ascorbic-acid and Liver-Cirrhosis

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.

Topics: Ascorbic Acid; Carcinoma, Hepatocellular; Collagen; Free Radicals; Hemochromatosis; Humans; Iron; Liver; Liver Cirrhosis; Liver Neoplasms; Lysosomes; Membrane Potentials; Porphyrias; Potassium; Transferrin; Uroporphyrins; Vitamin E

Topics: Acute Disease; Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Chronic Disease; Fatty Liver; Humans; Hypercholesterolemia; Lipid Metabolism; Liver Cirrhosis; Scurvy

Topics: Amino Acids; Ascorbic Acid; Biological Transport; Diet; Digestion; Female; Ferritins; Gastric Juice; Hemoglobins; Humans; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Iron; Iron Radioisotopes; Liver Cirrhosis; Male; Menopause; Menstruation; Models, Biological; Pancreas; Pregnancy

To assess the effects of combined vitamin therapy on oxidant-antioxidant hepatic status and hemoglobin (Hb) derivatives on β-thalassemia major (β-TM), a prospective study of 60 β-TM patients aged 4 to 17 years, was conducted. Thirty-nine patients with initial low serum vitamins E, C and A, were treated with oral combined vitamins for 1 year compared to 21 patients with normal vitamin levels. Serum transaminases, serum ferritin, hepatic fibroscan elastography (TE) and magnetic resonance imaging R2* (MRI R2*) for liver iron concentration (LIC), were assessed before and after 6 and 12 months of therapy. Antioxidant capacity was assessed by levels of reduced glutathione (GSH), malondialdehyde (MDA), catalase, superoxide dismutase and GSH enzymes. The studied vitamins, reduced GSH and Hb levels were significantly elevated and paralleled by progressive decline in MDA and ferritin during therapy (p <0.001). Serum transaminase and superoxide dismutase were significantly decreased, while GSH reductase was significantly elevated during therapy (p <0.001). Improvement of hepatic fibrosis as 23.0% had TE (>12 kPa) at baseline compared to 20.5% after therapy (p >0.05), although LIC values were significantly decreased (p <0.001). Combined vitamin therapy improves the antioxidant/oxidant balance, LIC and hepatic fibrosis in young β-TM patients.

Topics: Adolescent; Antioxidants; Ascorbic Acid; beta-Thalassemia; Child; Child, Preschool; Female; Ferritins; Glutathione; Humans; Liver; Liver Cirrhosis; Male; Malondialdehyde; Prospective Studies; Superoxide Dismutase; Transaminases; Vitamin A; Vitamin E

Patients with cirrhosis show intrahepatic endothelial dysfunction, characterized by an impaired flow-dependent vasorelaxation. This alteration is responsible for the marked postprandial increase in portal pressure and is attributed to an insufficient release of nitric oxide (NO). Ascorbic acid reverts endothelial dysfunction in other vascular disorders, via the increase of NO bioavailability through the neutralization of superoxide anions, thus preventing the scavenging of NO by superoxide. This study examined whether acute ascorbic acid administration might improve endothelial dysfunction in cirrhosis. Thirty-seven portal hypertensive patients with cirrhosis had measurements of hepatic and systemic hemodynamics, ascorbic acid, and malondialdehyde (MDA). Patients were randomly allocated to receive ascorbic acid (3 g, intravenously, n = 15) or placebo (n = 12) followed by a liquid meal. A third group received ascorbic acid followed by a sham meal (n = 10). Measurements were repeated after 30 minutes (hepatic venous pressure gradient at 15 and 30 minutes). Patients with cirrhosis had significantly lower ascorbic acid levels and higher MDA than healthy controls. Ascorbic acid significantly reduced MDA levels and markedly attenuated the postprandial increase in the hepatic venous pressure gradient (4% +/- 7% vs. 18% +/- 10% in placebo at 30 minutes, P < .001). Ascorbic acid followed by sham meal did not modify hepatic or systemic hemodynamics. In conclusion, patients with cirrhosis exhibited intrahepatic endothelial dysfunction, associated with decreased levels of ascorbic acid and increased levels of MDA. Ascorbic acid improved intrahepatic endothelial dysfunction, blunting the postprandial increase in portal pressure. These results encourage the performance of further studies testing antioxidants as adjunctive therapy in the treatment of portal hypertension.

Topics: Aged; Antioxidants; Ascorbic Acid; Double-Blind Method; Endothelium; Female; Hemodynamics; Humans; Hypertension, Portal; Liver Circulation; Liver Cirrhosis; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Oxidative Stress; Postprandial Period; Splanchnic Circulation; Superoxides

Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease. Although usually indolent, this disease can progress to cirrhosis in some patients. There is currently no proven medical therapy for the treatment of NASH. The aim of our study was to evaluate the efficacy of combination alpha-tocopherol (vitamin E) and vitamin C in reducing histologic inflammation and fibrosis.. This was a prospective, double-blind, randomized, placebo-controlled trial with a total enrollment of 49 patients; 45 patients completed the study. All patients were randomized to receive either vitamins E and C (1000 IU and 1000 mg, respectively) or placebo daily for 6 months, based on their initial histologic diagnosis of NASH. Additionally, all patients were given standard weight-loss counseling and encouraged to follow a low fat diet (<30 fat g/day). The pre- and posttreatment liver biopsies were reviewed by a single pathologist, who was blinded to the patient's medication. Biopsies were scored based on a modification of the scoring system published by Brunt et al. (Am J Gastroenterol 1999;94:2467-74). A score of 0-4 was possible for fibrosis, and a score of 0-6 was possible for inflammation and hepatocyte degeneration and necrosis. In addition, body mass index, glycohemoglobin, lipids, and liver enzymes were followed throughout the study.. Forty-five patients completed 6 months of therapy without significant side effects. Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in the doses used in this study, were well tolerated and were effective in improving fibrosis scores in NASH patients. No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy. A larger, multicenter, longer-term trial with vitamin E and vitamin C seems to be warranted.

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Biopsy, Needle; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fatty Liver; Female; Follow-Up Studies; Humans; Liver Cirrhosis; Male; Middle Aged; Probability; Prospective Studies; Reference Values; Severity of Illness Index; Treatment Outcome; Vitamin E

The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.

