effect of co-administration of vitamin C and losartan as prophylaxis against cisplatin-induced nephrotoxicity (CIN) was evaluated.. Co-administration of vitamin C and losartan was compared with losartan (10 mg/kg), vitamin C (250 mg/kg), and placebo in 4 groups of rats with CIN. The prophylactic agents were injected daily for a period of 4 days, and on day 3, a single dose (6 mg/kg) of cisplatin was administrated. The animals were sacrificed 7 days later for pathological examination of the kidneys.. Cisplatin prevented the animals' weight gain. The serum levels of creatinine and blood urea nitrogen increased within the groups with CIN, but no significant difference was observed between the groups. The prophylaxis has no effect on serum osmolality, total protein, or nitrite concentrations. The kidney tissue damage was scored, and losartan provided a lower damage score than vitamin C and a combination of vitamin C and losartan.. We concluded that co-administration of vitamin C and losartan was not more effective than the administration of vitamin C or losartan alone.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antioxidants; Ascorbic Acid; Biomarkers; Blood Proteins; Blood Urea Nitrogen; Cisplatin; Creatinine; Cytoprotection; Disease Models, Animal; Drug Therapy, Combination; Kidney; Kidney Diseases; Losartan; Male; Nitrites; Rats; Rats, Wistar; Time Factors; Weight Gain

Oxidative stress causes the generation of reactive oxygen species (ROS) that lead to nephrotoxicity. An aminoglycoside, gentamicin, has pronounced nephrotoxic effect in humans and animals and this study was planned to observe the nephro-protective effect of antioxidants, vitamin C and Nigella sativa oil. Serum creatinine, blood urea nitrogen, and antioxidant activity were measured as indicators of nephrotoxicity for all the groups of rabbits. Results showed that vitamin C and Nigella sativa oil both had nephro-protective effect as they lowered the values of nephrotoxicity indicators (serum creatinine, blood urea nitrogen, and antioxidant activity) as compared to gentamicin control group values. When these two antioxidants were given as combination, they proved to have synergistic nephro-protective effect.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Blood Urea Nitrogen; Creatinine; Cytoprotection; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Gentamicins; Kidney Diseases; Male; Nephrons; Oxidative Stress; Plant Oils; Rabbits; Time Factors

Malakoplakia is an inflammatory granulomatous disease induced by defective phagocytic activity of macrophage. Malakoplakia is histologically characterized by the presence of Michaelis-Gutmann bodies in macrophages. Although not uncommon in the genito-urinary tract, isolated malakoplakia of the kidney is rarely found. Its main clinical presentation associates acute renal failure and acute pyelonephritis. The clue for diagnosis of renal malakoplakia is based on renal biopsy showing Michaelis-Gutmann bodies. Establishing the diagnosis of renal malakoplakia is essential as it determines the choice of antibiotics and duration of treatment. Prognosis remains poor, leading frequently to chronic renal failure. In this paper, we report four cases of renal malakoplakia and discuss clinical presentation, biological and pathological features, treatment and prognosis of this disease.

Topics: Aged; Anti-Bacterial Agents; Ascorbic Acid; Biopsy; Diabetic Nephropathies; Drug Therapy, Combination; Fatal Outcome; Female; Glucocorticoids; Humans; Kidney Diseases; Liver Cirrhosis; Macrophages; Malacoplakia; Male; Middle Aged; Renal Dialysis; Renal Insufficiency; Risk Factors; Treatment Outcome; Vitamins

Acute kidney injury (AKI) occurs frequently in the intensive care unit. A primary cause is renal ischemia/reperfusion (I/R) injury, during which excess reactive oxygen species (ROS) are produced. ROS subsequently damage renal cells, leading to the development of AKI. Here, we investigated whether renal I/R injury could be attenuated by the antioxidant EPC-K1.. We divided male Wistar rats into the following three groups: (1) a renal I/R group, (2) an EPC-K1 + renal I/R group and (3) a control group. Rats were sacrificed 24 h after treatment (I/R or sham). To measure oxidative stress in renal tissue, histological examinations were performed and serum levels of blood urea nitrogen (BUN) and creatinine were measured. The antioxidant action of EPC-K1 was also evaluated in RAW264.7 cells stimulated with antimycin A.. Serum BUN and creatinine levels were elevated in the I/R group; however, this increase was significantly attenuated by EPC-K1 in the EPC-K1 + I/R group. Renal tissue injury was also significantly lower in the EPC-K1 + I/R group compared with the I/R group. In vitro experiments showed that EPC-K1 significantly attenuated the generation of ROS induced by antimycin A.. In our study, EPC-K1 was able to attenuate AKI due to renal I/R by reducing oxidative stress. These results suggest that EPC-K1 may be effective against various types of I/R injury.

Topics: Animals; Antioxidants; Ascorbic Acid; Biomarkers; Cell Line; Disease Models, Animal; Kidney; Kidney Diseases; Kidney Function Tests; Male; Malondialdehyde; Mice; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Vitamin E

The protective effects of an antioxidant combination in kidney injury induced by the injection of D-galactosamine (D-GaIN) were examined in the present study. Sprague Dawley female rats were used and divided into four groups as follows: (1) animals injected physiological saline solution, intraperitoneally, (2) animals treated with the combination of ascorbic acid (100 mg kg(-1) day(-1)), beta-carotene (15 mg kg(-1) day(-1)), alpha-tocopherol (100 mg kg(-1) day(-1)), and sodium selenate (0.2 mg kg(-1) day(-1)) for three days orally, (3) rats injected D-GaIN (500 mg kg(-1)) intraperitoneally as a single dose, and (4) animals treated with the antioxidant combination for three days, then injected D-GaIN. The tissue and blood samples of animals were collected for morphological and biochemical evaluations. Histopathological injury in kidney tissues was observed together with a significant increase in tissue lipid peroxidation (LPO) level, myeloperoxidase (MPO), lactate dehydrogenase, catalase and superoxide dismutase (SOD) activities, and serum creatinine and urea levels, and a significant decrease in glutathione level and glutathione peroxidase activity in D-GaIN injected rats. However, a decrease in the degenerative changes was detected in the kidney tissue of D-GaIN + antioxidant group, and biochemical results showed reversed effects. In conclusion, it seems reasonable to conclude that the treatment of the antioxidant combination has a protective effect on D-GaIN-induced kidney injury of rats.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Creatinine; Female; Galactosamine; Glutathione; Kidney Diseases; Lactate Dehydrogenases; Lipid Peroxidation; Peroxidase; Rats; Rats, Sprague-Dawley; Selenic Acid; Selenium Compounds; Superoxide Dismutase; Urea

The aim of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on antioxidant status and organ damage markers in experimentally-induced endotoxemia. Rats were divided into three groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The two other groups received the following drugs (simultaneously with LPS): ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24 and 48 h. Oxidative stress parameters were determined by ELISA, while serum organ damage markers were measured by autoanalyser. LSP increased (p < 0.05) malondialdehyde, 13,14-dihydro-15-keto-prostaglandin F(2 alpha) and nitric oxide, while LPS reduced vitamin C. These changes were especially inhibited (p < 0.05) by ENR + FM + high-dose DEX. LPS increased organ damages markers. Cardiac and hepatic damage was not completely inhibited by any treatment, whereas renal damage was inhibited by two treatments. This study suggested that ENR + FM + high-dose DEX is most effective in the LPS-caused oxidative stress and organ damages.

Topics: Animals; Ascorbic Acid; Autoanalysis; Biomarkers; Clonixin; Dexamethasone; Dinoprost; Disease Models, Animal; Drug Therapy, Combination; Enrofloxacin; Enzyme-Linked Immunosorbent Assay; Female; Fluoroquinolones; Heart Diseases; Kidney Diseases; Lipopolysaccharides; Liver Diseases; Male; Malondialdehyde; Multiple Organ Failure; Nitric Oxide; Oxidative Stress; Rats; Rats, Sprague-Dawley; Shock, Septic; Superoxide Dismutase; Time Factors

In fawn-hooded hypertensive (FHH) rats, a model of hypertension, impaired preglomerular resistance, hyperfiltration, and progressive renal injury, we recently observed that supporting perinatal nitric oxide (NO) availability with the NO donor molsidomine persistently reduced blood pressure (BP) and ameliorated renal injury in male and female offspring. However, beneficial effects of perinatal molsidomine treatment were more pronounced in female than in male FHH rats.. To evaluate whether such protective effects could also be achieved with micronutrients, and whether the gender-dependent differences could be confirmed, we tested perinatal exposure to the micronutrients L-arginine, taurine, vitamin C, and vitamin E (ATCE) in FHH rats. Perinatal micronutrients increased urinary NO metabolite, sodium and potassium excretion only at 4 weeks of age, i.e., at the end of treatment.. From 12 weeks onwards, control males had a significantly higher systolic BP (SBP) than females (P < 0.01); however after perinatal micronutrients, this difference was no longer present, indicating a pronounced antihypertensive effect of perinatal micronutrients in males (interaction P < 0.001). Development of proteinuria was attenuated by perinatal micronutrients in males and females. However, only females showed reduced glomerular filtration rate, filtration fraction, and glomerulosclerosis (GS) after perinatal micronutrients.. In sum, perinatal micronutrients that enhance NO availability ameliorated development of hypertension and proteinuria in FHH rats. Antihypertensive effects were more pronounced in male FHH offspring, whereas renal protective effects were more pronounced in female FHH offspring. Mechanisms underlying gender-specific consequences of perinatal micronutrients require further study.

