8-hydroxy-2--deoxyguanosine and Proteinuria

8-hydroxy-2--deoxyguanosine has been researched along with Proteinuria* in 13 studies

Trials

6 trial(s) available for 8-hydroxy-2--deoxyguanosine and Proteinuria

ArticleYear
Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation.
    Metabolism: clinical and experimental, 2011, Volume: 60, Issue:2

    AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120-treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables-matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R² = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adsorption; Aged; Biomarkers; Carbon; Creatinine; Deoxyguanosine; Disease Progression; Fatty Acid-Binding Proteins; Female; Humans; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Oxides; Proteinuria

2011
Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner.
    Pharmacological research, 2010, Volume: 61, Issue:1

    Since co-administration of ezetimibe, a specific inhibitor of cholesterol absorption into the intestine, has been shown to augment lipid-lowering effects of statins, ezetimibe plus statins is a novel therapeutic strategy for the treatment of dyslipidemia in high-risk patients. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease (CKD). However, effects of co-administration of ezetimibe with statins on renal damage and dysfunction in CKD patients remain unknown. In this study, we examined whether co-administration of ezetimibe with pitavastatin could augment renoprotective properties of pitavastatin in non-diabetic CKD patients with dyslipidemia. Total cholesterol, LDL-cholesterol and triglycerides levels were reduced more by co-administration of ezetimibe (10mg/day) with pitavastatin (2mg/day) (n=10) than by pitavastatin alone (n=10). In addition, ezetimibe plus pitavastatin treatment produced significant incremental reduction in proteinuria related to pitavastatin therapy alone. In univariate analyses, proteinuria was correlated with plasma levels of total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely), asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and urinary excretion levels of L-fatty acid binding protein (L-FABP), a marker of tubular injury and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker. Multiple stepwise regression analysis revealed that LDL-cholesterol (p<0.001) and urinary excretion levels of L-FABP (p=0.001) and 8-OHdG (p<0.001) were independently related to proteinuria (R(2)=0.969). Our present study demonstrated for the first time that co-administration of ezetimibe enhanced proteinuria-lowering effects of pitavastatin in non-diabetic CKD patients partly via a cholesterol-independent manner. Ezetimibe may have pleiotropic actions that could contribute to renoprotective properties of this lipid-lowering agent.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anticholesteremic Agents; Arginine; Azetidines; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Deoxyguanosine; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Fatty Acid-Binding Proteins; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Male; Middle Aged; Proteinuria; Quinolines; Severity of Illness Index; Treatment Outcome; Triglycerides

2010
Comparative effects of benidipine and amlodipine on proteinuria, urinary 8-OHdG, urinary L-FABP, and inflammatory and atherosclerosis markers in early-stage chronic kidney disease.
    The American journal of the medical sciences, 2010, Volume: 339, Issue:2

    We examined the effects of 2 calcium channel blockers, benidipine (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory, oxidative, and atherosclerosis markers in hypertensive patients with mild chronic kidney disease (CKD).. Forty hypertensive patients with CKD were assigned randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for 12 months. Blood pressure, serum creatinine, estimated glomerular filtration rate, urinary protein excretion, urinary liver-type fatty acid-binding protein, interleukin-6, high mobility group box-1 protein, urinary 8-hydroxy-2'-deoxyguanosine, pulse wave velocity, intima-media thickness, and blood asymmetric dimethylarginine were monitored.. Blood pressure decreased equally in both groups (P < 0.001, at 6 and 12 months versus before treatment). Serum creatinine and estimated glomerular filtration rate changed little during the experimental period in each group. However, urinary protein excretion (P < 0.001), urinary liver-type fatty acid-binding protein (P < 0.001), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.001), blood interleukin-6 (P < 0.001), blood high mobility group box-1 (P < 0.05), and pulse wave velocity (P < 0.01) decreased more in group A than in group B with 12 months of treatment. The percent reductions in intima-media thickness and blood asymmetric dimethylarginine were significantly greater in group A than in group B (P < 0.001).. Benidipine is more effective than amlodipine for protecting renal function and potentially for ameliorating atherosclerosis in hypertensive patients with mild CKD. T-type calcium channel blockers may be effective in patients with CKD.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amlodipine; Atherosclerosis; Biomarkers; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Fatty Acid-Binding Proteins; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Proteinuria