Topics: Antioxidants; Ascorbic Acid; Humans; Lipid Peroxidation; Liver; Liver Cirrhosis; Malondialdehyde; Postoperative Complications; Prothrombin Time; Reperfusion Injury; Temperature; Thiobarbituric Acid Reactive Substances; Time Factors; Transaminases; Vitamin E

The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver.

Topics: Adenosine Triphosphate; Aged; Ascorbic Acid; Cytochrome P-450 Enzyme System; Enzyme Activation; Female; Glucaric Acid; Humans; Indocyanine Green; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged

Topics: Adult; Aged; Ascorbic Acid; Blood Proteins; Clinical Trials as Topic; Folic Acid; Hepatitis; Humans; Liver Cirrhosis; Liver Diseases; Middle Aged; Nicotinic Acids; Vitamin B 12

We wished to understand the metabolic reprogramming underlying liver fibrosis progression in mice. Administration to male C57BL/6J mice of the hepatotoxins carbon tetrachloride (CCl4), thioacetamide (TAA), or a 60% high-fat diet, choline-deficient, amino-acid-defined diet (HF-CDAA) was conducted using standard protocols. Livers collected at different times were analyzed by gas chromatography-mass spectrometry-based metabolomics. RNA was extracted from liver and assayed by qRT-PCR for mRNA expression of 11 genes potentially involved in the synthesis of ascorbic acid from hexoses,

Topics: Aldehyde Reductase; Animals; Ascorbic Acid; Collagen; Diet, High-Fat; Fructose; Galactose; Glucose; Glucuronates; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL

This study aimed to investigate the association between serum vitamin C and liver fibrosis in patients with NAFLD in the US adults.. We conducted a cross-sectional analysis of data from the 2017 to 2018 cycle of National Health and Nutrition Examination Survey (NHANES). Serum vitamin C and transient elastography (TE)-accessed liver stiffness was taken as independent and dependent variables, respectively. Liver steatosis and fibrosis were detected by controlling attenuation parameter (CAP) and TE. NAFLD was defined by a CAP score of ≥248 dB/m without any indication of other causes of chronic liver disease. The median liver stiffness of ≥8.2 kPa was used to identify significant fibrosis (≥F2) among NAFLD patients. We calculated the adjusted odds ratio (OR) and 95% confidential intervals (CIs) for associations with significant NAFLD fibrosis using multivariable logistic regression models.. Overall, 1926 individuals with NAFLD were included in the analysis and 267 subjects met the definition of significant fibrosis. Serum vitamin C was associated with lower odds of liver fibrosis in NAFLD after adjusting for potential confounders (OR = 0.60, 95% CI, 0.43-0.84), while in the subgroup analysis stratified by gender and body mass index (BMI), this association showed a difference after adjusting for confounders (males: OR = 0.43, 95% CI, 0.26-0.71; females: OR = 0.78, 95% CI, 0.49-1.24). There were no significant associations of serum vitamin C with liver fibrosis in NAFLD with underweight or normal (OR = 1.34, 95% CI, 0.19-9.34).. This cross-sectional study indicated an association of serum vitamin C with significant fibrosis in men and overweight or obese patients with NAFLD.

Topics: Adult; Ascorbic Acid; Cross-Sectional Studies; Elasticity Imaging Techniques; Female; Humans; Liver; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Nutrition Surveys

The purpose of this study was to investigate the effect of vitamin C combined with growth inhibitors on serum miR-130a, nitric oxide (NO), and hemostasis in the treatment of upper gastrointestinal bleeding (UGIB) in cirrhosis. Eighty patients with cirrhosis UGIB treated in our hospital from March 2021 to March 2022 were selected and divided into two groups using the random number table method. The control group received growth inhibitor treatment, while the observation group was given vitamin C combined with growth inhibitor treatment for 3 d. The hemostatic effect, serum laboratory indexes (miR-130a, NO), liver function indexes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), adverse effects, and 24 h hemostasis rate were compared between the two groups. The hemostasis time in the observation group was shorter than that in the control group, and the blood transfusion volume was lower than that in the control group. There was no statistical difference regarding the portal blood flow, miR-130a, NO, AST, and ALT indexes between the two groups before treatment. After treatment, the portal blood flow, miR-130a, NO, AST, and ALT indexes in both groups were lower than those before treatment, and all of them were lower in the observation group than in the control group. Adverse reactions showed no significant difference between the two groups of patients with cirrhosis UGIB,, while the 24 h hemostasis rate in the observation group (97.50%) was significantly higher than that in the control group (77.50%). Vitamin C combined with growth inhibitor was effective in the treatment of cirrhotic UGIB, which could effectively shorten the hemostasis time, reduce the transfusion volume and portal blood flow, and improve miR-130a, NO, and liver function levels of patients, with higher safety, and is worthy of clinical promotion.

Topics: Ascorbic Acid; Gastrointestinal Hemorrhage; Growth Inhibitors; Humans; Liver Cirrhosis; MicroRNAs

Liver fibrosis is characterized by the accumulation of extracellular matrix proteins, mainly composed of collagen. Hepatic stellate cells (HSCs) mediate liver fibrosis by secreting collagen. Vitamin C (ascorbic acid) is a cofactor of prolyl-hydroxylases that modify newly synthesized collagen on the route for secretion. Unlike most animals, humans cannot synthesize ascorbic acid and its role in liver fibrosis remains unclear. Here, we determined the effect of ascorbic acid and prolyl-hydroxylase inhibition on collagen production and secretion by human HSCs. Primary human HSCs (p-hHSCs) and the human HSCscell line LX-2 were treated with ascorbic acid, transforming growth factor-beta (TGFβ) and/or the pan-hydroxylase inhibitor dimethyloxalylglycine (DMOG). Expression of collagen-I was analyzed by RT-qPCR (COL1A1), Western blotting, and immunofluorescence microscopy. Collagen secretion was determined in the medium by Western blotting for collagen-I and by HPLC for hydroxyproline concentrations. Expression of solute carrier family 23 members 1 and 2 (SLC23A1/SLC23A2), encoding sodium-dependent vitamin C transporters 1 and 2 (SVCT1/SVCT2) was quantified in healthy and cirrhotic human tissue. In the absence of ascorbic acid, collagen-I accumulated intracellularly in p-hHSCs and LX-2 cells, which was potentiated by TGFβ. Ascorbic acid co-treatment strongly promoted collagen-I excretion and enhanced extracellular hydroxyproline concentrations, without affecting collagen-I (COL1A1) mRNA levels. DMOG inhibited collagen-I release even in the presence of ascorbic acid and suppressed COL1A1 and alpha-smooth muscle actin (αSMA/ACTA2) mRNA levels, also under hypoxic conditions. Hepatocytes express both ascorbic acid transporters, while p-hHSCs and LX-2 express the only SVCT2, which is selectively enhanced in cirrhotic livers. Human HSCs rely on ascorbic acid for the efficient secretion of collagen-I, which can be effectively blocked by hydroxylase antagonists, revealing new therapeutic targets to treat liver fibrosis.