Topics: Animals; Arginine; Ascorbic Acid; Blood Pressure; Dietary Supplements; Female; Hypertension; Kidney Diseases; Male; Micronutrients; Molsidomine; Nitric Acid; Nitric Oxide Donors; Potassium; Proteinuria; Rats; Rats, Inbred Strains; Sex Factors; Sodium; Taurine; Vitamin E

Oxalic acid is thought to be a significant uremic toxin that participates in the pathogenesis of uremic syndrome. AIM OF THE STUDY was to summarise results which we obtained during the study ofoxalic acid in biological fluids (plasma, saliva, urine and dialysate) in patients suffering from chronic kidney diseases (CKD), stage 3-5 and after renal transplantation.. In the retrospective study were investigated 28 healthy subjects, 112 CKD stage 1-4 patients, 39 haemodialysis patients and 27 CAPD patients. Besides 21 patients were investigated after renal transplantation. We used the following therapeutic methods: maximal water diuresis, diet with low (2g/day) and high (15g/day) sodium chloride intake, administration intravenous furosemide (20mg) and renal replacement therapy [CAPD, haemodialysis (HD), haemofiltration (HF) and postdilution haemodiafiltration (HDF)] and renal transplantation. Oxalic acid was determined by spectrophotometric method using oxalate oxidase which is free from vitamin C interference. Vitamin C was determined by spectrophotometric method.. In CKD patients and those after renal transplantation direct relationships between plasma oxalic acid and serum creatinine were found (r = 0.904 and 0.943, respectively, P < 0.001). Despite of high plasma oxalic acid in uremic patients (23.1 +/- 10 micromol/l), there was no significant difference in salivary oxalic acid between control subjects (126.5 +/- 18 micromol/l) and CKD stage 3-4 patients (133.9 +/- 23.7 micromol/I). The urinary excretion of oxalic acid during maximal water diuresis in healthy subjects (n = 15) (from 37.5 +/- 17.4 to 110.2 +/- 49.3 micromol/4 hours) and after intravenous furosemide (CKD stage 3-4, n = 15) (from 34.5 +/- 5.5 to 66.7 +/- 8.1 micromol/3 hours) increased significantly, but was not affected by high intake of NaCI in diet (CKD stage 3-4, n = 12). One tablet of Sorbifer Durules containing 100 mg Fe2+ and 60 mg vitamin C did not lead to further increase of uremic hyperoxalemia in haemodialysis patients. Four-hour HD, H F and HDF led to the significant decrease of plasma oxalic acid, but the most significant decrease was observed during HDF (63.3%).. The results of this study indicate, that renal replacement therapy is not effective for permanent reduction of elevated plasma levels of oxalic acid--important uremic toxin.

Topics: Adult; Ascorbic Acid; Chronic Disease; Creatinine; Diuresis; Female; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Oxalic Acid; Renal Dialysis; Sodium Chloride, Dietary; Toxins, Biological; Uremia

In this study, the antioxidant effect of aminoguanidine on nephrotoxicity of a single dose of cisplatin is investigated and compared with the effects of well-known antioxidants vitamin C and E combination. Tubular damage and perivascular inflammation were observed in kidney samples of the cisplatin-administered groups. Aminoguanidine and vitamin C-E combination are found to be capable of preventing these effects of cisplatin. Liver tissues of all groups were intact. Cisplatin-induced oxidative stress was evidenced by significant decrease in glutathione and significant increase in malondialdehyde levels in kidney samples. Antioxidants with cisplatin decreased malondialdehyde levels. Antioxidants with cisplatin prevented the decrease in liver glutathione levels. The nephrotoxicity was confirmed biochemically by significant elevation of serum urea and creatinine levels. Both vitamin C-E combination and aminoguanidine prevented the increase in serum urea levels according to the cisplatin group.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Chromatography, High Pressure Liquid; Cisplatin; Enzyme Inhibitors; Glutathione; Guanidines; Kidney Diseases; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Urea; Vitamin E

We assessed whether co-supplementation of vitamins C and E has additive beneficial effects on reducing the kidney damage and attenuation of the arterial pressure elevation compared to administration of either vitamin C or vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension.. Forty rats were divided into 4 study groups and 1 sham-operated group. Unilateral nephrectomy was carried out in the study groups and hypertension was induced by deoxycorticosterone injection and 1% sodium chloride and 0.2% potassium chloride added to the drinking water. Vitamins C and E (200 mg/kg/day) or combination of them were administered with DOCA-salt for 4 weeks in 3 study groups. The effects of DOCA and salt and treatment with vitamins were compared in terms of blood pressure, urinary protein excretion, antioxidant activity of the kidneys, and renal histological changes.. Four weeks of supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats had comparable significant effects in decreasing systolic blood pressure. Urinary protein excretion and histological damage did not significantly change with the combination therapy of vitamins C and E compared to the vitamin C or E alone. The renal levels of glutathione and ferric reducing/antioxidant power in combination therapy group were similar to the two other treatment groups and were significantly higher than non-treated group.. Co-administration of vitamin C and E does not have an additive beneficial effect on reducing the kidney damage and hypertension compared to either vitamin C or E alone in DOCA-salt-induced hypertension.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium Chloride; Desoxycorticosterone; Dietary Supplements; Disease Models, Animal; Drug Therapy, Combination; Hypertension; Kidney Diseases; Male; Potassium Chloride; Rats; Rats, Sprague-Dawley; Vitamin E

The present study has been carried out to investigate the role of taurine (2-aminoethanesulfonic acid), a conditionally essential amino acid, in ameliorating cadmium-induced renal dysfunctions in mice. Cadmium chloride (CdCl(2)) has been selected as the source of cadmium. Intraperitoneal administration of CdCl(2 )(at a dose of 4 mg/kg body weight for 3 days) caused significant accumulation of cadmium in renal tissues and lessened kidney weight to body weight ratio. Cadmium administration reduced intracellular ferric reducing/antioxidant power (FRAP) of renal tissues. Levels of serum marker enzymes related to renal damage, creatinine and urea nitrogen (UN) have been elevated due to cadmium toxicity. Cadmium exposure diminished the activities of enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PD) as well as non-enzymatic antioxidant, reduced glutathione (GSH) and total thiols. On the other hand, the levels of oxidized glutathione (GSSG), lipid peroxidation, protein carbonylation, DNA fragmentation, concentration of superoxide radicals and activities of cytochrome P450 enzymes (CYP P450s) have been found to increase due to cadmium intoxication. Treatment with taurine (at a dose of 100 mg/kg body weight for 5 days) before cadmium intoxication prevented the toxin-induced oxidative impairments in renal tissues. The beneficial role of taurine against cadmium-induced renal damage was supported from histological examination of renal segments. Vitamin C, a well-established antioxidant was used as the positive control in the study. Experimental evidence suggests that both taurine and vitamin C provide antioxidant defense against cadmium-induced renal oxidative injury. Combining all, results suggest that taurine protects murine kidneys against cadmium-induced oxidative impairments, probably via its antioxidative property.

Topics: Animals; Antioxidants; Ascorbic Acid; Cadmium Chloride; DNA Fragmentation; Kidney; Kidney Diseases; Male; Mice; Oxidation-Reduction; Oxidative Stress; Taurine

Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals.. Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or alpha-tocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue.. Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation.. These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cisplatin; Creatine; Drug Interactions; Glucosides; Injections, Intraperitoneal; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Mice; Oxidative Stress; Tocopherols; Urea

The aim of this study was to determine whether vitamin C, vitamin E, and selenium have protective effects against cadmium-induced renal toxicity of rats. Vitamin C (250 mg/kg/day), vitamin E (250 mg/kg/day), and sodium selenate (0.25 mg/kg/day) were given to rats orally for 8 days. Cadmium (2 mg/kg/day CdCl2) was given to rats intraperitoneally. Vitamin C, vitamin E, and selenium (in the same dose and time) were given 1 h prior to the administration of cadmium every day. The tissue and blood samples were taken from the rats for histological evaluation and biochemical analyses on the Day 9. Lipid peroxidation (LPO) and glutathione (GSH) determination were made in kidney tissue. In addition, urea and creatinine levels were determined in serum. The damage to the kidney tissue was moderate in the rats given cadmium. In this group, the distinctive changes in the proximal tubules were observed. Degenerative changes in kidney tissue were also observed in rats given vitamin C, vitamin E, selenium, and cadmium. LPO levels significantly increased and GSH levels decreased in kidney tissues following cadmium administration. Serum urea and creatinine levels were also increased in rats given cadmium. The administration of vitamin C, vitamin E, and selenium caused a significant decrease in LPO levels and an increase in GSH levels in the kidney of rats given cadmium. Serum urea and creatinine levels were decreased in rats given both the antioxidant and cadmium. It is concluded that vitamin C, vitamin E, and selenium showed some protective effect on the rat kidney.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Cadmium Chloride; Creatinine; Cytoprotection; Disease Models, Animal; Glutathione; Kidney; Kidney Diseases; Lipid Peroxidation; Male; Rats; Rats, Sprague-Dawley; Selenic Acid; Selenium Compounds; Urea; Vitamin E

Oxalic acid (OA) is thought to be a uremic toxin that participates in the pathogenesis of uremic syndrome. The objectives of this study were to: (1) evaluate the plasma levels of OA in patients with chronic renal disease with various levels of glomerular filtration rate and after renal transplantation; (2) investigate the salivary secretion of OA and ascorbic acid in healthy subjects and in patients with chronic renal failure (CRF); (3) examine the influence of water and sodium diuresis and furosemide administration on the urinary excretion of OA and ascorbic acid in healthy subjects and in CRF patients without dialysis treatment; and (4) evaluate the influence of renal replacement therapy (RRT) on secondary hyperoxalemia in hemodialysis patients.. This study was conducted at the Nephrological Department of P.J. Safárik University. Sixty-one patients with chronic renal disease, 64 CRF patients, 32 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 hemodialysis patients, 21 patients after renal transplantation, and 15 healthy subjects were examined. Maximal water diuresis, diets with low (2 g/day) and high (15 g/day) sodium intake, administration of intravenous furosemide (20 mg), and renal replacement therapy (CAPD, hemodialysis, hemofiltration, and postdilution hemodiafiltration) were utilized in the study.. In patients with chronic renal disease and those after renal transplantation, direct relationships between plasma OA and serum creatinine were found (r = 0.904 and 0.9431, respectively, P < .01). Despite a high level of plasma OA in uremic patients (23.1 +/- 10 micromol/L), there was no significant difference in salivary OA between control subjects (128 +/- 19 micromol/L) and CRF patients (135 +/- 24 micromol/L). The urinary excretion of OA during maximal water diuresis (from 37.5 to 110.3 micromol/4 hours) and after intravenous furosemide (from 34.5 to 66.7 micromol/3 hours) increased significantly, but was not affected by high intake of NaCl. The most significant decrease of plasma OA was observed during postdilution hemodiafiltration (63.3%).. Our study indicates that renal replacement therapy is not effective for a permanent reduction of elevated plasma levels of OA.