2010
Effect of red wine on urinary protein, 8-hydroxydeoxyguanosine, and liver-type fatty acid-binding protein excretion in patients with diabetic nephropathy.
    Metabolism: clinical and experimental, 2009, Volume: 58, Issue:8

    The aim of the present study was to determine whether red or white wine affects urinary protein, 8-hydroxydeoxyguanosine (8-OHdG), and liver-type fatty acid-binding protein (L-FABP) excretion in type 2 diabetic nephropathy patients. Twenty-four type 2 diabetes mellitus patients with nephropathy were randomly allocated to drink a 118-mL (4-oz) glass of red wine (n = 12, group A) or white wine (n = 12, group B) daily for 6 months. Twelve type 2 diabetes mellitus patients with nephropathy who did not drink any wines served as control subjects (group C). Serum creatinine, 24-hour creatinine clearance, hemoglobin A(1c), urinary protein, urinary 8-OHdG, and urinary L-FABP were measured before and 3 and 6 months after the start of the study. In groups A, B, and C, serum creatinine, 24-hour creatinine clearance, and hemoglobin A(1c) changed little during the experimental period. However, urinary protein, 8-OHdG, and L-FABP excretions were significantly decreased at 3 (P < .05) and 6 months (P < .01) compared with the baseline values in group A. In contrast, these markers changed little during the experimental period in groups B and C. Thus, these urinary markers were significantly lower in group A than in groups B and C at 3 and 6 months. These results suggest that red wine is renoprotective whereas white wine has no such effect in type 2 diabetes mellitus patients with nephropathy. The renoprotective effect of red wine may be due in part to its ability to reduce oxidative stress.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antihypertensive Agents; Biomarkers; Deoxyguanosine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Fatty Acid-Binding Proteins; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Oxidative Stress; Proteinuria; Time Factors; Wine

2009
Azelnidipine reduces urinary protein excretion and urinary liver-type fatty acid binding protein in patients with hypertensive chronic kidney disease.
    The American journal of the medical sciences, 2007, Volume: 333, Issue:6

    Hypoxia plays a significant role in the pathogenesis and progression of chronic renal disease. Urinary liver-type fatty acid binding protein (L-FABP) levels reflect the clinical prognosis of chronic renal disease. The calcium channel blocker azelnidipine has anti-oxidative properties and these may contribute to the beneficial effects of this drug. The aim of the present study was to determine whether azelnidipine and/or amlodipine affected urinary protein excretion or the urinary levels of 8-OHdG and L-FABP in hypertensive patients with mild chronic kidney disease (CKD).. Thirty moderately hypertensive chronic kidney disease patients were randomly assigned to 2 treatment groups: azelnidipine 16 mg once daily or amlodipine 5 mg once daily. Treatment was continued for 6 months. Urinary protein excretion and urinary levels of 8-OHdG and urinary L-FABP were measured before 3 and 6 months after the treatment period.. Both drugs exhibited comparable and significant effects on the systolic and diastolic blood pressure. Azelnidipine decreased heart rate significantly after 3 and 6 months whereas amlodipine increased it significantly after 3 and 6 months. Urinary protein excretion, urinary 8-OHdG and urinary L-FABP levels decreased significantly after 3 months (p < 0.05) and 6 months (p < 0.05) in the azelnidipine group. In contrast, amlodipine showed little effect on urinary protein excretion or the urinary levels of 8-OHdG and L-FABP throughout the experimental period.. Azelnidipine is renoprotective in hypertensive patients with mild CKD and this action is, at least in part, due to the anti-oxidative effect.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amlodipine; Antioxidants; Azetidinecarboxylic Acid; Blood Pressure; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Fatty Acid-Binding Proteins; Female; Heart Rate; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Proteinuria