Topics: Actins; Amino Acids, Dicarboxylic; Animals; Ascorbic Acid; Cell Line; Cells, Cultured; Collagen Type I; Collagen Type I, alpha 1 Chain; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Prolyl-Hydroxylase Inhibitors; Rats; Sodium-Coupled Vitamin C Transporters; Transforming Growth Factor beta

Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. These findings were associated with necroinflammatory, fibrogenic, and pro-oxidant activity via the NADPH oxidase 4. Inhibition of AGEs or RAGE deletion in hepatocytes in vivo reversed these effects. We demonstrate that dysregulation of NRF2 by neddylation of cullin 3 was linked to AGER1 downregulation and that induction of NRF2 using an adeno-associated virus-mediated approach in hepatocytes in vivo reversed AGER1 downregulation, lowered the level of AGEs, and improved proinflammatory and fibrogenic responses in mice on a high AGEs diet. In patients with NASH and diabetes or insulin resistance, low AGER1 levels were associated with hepatocyte ballooning degeneration and ductular reaction. Collectively, prolonged exposure to AGEs in the liver promotes an AGER1/RAGE imbalance and consequent redox, inflammatory, and fibrogenic activity in NASH.

Topics: Animals; Ascorbic Acid; Cholecalciferol; Dehydroepiandrosterone; Diabetes Mellitus, Type 2; Disease Models, Animal; Down-Regulation; Hepatocytes; Liver Cirrhosis; Mice; Mice, Knockout; NF-E2-Related Factor 2; Nicotinic Acids; Non-alcoholic Fatty Liver Disease; Plant Extracts; Receptor for Advanced Glycation End Products

The safety of bowel-cleansing agents is an important issue in clinical practice, especially in patients with chronic diseases. Although the safety and efficacy of polyethylene glycol (PEG) has been investigated in many studies, few studies on PEG plus ascorbic acid exist. In this study, we compared the safety of 2 bowel-cleansing agents for patients with liver cirrhosis: 2-liter PEG (2 L PEG) plus ascorbic acid versus 4-liter PEG (4 L PEG). We performed a retrospective study on colonoscopy in patients with liver cirrhosis. Patients referred for colonoscopy were divided into 2 groups: 2 L PEG plus ascorbic acid (n = 105) and 4 L PEG (n = 61). Safety was assessed by comparing the clinical factors and laboratory findings as follows: blood biochemistry, electrolytes, weight change, and bowel-cleansing quality. Serum electrolytes, laboratory findings, and body weight showed no significant change between the 2 groups. There was no significant change in clinical factors before and after bowel preparation in the PEG group or the PEG plus ascorbic acid group. The acceptability and compliance of patients was better in the 2 L PEG plus ascorbic acid than the 4 L PEG group. In subgroup analysis, patients with compensated or decompensated cirrhosis showed no increased risk of electrolyte imbalances after bowel preparation. Child-Pugh scores did not influence the outcome after bowel cleansing. Successful cleansing was mostly achieved in both groups. Our analysis showed that of the use of 2 L PEG plus ascorbic acid could be a safe choice for colonoscopy in patients with liver cirrhosis.

Topics: Ascorbic Acid; Cathartics; Colonoscopy; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Polyethylene Glycols; Retrospective Studies

We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis, and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28 d or 92 d. RNA-Seq, ChIP-Seq (2 h), and 28 d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92 d. Additional vehicle and 30 µg/kg treatment groups were allowed to recover for 36 d following the 92-d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92 days, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1β, -2, -4, -6, and -10, as well as TNF-α and IFN-γ, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. In summary, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.

Topics: Animals; Ascorbic Acid; Cellular Reprogramming; Chemical and Drug Induced Liver Injury; Collagen; Cytokines; Dose-Response Relationship, Drug; Energy Metabolism; Extracellular Matrix; Female; Gene Expression Regulation; Glucose; Glycogen; Inflammation Mediators; Liver; Liver Cirrhosis; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Polychlorinated Dibenzodioxins; Proline; Time Factors; Transcriptome

Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury.

Topics: Animals; Ascorbic Acid; Cell Line; Cholestasis; Cytoprotection; Hepatocytes; Humans; Lithocholic Acid; Liver; Liver Cirrhosis; Male; Mice; Mice, Knockout; Reactive Oxygen Species

to examine the relationship between the antioxidant potential and severity parameters of cirrhosis in humans.. fifteen patients with hepatic cirrhosis (nine subjects - Child group B, and six subjects - Child group C) and nine control subjects were enrolled in the study. The main criteria taken into account to characterize the diagnosis of cirrhosis and its complications were the AST: ALT ratio, AST to platelet ratio index, Bonacini score, Meld score and Child classification. Those parameters were determined based on laboratory results and patient's clinical records. Se, Zn, ascorbic acid (AA) levels and oxidative stress parameters were measured in blood samples of cirrhotic patients.. the analysis of plasma levels of Se and AA showed low concentrations in cirrhotic patients compared with control subjects (P < 0.05). Though, there was a positive correlation between plasma of Se and severity parameters of cirrhosis in patients of Child group B and C. In the activity of the antioxidant enzymes only catalase was lower in patients of Child group C compared with control group.. we found low plasma levels of Se and AA among cirrhotic patients. However, is not clear why selenium levels tend to increase with the severity of liver cirrhosis.. Introducción/Objetivos: examinar la relación entre los potenciales antioxidantes y los parámetros de gravedad de la cirrosis en los seres humanos. Métodos: quince pacientes con cirrosis hepática (nueve sujetos - grupo Child B, y seis sujetos - grupo Child C) y nueve sujetos control fueron incluidos en el estudio. Los principales criterios que se tuvieron en cuenta para caracterizar el diagnóstico de la cirrosis y sus complicaciones fueron la AST: relación de ALT, AST índice de la relación de plaquetas, clasificación Bonacini, clasificación MELD y clasificación de Child. Estos parámetros fueron determinados con base en los resultados de laboratorio y los registros clínicos del paciente. Se midieron los niveles de Zn, ácido ascórbico (AA) y los parámetros de estrés oxidativo en muestras de sangre de pacientes cirróticos. Resultados: el análisis de los niveles plasmáticos de Se y AA mostraron bajas concentraciones en los pacientes cirróticos en comparación con los sujetos control (P < 0,05); sin embargo, hubo una correlación positiva entre el plasma de Se y los parámetros de gravedad de la cirrosis en pacientes del grupo Child B y C. En la actividad de las enzimas antioxidantes catalasa solamente fue menor en los pacientes del grupo Child C, en comparación con el grupo control. Conclusión: se encontraron niveles bajos en plasma de Se y AA en pacientes cirróticos. Sin embargo, no está claro por qué los niveles de selenio tienden a aumentar con la gravedad de la cirrosis hepática.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Female; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Oxidative Stress; Selenium