Topics: Adult; Ascorbic Acid; Atherosclerosis; Creatinine; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Uremia; Vitamin B 6

The present study was performed to investigate whether the chronic administration of antioxidant vitamin C provided morphological protection on cisplatin-induced renal damage. Wistar albino male rats were divided into control and two experiment groups, each consisting of six rats. Cisplatin (5 mg/kg/month) was administered intravenously to the second and third group for three months. After the first application of cisplatin, vitamin C (8 mg/kg/day) to the third group was administered intramuscular for 3 months. At the end of the third month, the kidney specimens of the all groups were obtained. All of these kidney specimens were processed for light and electron microscopical examination. In the second group, most of the renal corpuscle lost their normal appearance and size, especially in the corticomedullary region. The most obvious changes were encountered in the proximal tubules. These changes were tubular dilation, thickening of basement membrane, loss of brush border, vacuolization, and swollenness of mitochondria in the proximal tubule epithelial cells. In addition, infiltration foci were observed mainly in the cortical region. In the third group, which was administered cisplatin plus vitamin C, although the structural damages and morphometric changes were lessened, mononuclear cell infiltration was still observed. This study suggests that the chronic administration of vitamin C may be of therapeutic benefit on cisplatin nephrotoxicity.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cisplatin; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubules, Distal; Male; Rats; Rats, Wistar

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In the present study, the effect of long-term Sch B treatment (1-10 mg/kg/d x 15) on gentamicin-induced nephrotoxicity was examined in rats. Sch B treatment protected against gentamicin-induced nephrotoxicity, as evidenced by significant decreases in plasma creatinine and blood urea nitrogen levels. The nephroprotection was associated with the enhancement in renal mitochondrial antioxidant status, as assessed by the level/activity of reduced glutathione, alpha-tocopherol and Mn-superoxide dismutase, as well as the improvement/preservation of mitochondrial functional and structural integrity, as assessed by the extents of ATP generation capacity, malondialdehyde production, Ca2+ loading and cytochrome c release, as well as the sensitivity to Ca2+-induced permeability transition, in control and gentamicin-intoxicated rats. In conclusion, long-term Sch B treatment could enhance renal mitochondrial antioxidant status as well as improve mitochondrial functional and structural integrity, thereby protecting against gentamicin nephrotoxicity.

Topics: Adenosine Triphosphate; Animals; Antibiotics, Antineoplastic; Antioxidants; Ascorbic Acid; Cyclooctanes; Female; Gentamicins; Glutathione; Kidney; Kidney Diseases; Lignans; Mitochondria; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

To study the effects of BSO, GSH, Vit-C and DMPS on the nephrotoxicity of mercury.. The rats in groups 1, 2 and 3 were sc injected with 0.75, 1.5 and 2.5 mg/kg HgCl2, respectively. Fourth group rats were ip injected with 0.5 mmol/kg BSO and 4h later sc administrated with 0.75 mg/kg HgCl2. The rats in groups 5, 6 and 7 were ip injected with 3 mmol/kg GSH, 4 mmol/kg Vit-C, 200 micromol/kg DMPS, respectively, and 2 h later sc administrated with 2.5 mg/kg HgCl2. Eighth group rats were sc injected with saline as a control. Mercury concentrations in the liver, renal cortex and urine, urinary NAG, ALP, LDH activities, protein and BUN contents were determined.. Urinary NAG, ALP activities, protein and BUN contents in the rats of BSO pretreatment group were significantly higher than that of 0.75 mg/kg HgCl2 alone group and control group. As compared with 2.5 mg/kg HgCl2 alone group, urinary NAG, ALP, LDH activities, urinary protein and BUN contents decreased significantly.. BSO pretreatment could enhance the renal toxicity of mercury and GSH, Vit-C and DMPS pretreatment had antagonistic effects on nephrotoxicity of mercury.

Topics: Animals; Antioxidants; Ascorbic Acid; Buthionine Sulfoximine; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Female; Glutathione; Kidney Cortex; Kidney Diseases; Liver; Male; Mercuric Chloride; Mercury Poisoning; Rats; Rats, Wistar; Unithiol

This study was carried out to investigate smoke-induced structural and biochemical changes and protective effects of co-administered melatonin and vitamin C in the kidney. Twenty-four Wistar adult female rats were used in this study. Animals were divided into four groups. The first group rats were used as control. The second group of rats inhaled cigarette smoke. Smile smoke inhaling third and fourth group rats received melatonin and vitamin C, respectively. At the end of experimental study, kidney tissues and blood samples were taken under ether anesthesia. Tissues were prepared and examined by light microscopy. Malondialdehyde and glutathione levels and catalase activity were determined. By light microscopic observation, a decrease of Bowman space of some renal corpuscles, foamy-like tubules, dilatation and congestion of the peritubuler vessels, and atrophy of the some renal corpuscles were observed in group II. In groups III and IV melatonin and vitamin C relatively protected the kidney tissue against smoke intoxication. Biochemical examination showed that malondialdehyde and glutathione levels and catalase activity in group II were higher than in group I. Melatonin and vitamin C injection to group III and IV caused a decrease in malondialdehyde and glutathione levels. Catalase activity did not change in these groups. We have shown that cigarette smoke inhalation caused structural changes in the kidney. However, melatonin and vitamin C administration produced in some degree protection against smoke-induced damage.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Female; Glutathione; Kidney Diseases; Malondialdehyde; Melatonin; Rats; Rats, Wistar; Tobacco Smoke Pollution

Oxidative stress, resulting from an imbalance between prooxidant and antioxidant systems in favor of the former, largely contributes to immune system deregulation and complications observed in end-stage renal disease (ESRD) and patients treated with hemodialysis. Reactive oxygen species and free radicals are involved in the nephrotoxicity induced by a synthetic anticancer drug cisplatin.. A comparative study on the nephroprotective effects of antioxidant vitamins (250 and 500 mg/kg, p.o.), vitamin C (ascorbic acid) and vitamin E (alpha-tocopherol), was evaluated using cisplatin (10 mg/kg body wt, i.p.) induced oxidative renal damage in mice. Urea and creatinine in serum were estimated for the renal function. Antioxidant status was estimated in kidney homogenate.. We found that both vitamins at 500 mg/kg significantly (P<0.01) protected the nephrotoxicity induced by cisplatin. The cisplatin induced increase of urea and creatinine concentrations were reduced in the vitamins plus cisplatin (250 and 500 mg/kg, p.o.)-treated groups. However the cisplatin induced decline of renal antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities were increased only in the 500 mg/kg vitamins treated groups. Both vitamins at 250 and 500 mg/kg could increase the concentration of reduced glutathione (GSH) and protected the increase of cisplatin induced lipid peroxidation.. Higher doses of vitamins are effective to protect oxidative renal damage and vitamin C is the better nephroprotective agent than vitamin E. The protection is mediated partially by preventing the decline of renal antioxidant status.

Topics: alpha-Tocopherol; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Catalase; Cisplatin; Creatinine; Glutathione; Glutathione Peroxidase; Kidney Diseases; Male; Malondialdehyde; Mice; Superoxide Dismutase; Urea; Vitamins

Despite recent discoveries of molecules in podocytes, the mechanisms behind most conditions of proteinuria are still poorly understood. To understand more about this delicate barrier, we studied the functional and morphological effects of mild (15 min) renal ischemia-reperfusion injury (IRI). Renal function was studied in rats in vivo, followed by a more detailed analysis of the glomerular barrier in cooled (8 degrees C) isolated perfused kidneys (cIPK). Renal blood flow was quickly restored, whereas the glomerular filtration rate remained halved 30 min after IRI. Tubular cell activity was intact as judged from the unaffected Cr-EDTA U/P concentration ratio. In vivo, the fractional clearance (theta) for albumin increased 16 times. In rats subjected to cIPK starting 30 min after in vivo IRI, theta(albumin) was 15 times and theta(Ficoll_36angstroms) 1.8 times higher than in control cIPKs. According to the heterogeneous charged fiber model, IRI reduced the fiber charge density to 38% of control (P < 0.01, n = 7). Morphometric analysis with electron microscopy did not reveal any changes in the podocytes or the glomerular basement membrane (GBM) after IRI, suggesting more subtle changes of the GBM and/or the endothelial glycocalyx. We conclude that mild renal IRI induces formation of reactive oxygen species, massive proteinuria, and loss of charged fibers with no apparent change in morphology. These novel findings stress the importance of other components of the barrier, such as proteoglycans produced by the glomerular cells, and provide a tentative explanation for the mechanisms behind proteinuria in glomerulonephritis, for example.