2007
Beneficial effects of olmesartan and temocapril on urinary liver-type fatty acid-binding protein levels in normotensive patients with immunoglobin A nephropathy.
    American journal of hypertension, 2007, Volume: 20, Issue:11

    Liver-type fatty acid-binding protein (L-FABP) is a clinical biomarker of tubulointerstitial damage, which plays an essential role in the progression of chronic kidney disease (CKD), including immunoglobin A (IgA) nephropathy. The effect of combination therapy with the angiotensin receptor blocker (ARB) and the angiotensin-converting enzyme inhibitor (ACEI) on CKD has not been elucidated.. Twenty-four normotensive patients with IgA nephropathy were randomly assigned to receive olmesartan 10 mg/day, temocapril 2 mg/day, or combination therapy with both drugs. Urinary levels of L-FABP as well as 8-hydroxydeoxyguanosine (8-OHdG) and protein excretion were measured before and after 3 months of treatment. The chronicity index and activity index were also assessed by histopathologic findings.. Urinary levels of L-FABP and 8-OHdG were higher in patients with IgA nephropathy than in age-matched and sex-matched healthy controls (122.5 +/- 25.5 v 6.4 +/- 3.8 mug/g.creatinine, P < .001; and 22.6 +/- 4.4 v 4.8 +/- 1.4 ng/mg.creatinine, P < .01, respectively). Urinary levels of L-FABP were correlated with those of 8-OHdG (baseline, P = .0001; after 3 months, P = .008) and the severity of proteinuria (baseline, P = .0015; after 3 months, P = .0001). The percent reductions in urinary levels of L-FABP and 8-OHdG, protein excretion, and activity index after 3 months were greater in the combination therapy group, compared with each monotherapy group of olmesartan (P < .05) and temocapril (P < .05).. The data suggest that a combination therapy of ARB plus ACEI has a greater beneficial effect on renal injury compared with monotherapy using ARB or ACEI in normotensive patients with IgA nephropathy.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Deoxyguanosine; Double-Blind Method; Drug Therapy, Combination; Fatty Acid-Binding Proteins; Female; Glomerulonephritis, IGA; Heart Rate; Humans; Imidazoles; Male; Proteinuria; Tetrazoles; Thiazepines

2007

Other Studies

7 other study(ies) available for 8-hydroxy-2--deoxyguanosine and Proteinuria

ArticleYear
Urinary Polycyclic Aromatic Hydrocarbons in a Longitudinal Cohort of Children with CKD: A Case of Reverse Causation?
    Kidney360, 2022, 06-30, Volume: 3, Issue:6

    Air pollution, which results in the formation of polycyclic aromatic hydrocarbons (PAHs), has been identified as a cause of renal function decline and a contributor to CKD. However, the results of cross-sectional studies investigating personal, integrated biomarkers of PAHs have been mixed. Longitudinal studies may be better suited to evaluate environmental drivers of kidney decline. The purpose of this study was to examine associations of serially measured urinary PAH metabolites with clinical and subclinical measures of kidney function over time among children with CKD.. This study was conducted among 618 participants in the Chronic Kidney Disease in Children study, a cohort study of pediatric patients with CKD from the United States and Canada, between 2005 and 2015. In serially collected urine samples over time, nine PAH metabolites were measured. Clinical outcomes measured annually included eGFR, proteinuria, and BP. Subclinical biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidant stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F. Children were followed over an average (SD) of 3.0 (1.6) years and 2469 study visits (mean±SD, 4.0±1.6). Hydroxynaphthalene (NAP) or hydroxyphenanthrene (PHEN) metabolites were detected in >99% of samples and NAP concentrations were greater than PHEN concentrations. PHEN metabolites, driven by 3-PHEN, were associated with increased eGFR and reduced proteinuria, diastolic BP z-score, and NGAL concentrations over time. However, PAH metabolites were consistently associated with increased KIM-1 and 8-OHdG concentrations.. Among children with CKD, these findings provoke the potential explanation of reverse causation, where renal function affects measured biomarker concentrations, even in the setting of a longitudinal study. Additional work is needed to determine if elevated KIM-1 and 8-OHdG excretion reflects site-specific injury to the proximal tubule mediated by low-grade oxidant stress.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Child; Cohort Studies; Cross-Sectional Studies; Humans; Lipocalin-2; Longitudinal Studies; Oxidants; Polycyclic Aromatic Hydrocarbons; Proteinuria; Renal Insufficiency, Chronic; United States