Given the involvement of oxidative stress in liver-disease- or hepato-toxicant-induced hepatic damage and fibrosis, antioxidants are an effective preventive and therapeutic tool. The beneficial results of vitamin C, one of the physiological antioxidants, have been observed both in experimental animals and in humans. However, most of these studies have been concerned with supplementary vitamin C; the effects of under vitamin C insufficiency, which humans sometimes confront, have not been substantially investigated. In the present study, we established a vitamin C-insufficient animal model (half-to-normal serum vitamin C concentration) with gulo(-/-) mice that cannot synthesize vitamin C, and induced hepatotoxicity by means of thioacetamide (TAA) injections twice a week for 18 weeks. Additionally, we explored the direct effects of vitamin C both on immortalized human hepatic stellate LX-2 cells and on rat primary hepatic stellate cells. Vitamin C insufficiency resulted in a decreased survival rate and increased serum markers for hepatocyte damage, such as alanine aminotransferase and aspartate aminotransferase. Concomitantly, the levels of reactive oxygen species (ROS) and lipid peroxides in the liver were increased. Histological examinations of the vitamin C-insufficient liver revealed increases in collagen fiber deposition and activated-hepatic-stellate-cell number. Vitamin C, when directly applied to the LX-2 cells as well as the rat primary hepatic stellate cells, suppressed not only proliferation but hydrogen peroxide-induced collagen expression as well. In conclusion, vitamin C insufficiency exacerbated TAA-induced hepatotoxicity. These effects seem to be mainly from insufficient scavenging of ROS in the liver, and possibly in part, by directly affecting hepatic stellate cells.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Collagen; Gene Expression; Hepatic Stellate Cells; Humans; L-Gulonolactone Oxidase; Lipid Peroxidation; Liver Cirrhosis; Male; Mice; Mice, Knockout; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thioacetamide

This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl(4))-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl(4)-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl(4).Then, CCl(4) administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl(4) exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases.

Topics: Animals; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Chronic Disease; Cytoprotection; Ferrous Compounds; Fluorocarbons; Glycyrrhetinic Acid; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Picrates; RNA, Messenger; Up-Regulation

To investigate the efficacy of combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) in reducing ethanol-induced hepatotoxicity.. Rats were maintained for 90 days and grouped as follows: I-control rats, II-ethanol, III-alpha-tocopherol, IV-ethanol+alpha-tocopherol, V-AA, VI-ethanol+ascorbic acid, VII-alpha-tocopherol+ascorbic acid, VIII-ethanol+alpha-tocopherol+ascorbic acid. At the end of the experimental period, markers of hepatic function, oxidative stress, and the expression of markers of inflammation and fibrosis were assayed.. The markers of hepatic function, lipid peroxidation products, protein carbonyls, and the expression of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, cytochrome P4502E1, and collagen Type I were elevated after ethanol administration. All these parameters were reduced in the ethanol group administered AT and AA in combination. The activities of antioxidant enzymes which were reduced by ethanol administration were enhanced on combined administration of AT and AA. The reduction in hepatic fibrosis was almost 20% more in AT and AA co-administered group compared with AT and AA alone treated groups.. Combined administration of fat soluble AT and water soluble AA was beneficial against ethanol-induced hepatotoxicity. This may be due to their different subcellular localizations.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Biomarkers; Chromatography, High Pressure Liquid; Collagen Type I; Drug Therapy, Combination; Ethanol; Inflammation; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Transforming Growth Factor alpha; Tumor Necrosis Factor-alpha

We evaluated the long-term effects of green tea extract (GTE) supplementation on oxidative stress, biliary acute phase protein expression, and liver function in CCl(4)-induced chronic liver injury.. We evaluated the antioxidant activity of GTE in comparison with those of vitamin C, vitamin E, and β-carotene in vitro by using an ultrasensitive chemiluminescence analyzer. Chronic liver injury was induced by intraperitoneally administering carbon tetrachloride (CCl(4)) (1 mL/kg body weight, twice weekly) to female Wistar rats for 8 weeks. The effects of low (4 mg/kg body weight per day) and high (20 mg/kg body weight per day) doses of intragastric GTE on CCl(4)-induced liver dysfunction and fibrosis were examined by measuring the bile and blood reactive oxygen species levels and biochemical parameters by using Western blot and two-dimensional polyacrylamide gel electrophoresis techniques.. GTE has greater scavenging activity against O(2)(-), H(2)O(2), and Hypochlorous acid (HOCl) in vitro than vitamin C, vitamin E, and β-carotene do. In vivo, CCl(4) markedly increased bile and blood reactive oxygen species production, lipid accumulation, number of infiltrated leukocytes, fibrosis, hepatic hydroxyproline content, and plasma alanine aminotransferase and aspartate aminotransferase activities, and reduced plasma albumin levels. Two-dimensional polyacrylamide gel electrophoresis revealed that CCl(4) increased the acute-phase expression of six biliary proteins and decreased hepatic B-cell lymphoma 2 (Bcl-2), catalase, and CuZn superoxide dismutase protein expression. GTE supplementation attenuated CCl(4)-enhanced oxidative stress, levels of biochemical parameters, pathology, and acute-phase protein secretion, and preserved antioxidant/antiapoptotic protein expression.. GTE supplementation attenuates CCl(4)-induced hepatic oxidative stress, fibrosis, acute phase protein excretion, and hepatic dysfunction via the antioxidant and antiapoptotic defense mechanisms.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; beta Carotene; Bile; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury, Chronic; Female; Hydroxyproline; Lipid Metabolism; Liver Cirrhosis; Oxidative Stress; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; Reactive Oxygen Species; Tea; Vitamin E