Topics: Albumins; Animals; Ascorbic Acid; Blood Pressure; Capillary Permeability; Edetic Acid; Female; Glomerular Filtration Rate; Kidney Diseases; Kidney Glomerulus; Membranes, Artificial; Microscopy, Electron; Oxidative Stress; Proteoglycans; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Serum Albumin, Radio-Iodinated

Abdominal aortic surgery can cause ischemic/reperfusion (I/R) injury in not only the lower extremities, but also in the remote organs and tissues such as lungs, kidneys, heart, and liver during abdominal aortic surgery. It can result in mortality and morbidity because of the remote organ injury in early postoperative period. In this study, we investigate the effects of iloprost and vitamin C on the kidney remote organ damage after I/R following abdominal aortic surgery.. Thirty-four adult male Wistar rats were used and divided into five groups. I/R was studied infrarenally in the abdominal aorta following a median laparotomy. The left kidney was excised immediately following the laparotomy in group I (n = 6, normal group). Group II (n = 6) was the sham group. Group III (n = 6, control group) was subjected to 3 h of ischemia followed by an hour of reperfusion. Group IV (n = 8) was given iloprost 20 ng/kg/min during I/R period before aortic-clamping. Group V (n = 8) was given vitamin C 100 mg/kg during I/R period before aortic-clamping. Arterial blood samples were obtained to determine the levels of blood pH, pO(2) (mmHg), pCO2 (mmHg), HCO(3) (mmol/L), and plasma malondialdehyde (MDA, nmol/mL) at the end of reperfusion period in all groups. The left kidneys were used for remote measurements of tissue MDA (nmol/g.w.t) and scored by histopathological examination for acute inflammation.. While the arterial blood pO(2) and HCO(3) levels significantly increased, the plasma and renal parenchymal MDA levels significantly decreased in both group IV and group V when compared to group III (P < 0.05). Histopathological and acute inflammation scores statistically decreased in both group IV and V compared with group III (P < 0.05). Although MDA levels, histopathologic and acute inflammation scores in group V were lower than group IV, the differences were not statistically significant (P > 0.05).. Both iloprost and vitamin C decreased remote organ damage on the kidney after I/R of lower extremities in the rat model. However, vitamin C is more effective than iloprost in preventing postoperative renal dysfunction.

Topics: Animals; Antioxidants; Aorta, Abdominal; Ascorbic Acid; Atrophy; Carbon Dioxide; Hindlimb; Iloprost; Kidney; Kidney Diseases; Male; Malondialdehyde; Oxygen; Rats; Rats, Wistar; Reperfusion Injury; Vasodilator Agents

The objective of this study was to compare the beneficial effects of caffeic acid phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin-induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i) control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route; (iii) vancomycin plus CAPE-vancomycin with 10 micromol/kg CAPE; (iv) vancomycin plus vitamin C-vancomycin (intraperitoneally) with 200 mg/dl vitamin C in drinking water; (v) vancomycin plus vitamin E-vancomycin with 1000 mg/kg body weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine-vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine. Vancomycin treatments were started 1 day after the first administrations of these agents and continued for 7 days. At the end of the experiments, catalase activity was significantly decreased by vancomycin in kidney homogenates (P < 0.05). Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the blood urea nitrogen levels increased by vancomycin, although significant differences were detected only in the vitamins E and C groups (P < 0.05). Increased renal malondialdehyde and nitric oxide levels by vancomycin were significantly suppressed by agents used in the study (P < 0.05). Histopathological examination demonstrated prominent damages in the vancomycin-treated group. Vitamin E was the most beneficial agent on vancomycin-induced tubular damage, followed by vitamin C, N-acetylcysteine and CAPE treatments, respectively. The data suggest that vitamin E, as well as vitamin C, N-acetylcysteine and CAPE, could be useful for reducing the detrimental effects on vancomycin-induced toxicity in kidneys.

Topics: Acetylcysteine; Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Caffeic Acids; Catalase; Disease Models, Animal; Drinking; Drug Combinations; Injections, Intramuscular; Injections, Intraperitoneal; Kidney; Kidney Diseases; Male; Phenylethyl Alcohol; Rats; Rats, Wistar; Vancomycin; Vitamin E; Water Supply

Topics: Animals; Ascorbic Acid; Endotoxemia; Kidney Diseases; Rats; Statistics as Topic; Vitamin A

Renal ischemia as a course of renal transplantation is a common cause of renal dysfunction as renal failure. The purpose of this study was to investigate the influence of ascorbic acid on blood urea nitrogen (BUN), creatinine (Cr) and resistive index (RI) for dog models with renal ischemia-reperfusion (I/R) injury. Renal ischemia was induced on 6 Beagle dogs. The left kidney was exposed to normothermic ischemia for a short period at 30 min followed by reperfusion. On the blood Cr level and RI, there was no significant difference comparing both groups. 14 days after I/R injury a significant reduction on the blood BUN level was observed in the vehicle group (34.06 mg/dl) compared to that of ischemia induced treated group (10.3 mg/dl) (p < 0.05). In conclusion, administration of ascorbic acid for renal ischemic-reperfusion injury had influence on blood BUN level, but it was not revealed the influence on blood Cr and RI.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Urea Nitrogen; Creatinine; Dog Diseases; Dogs; Kidney Diseases; Male; Random Allocation; Reperfusion Injury; Ultrasonography, Doppler, Color

Contrast media-associated acute renal failure represents the third most common cause of in-hospital renal function deterioration after decreased renal perfusion and post-operative renal insufficiency. Although generally benign, this complication is associated with a mortality rate ranging from 3.8 to 64%, depending on the increase of creatinine concentration. Multiple drugs have been tested in an attempt to prevent this complication. Central to the pathophysiology of contrast-induced nephrotoxicity (CIN) is an alteration in renal hemodynamics. In an effort to reverse these hemodynamic changes, vasodilators and diuretics have been tested as prophylactic drugs. However, their effectiveness has not been confirmed. Recently, considerable interest has resulted from the initial positive data on the effectiveness of prophylactic administration of antioxidant compounds, such as acetylcysteine and ascorbic acid. In this review, we focus on the effectiveness of pharmacologic therapies for preventing CIN.

Topics: Acetylcysteine; Acute Kidney Injury; Antioxidants; Ascorbic Acid; Calcium Channel Blockers; Contrast Media; Dopamine; Humans; Kidney; Kidney Diseases; Randomized Controlled Trials as Topic; Vasoconstriction

Human erythrocytes can take up dehydroascorbate on the glucose transporter 1 (GLUT 1) and reduce it to ascorbate. Intraerythrocyte ascorbate was proved to be directly responsible for decreased oxidation of extraerythrocytic ascorbate. In addition to spontaneous and irreversible loss of ascorbate in plasma, the hemodialysis (HD) process itself consumes plasma ascorbate. However, intraerythrocyte ascorbate status in uremic patients during HD has yet to be reported.. Plasma and intraerythrocyte ascorbate, dehydroascorbate, GLUT 1 expression on erythrocyte membranes, and in vitro studies of "erythrocyte ascorbate recycling" were investigated in age- and sex-matched healthy subjects (control group) and HD patients (HD group).. Intraerythrocyte ascorbate concentrations decreased after 1 HD session compared with pre-HD and recovered to pre-HD values 2 days later, whereas plasma ascorbate concentrations did not recover. In vitro studies suggested that erythrocytes of HD patients have a stronger ability to maintain intracellular ascorbate concentrations compared with healthy subjects. This ability could be inhibited by cytochalasin B (GLUT 1 inhibitor). We also found increased GLUT 1 expression (P = 0.002) on erythrocyte membranes in the HD group compared with the control group.. Erythrocytes of uremic patients lost large amounts of ascorbate during HD, but regained it to the pre-HD level 2 days later. Enhanced GLUT 1 expression on erythrocyte membranes for HD patients may contribute to better preservation of intracellular ascorbate compared with healthy subjects.

Topics: Aged; Ascorbic Acid; Blotting, Western; Chromatography, High Pressure Liquid; Cytochalasin B; Dehydroascorbic Acid; Erythrocyte Membrane; Erythrocytes; Female; Glucose Transporter Type 1; Humans; Kidney Diseases; Male; Middle Aged; Renal Dialysis; Time Factors; Uremia

Gentamicin (GM) is an effective antibiotic against severe gram-negative infections. However it can produce nephrotoxicity in human. Reactive oxygen species (ROS) have been proposed as the causative factors of the renal side effects the drug. This study was performed to investigate the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney. Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: group 1 (Control) was perfused with Tyrode solution; group 2 (GM), 200 microg ml(-1) GM was added to the perfusate; group 3 (GM + Vit C), as group 2 with vitamin C added to the drinking water for 3 days (200 mg l(-1)) and to the perfusate (100 mg l(-1)); group 4 (GM + Vit E), as group 2 with vitamin E (100 mg (100 g body weight)(-1), i.m.) injected 12 h before the start of the experiment; group 5 (GM + Vit C + Vit E) as group 2 with vitamin E and C co-administered (concentrations and conditions as in groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N-acetyle-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) content were measured. GM caused a significant nephrotoxicity demonstrated by an increase in urinary LDH, NAG and ALP activities. Reduction in GSH content and a marked decrease in GFR were observed compared to controls. Vitamin C inhibited the GM-induced increase in urinary enzyme activities but did not show a significant effect on the GSH content or GFR. Vitamin E prevented the GM-induced reduction in GSH level without a significant improvement in GFR. Co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity demonstrating by preservation of GFR and GSH levels and prevention of increase in urinary enzyme activities. We conclude that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation in GM-induced nephrotoxicity.

Topics: Acetylglucosamine; Acetylglucosaminidase; Alkaline Phosphatase; Animals; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Gentamicins; Glomerular Filtration Rate; Glutathione; Histocytochemistry; In Vitro Techniques; Inulin; Kidney Diseases; L-Lactate Dehydrogenase; Male; Rats; Rats, Sprague-Dawley; Vitamin E

There is no specific treatment for paracetamol-induced renal damage. Vitamin C is an outstanding chain-breaking antioxidant and a free radical scavenger. The present study was undertaken to determine whether large doses of vitamin C are useful in the treatment of paracetamol-induced renal damage.. Renal injury was induced in rats by the administration of 1 g/kg body weight paracetamol intraperitoneally. Some rats received intraperitoneal injections of vitamin C (250, 500, or 1000 mg/kg body wt) at 1.5 h, 6 h, 9 h, or 16 h after the administration of paracetamol, and the rats were killed 24 h after the administration of paracetamol.. Renal injury was accompanied by a decrease in nonprotein thiol and protein thiol in the kidneys of paracetamol-treated rats. The administration of vitamin C to the paracetamol-treated rats prevented renal damage either completely or partially. Lower doses of vitamin C were beneficial in the prevention of paracetamol-induced renal injury when administered early and higher doses were beneficial when administered later. In the paracetamol-treated rats that responded to vitamin C, renal nonprotein thiol level and protein thiol were restored almost completely. Interestingly, a highly significant inverse correlation was obtained between renal nonprotein thiol level and plasma creatinine.. Megadoses of vitamin C may be beneficial in the treatment of paracetamol-induced renal damage. The mechanism of protection by vitamin C appears to be the regeneration of nonprotein thiol.