2022
Combined endothelin a blockade and chlorthalidone treatment in a rat model of metabolic syndrome.
    The Journal of pharmacology and experimental therapeutics, 2014, Volume: 351, Issue:2

    Experiments determined whether the combination of endothelin A (ETA) receptor antagonist [ABT-627, atrasentan; (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid] and a thiazide diuretic (chlorthalidone) would be more effective at lowering blood pressure and reducing renal injury in a rodent model of metabolic syndrome compared with either treatment alone. Male Dahl salt-sensitive rats were fed a high-fat (36% fat), high-salt (4% NaCl) diet for 4 weeks. Separate groups of rats were then treated with vehicle (control), ABT-627 (ABT; 5 mg/kg per day, in drinking water), chlorthalidone (CLTD; 5 mg/kg per day, in drinking water), or both ABT plus CLTD. Mean arterial pressure (MAP) was recorded continuously by telemetry. After 4 weeks, both ABT and CLTD severely attenuated the development of hypertension, whereas the combination further reduced MAP compared with ABT alone. All treatments prevented proteinuria. CLTD and ABT plus CLTD significantly reduced nephrin (a podocyte injury marker) and kidney injury molecule-1 (a tubulointerstitial injury marker) excretion. ABT, with or without CLTD, significantly reduced plasma 8-oxo-2'-deoxyguanosine, a measure of DNA oxidation, whereas CLTD alone had no effect. All treatments suppressed the number of ED1(+) cells (macrophages) in the kidney. Plasma tumor necrosis factor receptors 1 and 2 were reduced only in the combined ABT and CLTD group. These results suggest that ABT and CLTD have antihypertensive and renal-protective effects in a model of metabolic syndrome that are maximally effective when both drugs are administered together. The findings support the hypothesis that combined ETA antagonist and diuretic treatment may provide therapeutic benefit for individuals with metabolic syndrome consuming a Western diet.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Arterial Pressure; Atrasentan; Cell Adhesion Molecules; Chlorthalidone; Deoxyguanosine; Disease Models, Animal; Diuretics; Drug Combinations; Endothelin A Receptor Antagonists; Endothelins; Hypertension; Inflammation; Kidney Diseases; Male; Membrane Proteins; Metabolic Syndrome; Oxidative Stress; Proteinuria; Pyrrolidines; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Receptor, Endothelin A; Sodium Chloride, Dietary

2014
[Salt intake and the progression of renal failure in patients with chronic kidney disease].
    Nihon Jinzo Gakkai shi, 2010, Volume: 52, Issue:7

    Salt intake not only elevates the levels of blood pressure, glomerular capillary pressure and proteinuria, but also increases oxidative stress within the renal cortex in animal models. We examined the effect of salt intake on the rate of renal function decline, urinary protein and oxidative stress in patients with chronic kidney disease (CKD).. Clinical data including systolic blood pressure (SBP)and diastolic blood pressure (DBP), serum creatinine, uric acid, total cholesterol, triglyceride, urinary protein, salt intake, protein intake of non-diabetic CKD 53 patients were observed for one year. At the end of the observation period, we measured 8-hydroxydeoxy guanosine (8-OHdG) in spot urine. We calculated the slope of reciprocal serum creatinine as the rate of renal function decline (delta1/Cr). We then investigated the relationship between those clinical factors and delta1/Cr, and urinary 8-OHdG, and also selected clinical factors that significantly influence delta1/Cr and urinary 8-OHdG by stepwise multiple regression analysis. In addition, we investigated the gender difference in urinary 8-OHdG.. Annual mean SBP and DBP of all patients were 121.5 +/- 9.3 mmHg and 72.5+/- 6.2 mmHg, respectively. delta1/Cr was negatively correlated with salt intake, urinary protein and urinary protein was a significant predictor of delta1/Cr in a multiple regression analysis. Salt intake was positively correlated with protein intake and urinary protein. Urinary 8-OHdG of all patients was positively correlated with urinary protein and it was a significant predictor. Urinary 8-OHdG of male patients was positively correlated with salt intake and was a significant predictor; in female patients, it was positively correlated with urinary protein and total cholesterol and these two factors were significant predictors.. Salt intake increases urinary protein and promotes the progression of renal failure in CKD patients.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chronic Disease; Deoxyguanosine; Disease Progression; Humans; Kidney Diseases; Male; Middle Aged; Oxidative Stress; Proteinuria; Regression Analysis; Renal Insufficiency; Sodium Chloride, Dietary