Generalized essential telangiectasia, which is a rare condition that is characterized by the progressive development of telangiectases on the skin, is a clinical diagnosis of exclusion. We present a 65-year-old man with a ten-month history of an asymptomatic eruption of the trunk and proximal aspects of the arms and hands that was comprised of macules and patches of telangiectases. The clinical presentation, associated diseases, hypotheses regarding pathogenesis, differential diagnoses, and reports on treatment modalities are reviewed. The relatively new association of this entity with systemic signs that include hemorrhage as well as the occurrence of generalized essential telangiectasia in patients with a history of hepatitis is discussed.

Topics: Aged; Alanine Transaminase; Ascorbic Acid; Aspartate Aminotransferases; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Platelet Count; Telangiectasis; Ultrasonography

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

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Dehydroascorbic Acid; Disease Models, Animal; Glucose Transporter Type 1; Humans; Intracellular Signaling Peptides and Proteins; Liver Cirrhosis; Mice; Mice, Knockout; PPAR gamma

Senescence marker protein 30 (SMP30), an important aging marker molecule that is highly expressed in the liver, has been known to protect hepatocytes from apoptosis by the synthesis of vitamin C. To explore the function of SMP30 in liver fibrosis, the effect of SMP30 deficiency on liver fibrosis was investigated in SMP30 knockout (KO) mice. Moreover, the in vivo results were further confirmed by way of hepatic stellate cell (HSC) isolation. We demonstrated that carbon tetrachloride (CCl(4))-induced liver fibrosis and the nuclear translocation of p-Smad2/3, the immediate downstream of transforming growth factor beta (TGF-beta), were significantly inhibited in the liver of SMP30 KO mice compared with wildtype (WT) mice. We also confirmed that both WT and SMP30 KO HSCs did not express SMP30. Finally, we further confirmed that up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) caused by a lack of vitamin C was the pivotal factor in the mechanisms for attenuated liver fibrosis of SMP30 KO mice, and feeding with vitamin C restored CCl(4)-induced liver fibrosis in SMP30 KO mice.. Vitamin C deficiency by SMP30 depletion attenuated liver fibrosis by way of up-regulated PPAR-gamma expression in SMP30 KO mice. Our results provide, for the first time, the possible mechanisms underlying inhibition of HSC activation associated with vitamin C and PPAR-gamma up-regulation in liver fibrosis of SMP30 KO mice.

Topics: Animals; Ascorbic Acid; Calcium-Binding Proteins; Carbon Tetrachloride Poisoning; Hepatic Stellate Cells; Intracellular Signaling Peptides and Proteins; Liver Cirrhosis; Male; Mice; Mice, Knockout; PPAR gamma; Smad Proteins

To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats.. Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method.. Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mug collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05).. Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Topics: Animals; Antioxidants; Ascorbic Acid; Cholestasis; Collagen; Drug Synergism; Female; Hyaluronic Acid; Ligation; Liver Cirrhosis; Liver Cirrhosis, Biliary; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Vitamin E

This study addressed the suggested association between levels of the antioxidants glutathione (GSH), vitamin C and vitamin E in peripheral blood and the histological activity and fibrosis stage in chronic hepatitis C (CHC). We then determined whether regular antioxidant supplementation influenced these antioxidant levels or disease severity.. Clinical, biochemical, histological and demographic data were collected from 247 CHC patients at the time of liver biopsy. Whole blood total GSH, plasma vitamin C and E were assessed by high-performance liquid chromatography. Statistical analyses were performed to test for associations between the variables and to identify independent predictors for hepatic necroinflammatory and fibrosis scores.. GSH and vitamin C, but not vitamin E correlated with both portal/periportal activity (r = -0.19, P = 0.004; r = -0.19, P = 0.009 respectively) and fibrosis stage (r = -0.18, P = 0.007; r = -0.18, P = 0.009 respectively). GSH was an independent negative predictor of portal/periportal inflammation (P = 0.02) and fibrosis (P = 0.01). Vitamin C was an independent negative predictor of fibrosis stage (P = 0.02). Antioxidant intake was associated with higher vitamin C (P < 0.0001) and vitamin E (P = 0.005) levels, but not GSH.. Whole blood GSH and plasma vitamin C are negatively associated with hepatic portal/periportal inflammation and fibrosis stage in CHC. Controlled intervention studies with vitamin C and agents that boost endogenous GSH levels are warranted.

Topics: Adolescent; Adult; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Biopsy; Cohort Studies; Dietary Supplements; Female; Glutathione; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Severity of Illness Index; Viral Load; Vitamin E

The chronome (from chronos, time, and nomos, rule; time structure) of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of preventive and curative chronotherapy.. Thirty patients with liver cirrhosis, 25-45 years of age, and 60 age-matched clinically healthy volunteers were synchronized for 1 week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical system were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, and serum total protein, albumin, ascorbic acid, and uric acid concentrations.. A marked circadian variation was demonstrated for each variable in each group by population-mean cosinor (P < 0.01). In addition to anticipated differences in overall mean value (MESOR), patients differed from healthy volunteers also in terms of their circadian pattern.. Mapping the broader time structure (chronome) with age and multifrequency rhythm characteristics of antioxidants and pro-oxidants is needed for exploring their putative role as markers in the treatment and management of liver cirrhosis.