Topics: Acetaminophen; Animals; Antioxidants; Ascorbic Acid; Creatinine; Dose-Response Relationship, Drug; Free Radical Scavengers; Kidney; Kidney Diseases; Male; Rats; Rats, Wistar; Sulfhydryl Compounds; Survival Rate

The goal of this study was to test the hypothesis that oxidative stress in Dahl salt-sensitive (SS) rats on a high-sodium intake contributes to the progression of renal damage, the decreases in renal hemodynamics, and the development of hypertension. We specifically studied whether antioxidant therapy, using vitamins C and E, could help prevent renal damage and glomerular filtration rate (GFR) and renal plasma flow reductions and attenuate the increases in arterial pressure. Thirty-three 7- to 8-week old Dahl SS/Rapp strain rats were placed on either a high-sodium (8%) or a low-sodium (0.3%) diet with or without vitamin E (111 IU/d) in the food and 98 mg/d vitamin C in the drinking water for 5 weeks. Rats were equipped with indwelling arterial and venous catheters at day 21. By day 35 in the rats with high-sodium diet, vitamin C and E treatment significantly decreased renal cortical and medullary O2*- release, mean arterial pressure, urinary protein excretion, glomerular necrosis, and renal tubulointerstitial damage. At this time, GFR significantly decreased in the high-sodium diet group (1.6+/-0.2 mL/min) when compared with either the high-sodium plus vitamins C and E (2.9+/-0.2 mL/min) or the low-sodium diet group (2.9+/-0.3 mL/min). In SS rats on high-sodium diet, renal plasma flow decreased 40%, and this reduced flow was restored by vitamin treatment. In Dahl salt-sensitive hypertension, increased oxidative stress plays an important role in the renal damage, decreases in renal hemodynamics, and increases in arterial pressure that occur. Antioxidant treatment with vitamins C and E improves renal dysfunction, lessens renal injury, and decreases arterial pressure in Dahl salt-sensitive hypertension.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Heart Rate; Hemodynamics; Hypertension; Kidney; Kidney Cortex; Kidney Diseases; Kidney Medulla; Male; Proteinuria; Rats; Rats, Inbred Dahl; Renal Circulation; Sodium Chloride; Superoxides; Vitamin E

The monitoring of uric acid (UA) and p-aminohippuric acid (PAH) levels in biological samples is routinely carried out in clinical laboratories as an indication of renal disease. With the aim of investigation of the correlation between the trace amounts of UA and PAH in human saliva or urine and renal diseases, we carried out the determination of UA and PAH in human saliva and urine by using capillary electrophoresis with electrochemical detection (CE-ED) in this work. Under the optimum conditions, UA, PAH and three coexisting analytes could be well separated within 21 min at the separation voltage of 14 kV in 80 mmol/L borax running buffer (pH 9.2). Good linear relationship was established between peak current and concentration of analytes over two orders of magnitude with detection limits (S/N = 3) ranged from 5.01 x 10(-7) to 2.00 x 10(-6) mol/L for all analytes. The result shows that this proposed method could be successfully applied for the study on the correlation between the levels of UA and PAH in human saliva and urine and renal diseases, and provide an alternative and convenient method for the fast diagnosis of renal disease.

Topics: Ascorbic Acid; Electrochemistry; Electrophoresis, Capillary; Humans; Hydrogen-Ion Concentration; Hypoxanthine; Kidney Diseases; p-Aminohippuric Acid; Reproducibility of Results; Saliva; Sensitivity and Specificity; Uric Acid; Xanthine

To study the renal toxicity caused by mercury administrated once and to observe the effects of buthionine sulfoximine (BSO), gluthionein (GSH), vitamin C (VC), and sodium 2,3-dimercato-1-propanesulfonate (DMPS) pretreatment on the nephrotoxicity of mercury.. Sixty-four Wistar rats were divided randomly into eight groups, i. e., control group, low, middle and high dose mercury groups and BSO, GSH, VC, DMPS pretreatment groups. The low, middle, and high dose mercury group rats were subcutaneously (sc) injected with 0.75, 1.5, and 2.5 mg/kg HgCl2, respectively. The BSO pretreatment group rats were intraperitoneally (ip) injected with 0.5 mmol/kg BSO and four hours later sc administrated with 0.75mg/kg HgCl2. The GSH, VC and DMPS pretreatment group rats were ip injected with 3 mmol/kg GSH, 4mmol/kg VC, 200 micromol/kg DMPS, respectively, and two hours later sc administrated with 2.5 mg/kg HgCl2. The control group rats were sc injected with saline at corresponding time. The volume of injection was 5 ml/kg body weight. The 12 h urine samples were collected after 12 hours. After 48 hours, the blood samples were collected and then centrifuged to get the serum. The liver and renal cortex were also removed. Mercury contents in the liver, renal cortex, and urine samples were measured. Urinary NAG, ALP, LDH activities, urinary protein and BUN contents were also determined.. Mercury concentrations in the liver, renal cortex, and urine samples increased with mercury dose increasing. Mercury contents in the renal cortex presented evident dose-effect relationship. Mercury concentrations in the liver of high-dose mercury group were higher significantly than that of low, middle-dose mercury group, and control group. The concentrations of urinary mercury in the middle and high dose mercury groups were higher significantly than that of control group. Compared with 0.75mg/kg HgCl2 alone group, BSO pretreatment increased mercury concentrations in the liver, but decreased the concentrations in the renal cortex and urine. Mercury concentrations in the liver of GSH, VC and DMPS pretreatment groups were lower than that of 2.5 mg/kg HgCl2 alone group. Urinary NAG, ALP, LDH activities, urinary protein and BUN contents increased with mercury dose increasing, and the values in the animals of 2.5 mg/kg HgCl2 mercury group were higher significantly than that of control, 0.75 and 1.5 mg/kg HgCl2 groups. Urinary NAG, ALP activities, urinary protein and BUN contents in the rats of BSO pretreatment were higher than that of 0.75 mg/kg HgCl2 alone group and control group. Compared with 2.5 mg/kg HgCl2 alone group, urinary NAG, ALP, LDH activities, urinary protein and BUN contents decreased significantly.. Mercury concentrations in the liver, renal cortex, and urine of the rats increased with mercury dose increasing. BSO pretreatment could enhance the renal toxicity induced by mercury, however, GSH, VC, and DMPS pretreatment had antagonistic effects on nephrotoxicity of the mercury.

Topics: Animals; Antioxidants; Ascorbic Acid; Buthionine Sulfoximine; Dose-Response Relationship, Drug; Female; Glutathione; Kidney Cortex; Kidney Diseases; Male; Mercuric Chloride; Mercury Poisoning; Random Allocation; Rats; Rats, Wistar; Unithiol

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Antioxidants; Ascorbic Acid; Drug Interactions; Kidney Diseases; Male; Rats; Rats, Wistar

Positron emission tomography is increasingly used for the diagnosis of occult infection or malignancy. The altered metabolic rate of cells in areas of malignancy or infection provides a sensitive method to identify pathology that is otherwise not identified by standard imaging methods. This case report describes a patient who presented with a pyrexia of unknown origin and renal impairment. She had a positron emission tomography scan that showed intense accumulation of fluoro-deoxy-glucose in both kidneys. Subsequent renal biopsy results showed a diagnosis of malacoplakia, the treatment of which resulted in a resolution of the fever and a stabilization of renal function. This is the first report of the positron emission tomographic appearance of renal malacoplakia.

Topics: Abdominal Pain; Ascorbic Acid; Female; Fever of Unknown Origin; Fluorodeoxyglucose F18; Gastrointestinal Diseases; Hematuria; Humans; Kidney Diseases; Malacoplakia; Middle Aged; Radiopharmaceuticals; Tomography, Emission-Computed; Trimethoprim

To investigate whether combined pretreatment with lipid- and water-soluble antioxidants gave better restoration of energy phosphates after ischaemia-reperfusion of rabbit kidneys than single pretreatment with a lipid-soluble antioxidant.. Thirteen New Zealand white rabbits were used for the study. Changes in energy phosphates were measured in vivo using volume-selective 31P magnetic resonance spectroscopy. The indeno-indole compound H290/51 was chosen as a lipid-soluble antioxidant and ascorbate as a water-soluble antioxidant.. The combined pretreatment led to significantly better restoration of the beta-adenosine triphosphate:inorganic phosphate ratio after 60 min of ischaemia and 120 min of reperfusion compared with the single pretreatment. Analyses of blood pressure and blood gas changes showed that the beneficial effect of combined pretreatment was not caused by a better general condition of the animals in that group but by a direct effect on the kidneys.. Combined pretreatment with lipid- and water-soluble antioxidants leads to better restoration of energy phosphates in rabbit kidneys subjected to ischaemia-reperfusion compared with single pretreatment with a lipid-soluble antioxidant.