2010
Taurine administration after appearance of proteinuria retards progression of diabetic nephropathy in rats.
    The Kobe journal of medical sciences, 2008, May-23, Volume: 54, Issue:1

    Oxidative stress has been postulated to be involved in the development of diabetic nephropathy. In the present study, we evaluated the effect of taurine, an endogenous antioxidant, on diabetic nephropathy by mixing it with the daily drinking water (1%w/v) of streptozotocin-induced diabetic rats from the beginning of the fourth month after the induction of diabetes, during which the urinary protein excretion in untreated diabetic rats showed significant increase in comparison with nondiabetic rats. The taurine administration significantly suppressed further increase in urinary protein excretion in diabetic rats, accompanied by the reduction of mesangial extracellular matrix expansion and TGF-beta expression in the renal glomerulus. Immunohistochemical study showed that taurine administration suppressed the intensified stainings to the three different types of oxidative stress markers, such as 8-hydroxyl-2'-deoxyguanosine (8-OHdG), pentosidine, and nitrotyrosine observed in the renal tissues of untreated diabetic rats. These findings suggest that taurine has the ability to suppress the progression of diabetic nephropathy at least in part by its antioxidant property. Since this beneficial effect of taurine was obtained even if its administration was started after the time point when urinary protein excretion already became apparently higher than that of age-matched nondiabetic animals, taurine administration was potentially expected to be applied in clinical field to retard the development of nephropathy in diagnosed diabetic patients.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; Blood Glucose; Body Weight; Deoxyguanosine; Diabetic Nephropathies; Disease Progression; Glycated Hemoglobin; Immunohistochemistry; Male; Oxidative Stress; Proteinuria; Rats; Rats, Sprague-Dawley; Taurine; Tyrosine

2008
Protective effects of keishibukuryogan on the kidney of spontaneously diabetic WBN/Kob rats.
    Journal of ethnopharmacology, 2007, Mar-21, Volume: 110, Issue:2

    Keishibukuryogan, one of the traditional herbal formulations, is used clinically to improve blood circulation. It consists of the following five crude drugs: Cinnamomi Cortex, Poria, Moutan Cortex, Persicae Semen and Paeoniae Radix. In this study, the effects of keishibukuryogan against renal damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of keishibukuryogan significantly attenuated urinary protein excretion and serum creatinine levels. It did not affect body weight loss and blood glucose levels, but it suppressed renal and hepatic weights of WBN/Kob rats. Keishibukuryogan also reduced fibronectin and transforming growth factor beta(1) (TGF-beta(1)) protein expression in the renal cortex. Furthermore, lipid peroxidation levels in both kidney and liver were significantly lower than those of untreated control WBN/Kob rats. Urinary excretion of 8-hydroxy-deoxyguanosine was suppressed by keishibukuryogan treatment. These results suggest that keishibukuryogan reduces oxidative stress by hyperglycemia, and that it protects renal function and suppresses fibronectin deposition induced by TGF-beta(1) production in WBN/Kob rats.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Creatinine; Deoxyguanosine; Diabetes Mellitus, Experimental; Drugs, Chinese Herbal; Fibronectins; Hyperglycemia; Kidney; Lipid Peroxidation; Male; Medicine, Traditional; Organ Size; Oxidative Stress; Phytotherapy; Plant Preparations; Protective Agents; Proteinuria; Rats; Rats, Wistar; Transforming Growth Factor beta1; Weight Loss