Topics: Adult; Aging; Antioxidants; Ascorbic Acid; Biomarkers; Catalase; Chronobiology Phenomena; Female; Glutathione Peroxidase; Glutathione Reductase; Humans; Lipid Peroxides; Liver Cirrhosis; Male; Malondialdehyde; Middle Aged; Superoxide Dismutase

Oxidative stress, in particular lipid peroxidation, induces collagen synthesis. Thus, we administered various antioxidants to bile duct-ligated rats for 28 days and lipid peroxidation, glutathione content, fibrosis, necrosis and cholestasis were evaluated. Extrahepatic cholestasis was induced by double ligation and section of the common bile duct. The study included eight groups (n=6), four groups were bile duct-ligated and received either vitamin C (50 mg/kg/day, orally), vitamin E (400 IU/rat/day, orally), silymarin (50 mg/kg/12 hr, orally) or vehicles; four groups were sham-operated controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde was used to estimate lipid peroxidation levels; reduced and oxidized glutathione were determined fluorometrically; alanine aminotransferase and bilirubins colorimetrically. Bilirubins increased several times, alanine aminotransferase once, reduced/oxidized glutathione ratio decreased three times, lipid peroxidation and collagen increased about three-times by biliary obstruction (p<0.05). Silymarin, vitamin E or C failed to prevent these effects significantly. It is not possible to clarify the role of oxidative stress in the fibrotic process induced by chronic biliary obstruction with the present results. Therefore, it seems reasonable to propose that a wide mixture of antioxidants, administered by the parenteral route (because cholestasis decreased the absorption of lipophilic compounds), is needed to counteract the oxidant stress produced by cholestasis.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Cholestasis, Intrahepatic; Collagen; Glutathione; Lipid Peroxidation; Liver Cirrhosis; Male; Oxidative Stress; Rats; Rats, Wistar; Silymarin; Vitamin E

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Biopsy, Needle; Dietary Supplements; Fatty Liver; Female; Humans; Liver Cirrhosis; Male; Probability; Randomized Controlled Trials as Topic; Reference Values; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamin E

Nitric oxide (NO) modifies the functions of a variety of proteins containing cysteine thiols or transition-metal centers, particularly by S-nitrosylation. In inflamed liver, NO is overproduced and hepatic drug-metabolizing enzymes, the flavin-containing monooxygenases (FMOs) and cytochrome P450s (CYPs), are suppressed. However, the NO-related mechanisms underlying the loss of these activities are not well understood, particularly for FMOs. In this study, we suggest that FMO3, the major FMO in human liver, is modified post-translationally by NO. This hypothesis is based on the imbalance observed between the decrease in FMO3 expression (40.7% of controls) and FMO3-specific ranitidine N-oxidation activity (15.1%), and on the partial or complete reversibility of FMO inhibition by sulfhydryl-reducing regents such as DTT (effective on both S-S and S-NO adducts) and ascorbate (effective on S-NO only). Furthermore, NO donors (SNP, SNAP, and Sin-1), including the pure NO donor DEA/NO, directly suppressed in vitro FMO activity (N- or S-oxidation of ranitidine, trimethylamine, and thiobenzamide) in human liver microsomal proteins and recombinant human FMO3. These activities were restored completely after treatment with DTT or ascorbate. These results suggest that NO-mediated S-nitrosylation is involved in the rigorous inhibition of FMO activity in vitro and in vivo, resulting in the suppression of FMO-based drug metabolism or detoxification.

Topics: Adult; Ascorbic Acid; Carcinoma, Hepatocellular; Dithiothreitol; Enzyme Inhibitors; Hepatitis B, Chronic; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Methylamines; Microsomes, Liver; Middle Aged; Nitric Oxide; Nitric Oxide Donors; Nitrosation; Oxygenases; Ranitidine; Recombinant Proteins; Thioamides

This descriptive cross-sectional study aimed to investigate whether malnutrition occurs in outpatients with liver cirrhosis, and to compare the nutritional status of patients with alcoholic and viral liver cirrhosis using a variety of objective measures. This study also aimed to provide useful information about nutritional education and nutritional therapies for medical teams and patients with liver cirrhosis. Sixty-six Korean men between the ages of 30 and 69 with liver cirrhosis (24 alcohol-related and 42 virus-related) were recruited from the Internal Medicine Centres, Hanyang University Hospital, Seoul, Korea. The results showed that patients with alcoholic liver cirrhosis (ALC) were significantly lower in socio-economic status than patients with viral liver cirrhosis (VLC) (P<0.05). The energy intakes (excluding alcohol-derived energy) were 1448kcal and 1769kcal in the ALC and the VLC groups, respectively (P<0.05). As well, vitamin C intake was found to be higher in the VLC group than the ALC group, yet still more than 125% of the RDA for both groups (P<0.05). Among nutritional indices, only the TSF thickness showed interaction with the aetiology and the severity of the cirrhosis (P<0.05). Thus, these findings indicate that outpatients with liver cirrhosis in this study, particularly those with alcoholic liver cirrhosis, consumed a lower energy intake than suggested, but may not have been in a status of malnutrition. Body fat is more affected than other nutritional parameters in patients with liver cirrhosis.

Topics: Adult; Aged; Anthropometry; Ascorbic Acid; Body Composition; Cross-Sectional Studies; Hepatitis, Viral, Human; Humans; Korea; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Nutrition Assessment; Nutrition Disorders; Nutritional Status; Severity of Illness Index

The effects of glucan and liposomized glucan, alone or co-administered with vitamin C, and empty liposomes on hepatic fibrosis in mice infected with Mesocestoides corti (M. vogae) tetrathyridia were studied. Preparations were administered every third day from day 7 to day 31 post-infection (p.i.), nine doses in total. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cholesterol levels were measured in sera collected on days 11, 15, 21, 28, 32, 42, 50 and 65 p.i. Liver fibrosis was studied on the same days by measuring hydroxyproline concentration, which is considered a marker for collagen content. Larvicidal effects of the glucan and liposome preparations were estimated on day 65 p.i. in the liver and peritoneal cavity. Glucan formulations significantly enhanced collagen content, most prominently after administration of liposomized glucan in combination with vitamin C. Activities of both enzymes and cholesterol levels were slightly modified after administration of glucan alone. Liposomized glucan with vitamin C significantly increased ALT and AST activity and cholesterol levels up to days 28-32 p.i., after which they plateaued or declined. The most pronounced decrease was after administration of liposomized glucan and vitamin C. The same pattern of biochemical parameters in serum was observed after administration of empty liposomes, however, collagen content was not modified significantly. Larval counts in the liver and the peritoneal cavity were significantly reduced after treatment with either glucan formulation, but were unaffected following treatment with empty liposomes. In summary, intense fibrosis in the liver of mice treated with liposomized glucan and vitamin C did not result in the most extensive parenchymal cell injury but, rather in the highest efficacy of treatment. Liposomal lipids were probably utilized in the reparation of the damaged parenchymal cells, while glucan stimulated phagocytic cells.