Topics: Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Disease Models, Animal; Female; Indoles; Ischemia; Kidney Diseases; Kidney Function Tests; Lipid Peroxidation; Magnetic Resonance Spectroscopy; Male; Monitoring, Physiologic; Phosphorus Isotopes; Probability; Rabbits; Random Allocation; Reperfusion Injury; Sensitivity and Specificity; Solubility

Topics: Anemia, Iron-Deficiency; Ascorbic Acid; Bacteremia; Chronic Disease; Drug Hypersensitivity; Erythropoietin; Ferritins; Humans; Injections, Intravenous; Iron; Kidney Diseases; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis

3,4-Dichlorophenylhydroxylamine (3,4-CPHA) is the N-hydroxyl metabolite of 3,4-dichloroaniline. 3,4-Dichloroaniline is a breakdown product of the herbicide Propanil. Previous work has shown that 3,4-dichloroaniline is acutely toxic to the kidney and bladder. The purpose of this study was to examine the in vitro toxicity of 3,4-dichlorophenylhydroxylamine. Renal cortical slices were prepared from male Fischer 344 rats (190-250 g) and were incubated with 0-0.5 mM 3,4-CPHA for 30-120 min under oxygen and constant shaking. 3,4-CPHA produced a concentration and time dependent alteration in lactate dehydrogenase (LDH) leakage, organic ion accumulation and pyruvate stimulated gluconeogenesis. Glutathione levels were diminished within 60 min below control values by 0.1 and 0.5 mM 3,4-CPHA. A 30 min pretreatment with 0.1 mM deferoxamine did not alter 3,4-CPHA toxicity. Alterations in pyruvate stimulated gluconeogenesis and LDH leakage were comparable between vehicle and deferoxamine pretreated tissues. Other studies examined the effect of (1 mM) glutathione, 2 mM ascorbic acid and 1 mM dithiothreitol (DTT) on toxicity. Pretreatment for 30 min with vehicle or 1 mM DTT induced comparable changes in LDH leakage and pyruvate stimulated gluconeogenesis. Pretreatment for 30 min with 1 mM glutathione or 2 mM ascorbic acid reduced 3,4-CPHA toxicity. LDH leakage was not elevated as markedly in renal slices pretreated with glutathione relative to slices pretreated with vehicle. These results indicate that 3,4-CPHA toxicity is through an iron independent mechanism. 3,4-CPHA cytotoxicity was reduced by pretreatment with glutathione or ascorbic acid suggesting formation of a reactive intermediate.

Topics: Analysis of Variance; Aniline Compounds; Animals; Ascorbic Acid; Deferoxamine; Dithiothreitol; Dose-Response Relationship, Drug; Gluconeogenesis; Glutathione; Hydroxylamines; In Vitro Techniques; Kidney Cortex; Kidney Diseases; L-Lactate Dehydrogenase; Male; Pyruvic Acid; Rats; Rats, Inbred F344

This study was designed to assess the parameters of myocardial oxidative stress and related cardiac morphological changes following intraperitoneal cocaine exposure in rats. The cardiac levels of reduced glutathione(GSH), oxidised glutathione(GSSG), ascorbic acid (AA), and the production of malondialdehyde (MDA) were measured, as well as the variations of activity in the enzyme systems involved in cell antioxidant defence, glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). After chronic cocaine administration for 30 days GSH was significantly depleted in the heart from 30 min (P < 0.001) to 24 h (P < 0.001) after exposure, and GSSG was increased for a similar time (P < 0.05 at 30 min and P < 0.01 at 24 h). SOD increased during the first hour (P < 0.001), GR and GSH-Px both increased from 30 min to 24 h, and these increases were statistically significant (P < 0.01 and P < 0.001 at 30 min and P < 0.01 and P < 0.001 at 24 h, respectively). The AA levels increased after 1 h (P < 0.01), remaining significantly so for 24 h (P < 0.001) and MDA increased from 30 min to 24 h, all values being highly significant (P < 0.001). The body weight was significantly (P < 0.001) reduced in both cocaine groups (40 mg/kg x 30 days and 40 mg/kg x 10 days + 60 mg/kg x 20 days). The heart weight (P < 0.01) and its percentage of the body weight (P < 0.001) were significantly higher in these two groups than in the controls. Similarly, in the noradrenaline 4 mg/ kg x 30 days group, the body weight was significantly (P < 0.001) reduced and the heart weight (P < 0.01) and its percentage of body weight (P < 0.001) were significantly higher than in the controls. In comparing the cocaine and noradrenaline experiments, the frequency and extent of cardiac lesions obtained with 40 mg/kg x 10 days + 60 mg/kg x 20 days of cocaine were similar to those with 8 mg/kg of noradrenaline at 24 h. In this experimental model, cocaine administration compromised the antioxidant defence system of the heart associated with a significant increase of heart weight and the percentage of body weight.

Topics: Animals; Apoptosis; Ascorbic Acid; Cocaine; Dopamine Uptake Inhibitors; Glutathione; Heart; Kidney Diseases; Male; Malondialdehyde; Myocardium; Oxidative Stress; Rats; Statistics, Nonparametric; Superoxide Dismutase; Vasoconstrictor Agents

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is associated with nephrotoxicity. In the present study we report the effects of different amounts of vitamin C (50, 100 or 200 mg kg(-1)body wt.) in rat kidneys treated with cisplatin (5 mg kg(-1)body wt.), using single doses of both compounds. Cisplatin administration induced lipid peroxidation which was accompanied by a decrease in renal glutathione level in animals killed 7 days after treatments. Furthermore, an increase in serum creatinine has been observed. Treatment of animals with vitamin C 10 min prior to the cisplatin inhibited cisplatin-mediated damage. Seven days after vitamin C plus cisplatin treatments, the depleted level of glutathione and changes in the creatinine clearance recovered to significant levels (P<0.05). Similarly, the enhanced serum creatinine levels which are indicative of renal injury showed a significant reduction (P<0.05) with the three doses of vitamin C tested. The protective effect of vitamin C was dose-dependent. The results suggest that vitamin C is an effective chemoprotective agent against nephrotoxicity induced by the antitumoral cisplatin in Wistar adult rats.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Glutathione; Kidney Diseases; Lipid Peroxidation; Male; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Urodynamics

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GS

Topics: Animals; Anthocyanins; Antioxidants; Apoptosis; Ascorbic Acid; beta Carotene; Biological Availability; Cardiovascular Diseases; Dose-Response Relationship, Drug; Flow Cytometry; Free Radical Scavengers; Free Radicals; Humans; Keratinocytes; Kidney Diseases; Liver Diseases; Neoplasms; Plant Extracts; Proanthocyanidins; Seeds; Vitamin E

Topics: Adult; Anastomosis, Surgical; Ascorbic Acid; Calcinosis; Combined Modality Therapy; Female; Humans; Hydrogen-Ion Concentration; Ileum; Kidney Diseases; Kidney Pelvis; Kidney Transplantation; Postoperative Complications; Pyelitis

Enzymatic antioxidant defense system and antioxidant defense potential (AOP) were studied in kidney tissue from rabbits treated with cyclosporine (CsA, 25 mg/kg/day), antioxidant vitamins (E, 100 mg/kg/day plus C, 200 mg/ kg/day), and CsA plus antioxidant vitamins, and in kidney tissue from control animals. Although no change was observed in superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) and catalase (CAT) activities were found decreased in kidney tissue exposed to CsA for 10 days compared with control tissue. The level of thiobarbituric acid-reagent substances (TBARS) was higher and antioxidant defense potential (AOP) lower in the CsA-treated group compared with the other groups. Histopathological examination reveals important subcellular damage in the renal tissue from the animals treated with CsA. Antioxidant vitamin therapy caused full improvement in the enzyme activities, TBARS levels and AOP, but the subcellular damage was partly ameliorated in the CsA plus vitamin group. Results suggest that CsA impairs the antioxidant defense system and reduces the antioxidant defense potential in the renal tissue. Antioxidant vitamin treatment protects the tissue in part against toxic effects of the drug.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Cyclosporine; Cyclosporins; Drug Therapy, Combination; Enzyme Inhibitors; Glutathione Peroxidase; Kidney; Kidney Diseases; Kidney Glomerulus; Malondialdehyde; Rabbits; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P < 0.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P < 0.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.

Topics: Animals; Ascorbic Acid; Blood Urea Nitrogen; Carcinogens; Catalase; Creatinine; Ferric Compounds; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Hydrogen Peroxide; Kidney; Kidney Diseases; Lipid Peroxidation; Microsomes; Nitrilotriacetic Acid; Ornithine Decarboxylase; Oxidative Stress; Rats; Vitamin E

The protective effect of vitamin E and C on sodium chromate (Cr) and thallium (Tl) induced nephrotoxicity was tested in 10- and 55-day-old rats. The concentrations of Cr and Tl were determined in renal cortex and medulla by atomic absorption spectrometry. Urinary volume and protein excretion as well as blood urea nitrogen (BUN) concentration were determined as parameters of nephrotoxicity. Cr and Tl induced nephrotoxicity was significantly more expressed in adult than in young rats. In Cr and Tl nephrotoxicity the protective effect of vitamin E was evident in both age groups. Vitamin E decreased Tl concentration in renal tissue. Therefore its protective effect is not to be attributed to its known antioxidant effect but to lower Tl concentration in renal tissue. Vitamin C was protective in Cr and Tl induced nephrotoxicity in adult rats without influence on metal concentrations in renal tissue. The dose necessary for protection against toxic Cr action in adult rats was not tolerated by young rats. The combined administration of both vitamins abolished the protective effect against Cr nephrotoxicity of the administration of each vitamin alone in adult rats. When vitamin E and C were administered in Tl treated adult and young rats the protective effect was the same as after the administration of each vitamin alone. Possible mechanisms are discussed.