2007
Effect of a novel free radical scavenger, edaravone, on puromycin aminonucleoside induced nephrosis in rats.
    Pediatric nephrology (Berlin, Germany), 2005, Volume: 20, Issue:10

    Recent studies indicate that excessive production of oxidants plays a role in the pathogenesis of glomerular injury leading to proteinuria in patients with minimal-change nephrotic syndrome (MCNS). The novel free radical scavenger, edaravone (EDA), which was recently developed in Japan, is currently used in patients with stroke. We studied whether this new agent would be beneficial in patients with MCNS by its antioxidant activity and examined its effect on proteinuria in nephrosis induced by puromycin-aminonucleoside (PAN) in rats. Nineteen Wistar-Kyoto rats injected with PAN were assigned to four groups: group 1, without EDA (n=4); group 2, concomitant EDA injection from 1 day prior to PAN administration (n=5); group 3, concomitant EDA injection from 1 day after PAN administration (n=5); group 4, concomitant EDA injection from 3 days after PAN administration (n=5). Daily urinary excretions of protein and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a new sensitive marker of oxidative DNA damage in vivo, were measured in each group from the 1st to the 30th day after PAN injection. In group 1 proteinuria developed from the 5th day and reached the peak level on the 9th day. In groups 2, 3, and 4 proteinuria did not appear until the 6th day. The excretions in urinary protein and 8-OHdG were significantly lower in groups 2, 3, and 4 than group 1 on days 5, 9, and 25. In conclusion, EDA could delay and ameliorate the urinary protein excretion in accordance with the urinary 8-OHdG excretion in PAN-induced nephrosis.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antipyrine; Biomarkers; Deoxyguanosine; DNA Damage; Edaravone; Female; Free Radical Scavengers; Nephrosis; Oxidation-Reduction; Proteinuria; Puromycin Aminonucleoside; Rats; Rats, Inbred WKY; Time Factors

2005
The meaning of serum levels of advanced glycosylation end products in diabetic nephropathy.
    Metabolism: clinical and experimental, 2000, Volume: 49, Issue:8

    It has been reported that advanced glycosylation end products (AGEs) play an important role in the development of diabetic complications. To evaluate the relationship between serum AGEs and diabetic nephropathy, we measured serum AGE levels in diabetic patients with normoalbuminuria (N), microalbuminuria (M), overt proteinuria (O), and hemodialysis (HD), non diabetic patients with nephropathy, and age-matched control subjects using the enzyme-linked immunosorbent assay (ELISA). Urine AGE levels were also measured in these subjects except group HD. Serum AGE levels in diabetic patients were not significantly higher than those in the normal subjects. When we compared serum AGE levels among various stages of diabetic nephropathy, groups O and HD had significantly higher serum AGE levels than the other groups. Serum AGE levels in group HD were almost 6-fold higher than those in groups N and M. In contrast, there were no significant differences in urinary AGE levels among any diabetic groups. As for the variables that determine serum AGE levels in diabetic patients, there was no significant correlation between serum AGEs and fasting blood glucose, hemoglobin A1c (HbA1c), or duration of diabetes. In contrast, serum AGEs showed a strong correlation with serum creatinine and an inverse correlation with creatinine clearance. To evaluate the relationship between serum AGEs and oxidative stress in diabetic nephropathy, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde (MDA), which are biological markers of total oxidative stress in vivo, were also examined. Both urinary 8-OHdG and serum MDA levels were significantly higher in diabetic patients with proteinuria versus those without proteinuria. However, there was no significant correlation between serum AGEs and urinary 8-OHdG or serum MDA levels in diabetic patients. These results suggest that the accumulation of serum AGEs in diabetic nephropathy may be mainly due to decreased removal in the kidney rather than increased production by high glucose levels or oxidative stress.

    Topics: 8-Hydroxy-2'-Deoxyguanosine; Albuminuria; Deoxyguanosine; Diabetes Mellitus; Diabetic Nephropathies; Female; Glycation End Products, Advanced; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Proteinuria; Renal Dialysis

2000