Topics: Alanine Transaminase; Animals; Anticestodal Agents; Ascorbic Acid; Aspartate Aminotransferases; beta-Glucans; Cestode Infections; Collagen; Drug Carriers; Drug Therapy, Combination; Glucans; Liposomes; Liver; Liver Cirrhosis; Male; Mesocestoides; Mice; Mice, Inbred ICR; Peritoneal Cavity

To investigate the plasma levels of ascorbic acid and vitamin E in patients with liver cirrhosis and to explore their significance.. The plasma levels of ascorbic acid,vitamin E and lipoperoxides in patients with liver cirrhosis were measured, and the results were compared with those of sex-and age-matched healthy subjects.. The plasma levels of ascorbic acid, vitamin E and lipoperoxides in the patients group were (42.94 +/-6.99)micromol/L, (17.99 +/-3.51)micromol/L and (14.09 +/-1.28)micromol/L, respectively, while those in the control group were (53.30 +/-9.45)micromol/L (t=9.50, P=0.000), (24.59 +/-7.22)micromol/L (t=7.94, P=0.000) and (12.11 +/-1.20)micromol/L (t=17.21, P=0.000), respectively.. The levels of ascorbic acid and vitamin E in patients with liver cirrhosis decrease significantly,which may indicates the disturbance of balance between oxidation and antioxidation.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Female; Humans; Lipid Peroxides; Liver Cirrhosis; Male; Middle Aged; Vitamin E

Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats.. Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage.. Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05).. Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.

Topics: Animals; Antioxidants; Ascites; Ascorbic Acid; Bacterial Translocation; Combined Modality Therapy; Disease Models, Animal; Endotoxemia; Glutamic Acid; Intestinal Mucosa; Lactobacillus; Liver Cirrhosis; Male; Malondialdehyde; Oxidative Stress; Peritonitis; Probiotics; Rats; Rats, Sprague-Dawley

Chronic hepatitis C infection is a major world-wide problem, frequently progressing to cirrhosis, liver failure or hepatoma. The pathological mechanisms of disease progression are unclear but oxidant stress may play a role.. Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood or urine from 42 chronic hepatitis C patients. Fibrosis was graded histologically in a subgroup of 33 patients.. The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to reduced glutathione were significantly elevated (P<0.001, P=0.006). The antioxidants glutathione, selenium and vitamins A, C and E were significantly decreased (all P<0.001) compared to age and sex matched controls. Abnormal values were more marked in cirrhotics, but significant changes were also observed in the non-cirrhotic group. The fibrosis score correlated positively with urinary 8-isoprostane and type III procollagen peptide and negatively with vitamin A.. Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of hepatitis C infection. Although more severe in the cirrhotic group, there was clear evidence of oxidant stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role in slowing disease progression to cirrhosis.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Dinoprost; F2-Isoprostanes; Female; Glutathione; Hepatitis C, Chronic; Humans; Lipid Peroxidation; Liver Cirrhosis; Male; Middle Aged; Oxidative Stress; Selenium; Vitamin A; Vitamin E

The Na(+)/H(+) exchanger is the main intracellular pH (pH(i)) regulator in hepatic stellate cells (HSCs) and plays a key role in regulating proliferation and gene expression. We evaluated the effect of specific inhibition of this exchanger on HSC proliferation and collagen synthesis in vivo and in vitro.. Rat HSCs were incubated in the presence of platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, iron ascorbate (FeAsc), and ferric nitrilotriacetate solution (FeNTA) with or without the Na(+)/H(+) exchanger inhibitor 5-N-ethyl-N-isopropyl-amiloride (EIPA). pH(i) and Na(+)/H(+) exchanger activity, cell proliferation, and type I collagen accumulation were measured by using the fluorescent dye 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein, by immunohistochemistry for bromodeoxyuridine, and by enzyme-linked immunosorbent assay, respectively. In vivo liver fibrosis was induced by dimethylnitrosamine administration and bile duct ligation (BDL) in rats treated or not treated with amiloride.. PDGF, FeAsc, and FeNTA increased Na(+)/H(+) exchange activity and induced HSC proliferation. TGF-beta1 had no effect on the Na(+)/H(+) exchanger and was able, as for FeAsc and FeNTA, to induce type I collagen accumulation. EIPA inhibited all the effects determined by PDGF, FeAsc, and FeNTA and had no effect on TGF-beta1-induced collagen accumulation. In vivo, amiloride reduced HSC proliferation, activation, collagen deposition, and collagen synthesis.. The Na(+)/H(+) exchanger can play a key role in the development of liver fibrosis and in HSC activation in vivo.

Topics: Amiloride; Animals; Anti-Arrhythmia Agents; Antineoplastic Agents; Ascorbic Acid; Carcinogens; Cell Division; Collagen; Diuretics; Ferric Compounds; Ferrous Compounds; Gene Expression; Hydrogen-Ion Concentration; In Situ Nick-End Labeling; Liver; Liver Cirrhosis; Male; Nitrilotriacetic Acid; Procollagen; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA, Messenger; Sodium-Hydrogen Exchangers; Thymidine Phosphorylase; Transforming Growth Factor beta

Reactive oxygen species (ROS) induce HSCs activation, proliferation and collagen gene expression in vitro. Nitric oxide (NO) represents a reactive molecule that reacts with ROS, yielding peroxynitrite. We thus verified the effect of NO on ROS-induced HSCs proliferation in vitro and correlated iNOS expression and ROS formation to HSCs activation in the early phase of liver injury leading to hepatic fibrosis in vivo.. HSCs were incubated with iron ascorbate (FeAsc) in vitro, which induced ROS production, ERK1/2 phosphorylation and increased cell proliferation. This effect was significantly reduced by the presence of the NO donor S-nitroso-N-acetylpenicillamine. Liver injury was induced in vivo in rats by dimethylnitrosamine administration. HSCs activation started 6 h after DMN administration and peaked at 1 week. ROS generation and neutrophil infiltration were evident for at least 48 h after DMN treatment, showing an identical distribution pattern. Only a few inflammatory cells expressed iNOS 6 h after DMN administration.. we have shown that NO acts as a ROS scavenger in vitro, thus inhibiting HSCs proliferation. ROS production by infiltrating neutrophils occurs in the early phase of liver fibrosis and can represent a stimulus to HSCs activation in vivo. The reduced iNOS expression may account for the low NO levels and the inability to prevent the ROS-induced HSC activation in vivo.