Topics: Animals; Ascorbic Acid; Blood Urea Nitrogen; Chromates; Female; Kidney; Kidney Diseases; Male; Proteinuria; Rats; Rats, Wistar; Sodium Compounds; Spectrophotometry, Atomic; Thallium; Urination; Vitamin E

The present study is concerned with the influence of processes occurring during dialysis on the antioxidant capacity of plasma and saliva. The biological fluids were also tested for uric acid and total protein content. Before hemodialysis, plasma antioxidant status of hemodialyzed patients appears slightly higher than the corresponding status in normal subjects; after hemodialysis it is found unchanged. The result can be explained by a balance between a reduction in uric acid plasma content, due to the dialytic procedure, and an increase in protein content, possibly due to a dialysis-related hemoconcentration. Moreover, pre-dialysis total antioxidant capacity of whole saliva samples is higher than in healthy individuals and drastically decreases towards normal values following dialytic procedure. Our data indicate a certain concentration of the uric acid in the saliva of hemodialyzed patients and evidence that both total protein concentration and uric acid level show a good correlation with saliva total antioxidant capacity, suggesting that proteins are major antioxidants of this fluid. Further observations are needed to assess whether this improved saliva antioxidant ability has any consequence on the periodontal conditions of hemodialyzed subjects.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Blood Proteins; Female; Humans; Kidney Diseases; Male; Middle Aged; Proteins; Renal Dialysis; Saliva; Uric Acid

To investigate the effects of neutrophil activation during hemodialysis (HD), blood markers of oxygen free radical (OFR) activity were studied. Two groups of HD patients on standard cuprophane treatment were investigated after an overnight fast. In the first group (mean age 68 +/- 8 years; n = 6) vitamin supplementation was withdrawn two weeks prior to the study, whereas the second group (mean age 73 +/- 3 years; n = 7) continued their normal vitamin intake. The two control groups, one consisting of age-matched subjects (mean age 72 +/- 2 years; n = 21), the other of younger subjects (mean age 36 +/- 7 years; n = 11), were asked to cease vitamin supplementation two weeks before the study and to fast overnight before blood sampling. Serial blood and dialysate samples were collected during HD in the vitamin-deprived patient group, and a single blood sample was collected in the other three groups. Plasma concentrations of vitamin C (total and reduced form), vitamin E (alpha-tocopherol) and malondialdehyde (MDA) were determined with newly adopted and validated HPLC methods. Basal plasma vitamin C concentrations were lower among vitamin-deprived HD patients than among age-matched controls or vitamin-supplemented HD patients (22 +/- 6 microM versus 39 +/- 19 microM and 34 +/- 10 microM, respectively). During a 3-hour HD session, the mean decrease in total vitamin C was 40%. Basal alpha-tocopherol concentrations did not differ significantly between vitamin-deprived HD patients and vitamin-supplemented HD patients or age-matched controls (39 +/- 5 microM versus 40 +/- 11 microM and 38 +/- 6 microM, respectively), but were lower in younger controls (33 +/- 4 microM). No alpha-tocopherol was detected in the dialysate, and its plasma concentration did not change significantly during a single HD session. Basal plasma MDA concentrations were higher in vitamin-supplemented HD patients than in vitamin-deprived HD patients or age-matched controls (1.5 +/- 0.2 microM versus 0.9 +/- 0.2 microM and 1.1 +/- 0.2 microM, respectively). No MDA was detected in the dialysate, and its plasma concentration did not change significantly during a single HD session. Our results indicate an increased need of vitamin C supplementation in HD patients. The concentration of oxidized vitamin C seems to peak early during HD and may be of value as a marker of OFR production. alpha-tocopherol concentrations do not change during HD and do not differ from those in control subjects. MDA may increa

Topics: Adult; Aged; Ascorbic Acid; Biomarkers; Chromatography, High Pressure Liquid; Diet; Female; Free Radicals; Humans; Kidney Diseases; Male; Malondialdehyde; Middle Aged; Renal Dialysis; Reproducibility of Results; Superoxides; Vitamin E

The kinetics of vitamin E was followed in serum, liver and kidney of 10- and 55-day-old rats after the administration of a single i.m. dose of 100 mg alpha-tocopherol acetate/100 g body wt. The basal levels without vitamin E administration were significantly higher in serum and liver of 10- than 55-day-old rats. The effect of vitamin E on cisplatin (CP; 0.6 mg/100 g body wt., i.p.) nephrotoxicity was investigated by determining urinary volume and protein excretion, as well as the concentration of blood urea nitrogen (BUN) and lipid peroxides in renal tissue (LPO). Previously described age differences in CP nephrotoxicity were confirmed. The administration of vitamin E, 12 h prior to CP, diminished the toxic effect of CP in young and adult rats. This effect could not be enhanced by a second administration of vitamin E. The simultaneous administration of vitamin E and C 12 h prior to CP intensified the protective effect of a single administration of vitamin E in 10- and 55-day-old rats without influencing the concentration of platinum in renal tissue.

Topics: Aging; Animals; Antineoplastic Agents; Ascorbic Acid; Blood Urea Nitrogen; Cisplatin; Female; Kidney Diseases; Lipid Peroxides; Male; Platinum; Rats; Rats, Wistar; Vitamin E

The critical organ of chronic cadmium (Cd) exposure are kidneys. Long-term exposure leads to Cd accumulation in kidneys and causes renal tubular dysfunctions. Cd-induced renal changes are irreversible, so the primary prevention by different nutrients can play an important role. In this study, male guinea pigs which, like humans, do not synthetize ascorbic acid (AA) received low (2 mg/animal/day) or high (100 mg/animal/day) dosage of AA and cadmium (1 mg Cd/animal/day) in drinking water for 12 weeks. Characteristic finding in renal morphology of Cd-intoxicated guinea pigs was dilatation of interstitial veins with apparent paravenous lymphatic infiltrates. Histomorphological changes were more evident in Cd-intoxicated guinea pigs with low AA intake. High AA intake apparently reduced in Cd-intoxicated guinea pigs the extent of renal damage. Cadmium significantly increased serum creatinine and urea levels in the group of guinea pigs with low AA intake but not in guinea pigs receiving high concentration of AA. The results showed that AA can be effective in the protection of Cd-induced nephrotoxicity.

Topics: Animals; Ascorbic Acid; Cadmium Poisoning; Dose-Response Relationship, Drug; Guinea Pigs; Kidney; Kidney Diseases; Male

The influence of ascorbic acid (AA, 5 g/kg body weight) on chromate (Cr, 10 mg/kg) induced proteinuria, which is a sensitive parameter of its nephrotoxicity, was investigated in adult female Wistar rats. The concentrations of Cr and ascorbic acid (AA) were determined in renal tissue. Cr nephrotoxicity is related to its intracellular reduction from Cr(VI) to Cr(III). Proteinuria was completely prevented by enhancement of extracellular reduction of Cr(VI) to Cr(III) followed by rapid renal excretion when Cr and AA were given concomitantly. With an interval up to 1 h between Cr and AA, proteinuria was decreased probably by the radical scavenging function of AA. At an interval of 3 h AA enhanced Cr toxicity by increased intracellular Cr reduction. If the interval was increased to 5 h or if Cr was given 24 h after AA, no influence of AA could be detected. Our results confirm that AA is a very effective reductant of Cr which can influence Cr nephrotoxicity in very high concentrations. It depends on the interval between Cr and AA administration whether or not there is a beneficial effect of AA in Cr nephrotoxicity.

Topics: Animals; Ascorbic Acid; Chromates; Female; Kidney; Kidney Diseases; Proteinuria; Rats; Rats, Wistar

4-Aminophenol (PAP) is known to cause nephrotoxicity in the rat where it produces selective necrosis to renal proximal tubules. The aim of this work was to investigate the toxicity of PAP and its known nephrotoxic metabolite 4-amino-3-S-glutathionylphenol using a well defined suspension of rabbit renal proximal tubules. PAP at a concentration of 0.5 mM and 1 mM caused proximal tubule cell death (measured by lactate dehydrogenase release) in a time-dependent manner over a 4-h exposure. In contrast, 4-amino-3-S-glutathionylphenol at 1 mM produced no proximal tubule cell death over a similar 4-h exposure. At 2 h, 1 mM PAP inhibited proximal tubule respiration by 30% and decreased cellular adenosine triphosphate (ATP) levels by 60%. These events preceded cell death. The addition of PAP to proximal tubules led to a rapid depletion of cellular glutathione, exposure to 0.5 mM causing a 50% depletion within 1 h. The cytochrome P-450 inhibitors SKF525A (1 mM) and metyrapone (1 mM), the iron chelator deferoxamine (1 mM) and the antioxidant N,N'-phenyl-1,4-phenylenediamine (2 microM) had no effect on PAP-induced cell death. However ascorbic acid (0.1 mM), afforded a marked protection against the depletion of cellular glutathione and completely protected against the cell death produced by 1 mM-PAP. These results indicate that oxidation of PAP to generate a metabolite that can react with glutathione is an important step in the toxicity, while mitochondria appear to be a critical target for the reactive intermediate formed.

Topics: Adenosine Triphosphate; Aminophenols; Animals; Ascorbic Acid; Cell Death; Energy Metabolism; Female; Glutathione; In Vitro Techniques; Kidney Diseases; Kidney Tubules, Proximal; L-Lactate Dehydrogenase; Mitochondria; Nystatin; Oxygen Consumption; Phenols; Rabbits

Topics: Acute Kidney Injury; Adult; Ascorbic Acid; Biopsy; Calcium Oxalate; Humans; Kidney; Kidney Diseases; Male; Renal Dialysis

4-Aminophenol (p-aminophenol, PAP) causes selective necrosis to the pars recta of the proximal tubule in Fischer 344 rats. The basis for this selective toxicity is not known but PAP can undergo oxidation in a variety of systems to form the 4-aminophenoxy free radical. Oxidation or disproportionation of this radical will form 1,4-benzoquinoneimine which can covalently bind to cellular macromolecules. We have recently reported that a glutathione conjugate of PAP, 4-amino-3-S-glutathionylphenol, is more toxic to the kidney than the parent compound itself. In this study we have examined the distribution and covalent binding of radiolabel from 4-[ring 3H]-aminophenol in the plasma, kidney and liver of rats 24 h after dosing and related these findings to the extent of nephrotoxicity. In addition, we have examined the effect of ascorbic acid which will slow the oxidation of PAP; acivicin, an inhibitor of gamma-glutamyltransferase and hence the processing of glutathione-derived conjugates; and probenecid, an inhibitor of organic anion transport on the nephrotoxicity produced by PAP. Administration of a single dose of PAP at 458 or 687 mumol kg-1 produced a dose-related alteration in renal function within 24 h which was associated with proximal tubular necrosis. The lesion at the lower dose was restricted to the S3 proximal tubules in the medullary rays, while at the higher dose it additionally affected the S3 tubules in the pars recta region of the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminophenols; Animals; Antimetabolites; Ascorbic Acid; Isoxazoles; Kidney; Kidney Diseases; Kidney Function Tests; Liver; Male; Probenecid; Rats; Rats, Inbred F344

A 71-year-old woman was admitted with end-stage renal failure and histological evidence of oxalosis. This case of diffuse renal tubular crystal calcium oxalate deposits seems to be induced by long-term piridoxilate therapy (10 years) or simultaneous intake of both piridoxilate and vitamin C (500 mg/day for 6 months), since no other cause of secondary oxalosis could be found. So, it seems necessary to monitor the serum creatinine level, especially in the elderly, during piridoxilate therapy and to avoid high vitamin C intakes in patients under such treatment to prevent development of renal insufficiency.

Topics: Aged; Angina Pectoris; Ascorbic Acid; Calcium Oxalate; Creatinine; Drug Interactions; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules; Pyridoxine; Time Factors; Vasodilator Agents

Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.

Topics: Animals; Ascorbic Acid; Chromates; Glutathione; Kidney; Kidney Diseases; Male; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Sulfhydryl Compounds

Administration of either 2,5-dichloro-3-(glutathion-S-yl)-1, 4-benzoquinone (DC-[GSyl]BQ) or 2,5,6-trichloro-3-(glutathion-S-yl)-1,4-benzoquinone (TC-[GSyl]BQ) to male Sprague-Dawley rats caused dose-dependent (50-200 mumol/kg; iv) renal proximal tubular necrosis, as evidenced by elevations in blood urea nitrogen (BUN), and in the urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and glucose. Renal proximal tubular necrosis was also confirmed by histological examination of kidney slices prepared from DC-(GSyl)BQ- and TC-(GSyl)BQ-treated animals. Administration of the corresponding hydroquinone conjugates (DC-[GSyl]HQ and TC-[GSyl]HQ), prepared by reducing the quinones with a threefold molar excess of ascorbic acid, resulted in a substantial increase in nephrotoxicity. Moreover, in contrast to other glutathione (GSH)-conjugated hydroquinones, the nephrotoxicity of both DC-(GSyl)HQ and TC-(GSyl)HQ was potentiated when rats were pretreated with AT-125, an irreversible inhibitor of gamma-GT. Neither the quinone-GSH nor the hydroquinone-GSH conjugates caused any effect on liver histology or serum glutamate-pyruvate transaminase levels. The results suggest that coadministration of ascorbic acid with DC-(GSyl)BQ or TC-(GSyl)BQ decreases their interactions with extrarenal nucleophiles, including plasma proteins, and thus increases the concentration of the conjugates delivered to the kidney, and hence toxicity. Furthermore the ability of AT-125 to potentiate the nephrotoxicity of DC-(GSyl)HQ and TC-(GSyl)HQ suggests that metabolism of these conjugates by gamma-GT constitutes a detoxication reaction.

Topics: Animals; Ascorbic Acid; Chloranil; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Synergism; Electrochemistry; gamma-Glutamyltransferase; Glutathione; Isoxazoles; Kidney Cortex; Kidney Diseases; Kidney Tubular Necrosis, Acute; Male; Oxidation-Reduction; Rats; Rats, Inbred Strains

Topics: Anti-Bacterial Agents; Ascorbic Acid; Child; Colonic Diseases; Female; Humans; Kidney Diseases; Malacoplakia; Nutrition Disorders; Parenteral Nutrition; Rectal Diseases

Guinea pigs were maintained for various periods of time on low (0.5 mg/day), intermediate (20 mg/day), or high (100 and 500 mg/day) levels of dietary ascorbic acid. Animals in each experimental group were challenged with Candida albicans via cardiac injection, and the course of infection in the kidneys was assessed. The results show that the animals receiving only 0.5 mg of ascorbic acid per day were significantly more susceptible to the infection than animals maintained on any higher level of dietary ascorbic acid. The greater susceptibility of the guinea pigs in the 0.5-mg level group was evident, however, only during "early" stages of the infection (until about day 3). Guinea pigs receiving high levels of dietary ascorbic acid were no more resistant at any time after infection, or with any challenge dose, than those receiving an intermediate dietary level. Although these data suggest that vitamin C may be involved in resistance to candidiasis, tissue levels of ascorbic acid do not change significantly with time after infection. These results indicate that low levels of dietary ascorbic acid increase susceptibility to candidiasis, yet high (or "megadose") levels of dietary vitamin C do not show any effect on resistance to this microorganism.

Topics: Animals; Ascorbic Acid; Candidiasis; Diet; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Guinea Pigs; Immunity, Innate; Kidney Diseases; Time Factors

The effect of peritoneal dialysis on plasma ascorbate levels was investigated in 32 patients suffering from end-stage renal disease. Our studies demonstrated a high peritoneal clearance of ascorbic acid resulting in a significant loss into the dialysate. The quantity of ascorbic acid lost by patients undergoing peritoneal dialysis was proportional to the predialysis ascorbic acid levels. Since the ascorbic acid lost from the plasma during peritoneal dialysis is not adequately replaced by dietary consumption of vitamin C, patients undergoing chronic peritoneal dialysis should receive ascorbic acid supplementation as an important part of their therapeutic regimen.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis

Topics: Animals; Ascorbic Acid; Glucose; Glycerol; Hematologic Diseases; Kidney Diseases; Rabbits

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Body Burden; Drug Combinations; Evaluation Studies as Topic; Female; Gluconates; Humans; Iodine Radioisotopes; Kidney Diseases; Male; Mercury Radioisotopes; Middle Aged; Pentetic Acid; Radionuclide Imaging; Rats; Technetium; Tissue Distribution

A novel fluorometric method for the determination of uric acid based on the coupled reactions of uric acid with uricase and peroxidase to form highly fluorescent 2,2'dihydroxy-3,3'-dimethoxy-biphenyl-5,5'-diacetic acid is described. The calibration curve was constructed from a series of standard uric acid solutions vs. the corresponding relative fluorescence. It was linear up to 15 mg/dl (0.9 mmol/l). The serum or plasma samples must be deproteinated with (absolute) ethanol before assay and its uric acid content can be obtained from the calibration curve. This method is rather simple, having good precision and accuracy. High level ascorbic acid in the sample falsely elevates uric acid concentration. Comparison of the results obtained on the patient sera with a colorimetric phosphotungstate method and a standard enzymatic spectrophotometric method gave coefficients of correlation of 0.908 and 0.986, respectively.

Topics: Ascorbic Acid; Horseradish Peroxidase; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Renal Dialysis; Spectrometry, Fluorescence; Urate Oxidase; Uric Acid

Topics: Adult; Aged; Amyloidosis; Ascorbic Acid; Biopsy; Female; Humans; Kidney Diseases; Male; Middle Aged; Tuberculosis

Topics: Adult; Ascorbic Acid; Calcinosis; Humans; Kidney Diseases; Male; Oxalates

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Child; Child, Preschool; Creatinine; Female; Glomerular Filtration Rate; Humans; Infant; Iron; Kidney Diseases; Kidney Function Tests; Male; Mice; Mice, Inbred Strains; Middle Aged; Radionuclide Imaging; Technetium; Urea

Topics: Ascorbic Acid; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Iron; Kidney Diseases; Radionuclide Imaging; Technetium

Topics: Anemia, Hemolytic; Anemia, Hypochromic; Ascorbic Acid; Bilirubin; Blood Transfusion; Catalase; Chronic Disease; Glomerulonephritis; Gout; Hemoglobinometry; Humans; Iron; Kidney Diseases; Liver Diseases; Nephritis; Nitrogen; Rheumatic Fever; Surgical Procedures, Operative

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Flavonoids; Humans; Kidney Diseases

Topics: Ascorbic Acid; Blood Proteins; Chromatography; Erythrocytes; Humans; Inulin; Iron; Kidney Diseases; Kidney Function Tests; Protein Binding; Radionuclide Imaging; Technetium

Topics: Ascorbic Acid; Brain Diseases; Humans; Iron; Kidney Diseases; Radionuclide Imaging; Technetium

Topics: Acidosis, Renal Tubular; Adult; Aluminum; Ascorbic Acid; Bone Diseases; Calcium; Calcium Metabolism Disorders; Female; Humans; Hyperparathyroidism; Kidney Diseases; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Osteomalacia; Vitamin D; Vitamin D Deficiency

Topics: Animals; Ascorbic Acid; Blood Urea Nitrogen; Body Fluids; Histocytochemistry; In Vitro Techniques; Kidney; Kidney Diseases; Mercury Poisoning; Organ Size; Rats; Succinate Dehydrogenase; Tetracycline

Topics: Ascorbic Acid; Injections, Intraperitoneal; Kidney Diseases; Kidney Function Tests; Mercury Poisoning; Metabolism; Niobium; Phosphates; Poisons; Rats; Research; Toxicology; Uranium; Urine

Topics: Adenosine Triphosphate; Anemia; Anemia, Hemolytic; Ascorbic Acid; Blood Chemical Analysis; Blood Glucose; Carbon Dioxide; Erythrocyte Count; Erythrocytes; Geriatrics; Glucosephosphate Dehydrogenase; Glutathione; Hemoglobinometry; Hemolysis; Kidney Diseases; Metabolism; Methemoglobinemia; Nucleosides; Pyelonephritis; Renal Insufficiency; Sulfamethizole; Sulfathiazoles; Sulfonamides; Toxicology; Urinary Catheterization

Topics: Ascorbic Acid; Child; Heart Failure; Humans; Infant; Kidney Diseases; Medical Records; Vitamins