Topics: Animals; Ascorbic Acid; Cell Division; Cells, Cultured; Dimethylnitrosamine; Disease Models, Animal; Drug Interactions; Free Radicals; Immunohistochemistry; Liver; Liver Cirrhosis; Male; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Penicillamine; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; S-Nitroso-N-Acetylpenicillamine

To assess the degree of oxidative stress, we measured plasma ubiquinone-10 percentage (%CoQ-10) in total amounts of ubiquinone-10 in patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma, and in age-matched control subjects, %CoQ-10 values were 12.9 +/- 10.3 (n = 28), 10.6 +/- 6.8 (n = 28), 18.9 +/- 11.1 (n = 20), and 6.4 +/- 3.3 (n = 16), respectively, showing a significant increase in oxidative stress in patient groups as compared to control subjects. There were no differences in total amounts of ubiquinone-10 and ubiquinol-10 among the four groups. We next measured %CoQ-10 in plasmas obtained from nine patients treated with percutaneous transluminal coronary angioplasty (PTCA). Plasmas were collected when hospitalized, and at the time (0, 4, 8, 12, 16, and 20 hr, and 1, 2, 3, 4, and 7 days) after the PTCA. %CoQ-10 values before and right after PTCA were 9.9 +/- 2.8 and 11.4 +/- 2.0, respectively, reached a maximum (20-45) at 1 or 2 days later, and decreased to 7.9 +/- 2.7 at 7 days after PTCA, indicating an increase in oxidative stress in patients during coronary reperfusion.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Ascorbic Acid; beta Carotene; Bilirubin; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Reference Values; Ubiquinone; Uric Acid; Vitamin E

We have applied our method for the simultaneous detection of plasma ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto, Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in these patients. The average ubiquinone-10 percentages (+/- S.D.) in total ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/- 10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant increase in ubiquinone-10 percentage in patient groups in comparison to normal subjects. These results and a significant decrease in the plasma ascorbate level in patient groups indicate that oxidative stress is evident after the onset of hepatitis and the subsequent cirrhosis and liver cancer.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Cholesterol; Cholesterol Esters; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Ubiquinone; Vitamin E

Results of examination and treatment of 157 patients with cholelithiasis against the background of a liver pathology were summed up. The antioxidant system in such patients was studied. The degree of a decrease of catalase activity in the liver and blood serum as well as the ascorbic acid content were found to depend on the liver state of patients with cholelithiasis. Greatest changes were found in patients with cirrhosis of the liver and chronic active hepatitis. The method of complex treatment of cholelithiasis patients with non-enzymatic antioxidants alpha-tocopherol and ascorbic acid is proposed. Activity of organ specific liver enzymes urokaninase and histidase was used for the estimation of treatment efficiency. Complex administration of ascorbic acid and alpha-tocopherol was shown to improve the liver function in patients operated upon for cholelithiasis.

Topics: Antioxidants; Ascorbic Acid; Bile; Biopsy; Catalase; Cholelithiasis; Combined Modality Therapy; Hepatitis, Chronic; Histidine Ammonia-Lyase; Humans; Liver; Liver Cirrhosis; Urocanate Hydratase

Four factors which stimulate collagen synthesis and prolyl hydroxylase activity in cultures of human and mouse fibroblasts have been isolated by molecular sieve chromatography from animal and human fibrotic and cirrhotic livers. These factors do not stimulate protein or DNA synthesis or total DNA in these cultures. It has also been shown that these factors, designated collagen stimulating factors F1-F4, do not owe their activity to ascorbate or glutamine. Collagen stimulating factors are heat stable, and F1 and F2 have apparent molecular weights of about 4000 and 1000 respectively. Since these factors are not present in normal animal or human liver it is suggested that they may be responsible for increased collagen production in vivo in hepatic fibrosis and cirrhosis.

Topics: Animals; Ascorbic Acid; Cell Line; Chromatography, Gel; Collagen; DNA; Fibroblasts; Glutamine; Humans; Liver; Liver Cirrhosis; Male; Mice; Procollagen-Proline Dioxygenase; Protein Biosynthesis; Tissue Extracts

Adult patients with transfusional hemosiderosis were given ascorbic acid and treated with the iron chelator, desferrioxamine B. The drug was administered by continuous subcutaneous or intravenous infusions using a light weight portable constant infusion device. On this regimen, four of the five patients studied were able to excrete significant amounts of iron (greater than 35 mg/da) when receiving a daily desferrioxamine dose of 1.5 to 2.2 g. Continuous subcutaneous infusion was well tolerated and about 80 per cent as effective as intravenous therapy in chelating iron. The number of prior transfusions, the hepatic iron content and the serum ferritin levels appear to be useful in predicting which patients will respond to iron chelation therapy, especially if there is little bone marrow erythropoietic activity. One patient with ineffective erythropoiesis did not have significantly increased hepatic iron stores but responded to the administration of desferrioxamine. Continuous subcutaneously administered desferrioxamine may prove to be adaptable for long-term outpatient therapy, allowing patients with ongoing transfusion requirements to go into negative iron balance. Long-term studies will be needed to demonstrate reversal of endocrine, hepatic and cardiac dysfunction secondary to iron deposition in these patients.

Topics: Adult; Aged; Ascorbic Acid; Biopsy, Needle; Deferoxamine; Female; Ferritins; Hemosiderosis; Humans; Infusions, Parenteral; Iron; Liver; Liver Cirrhosis; Male; Middle Aged; Primary Myelofibrosis; Transfusion Reaction

Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). In the primary biliary cirrhosis patients, cholestyramine therapy was associated with significantly lower levels of the vitamin (P less than 0-05). Liver ascorbic acid measured in Menghini needle biopsies in 20 patients was significantly correlated with LAA (r=0-807, P less than 0-001). No significant correlation was found between LAA and haematological indices, conventional liver function tests, or cholesterol levels in any group of patients. Patients with LAA levels below 100 nM/10(8) WBC had significantly higher antipyrine half-lives (mean=28-3 h) than patients with LAA levels above this level (mean=18-6 h) (P less than 0-05). Delayed drug metabolism related to low LAA should be considered when drugs metabolised by the liver are prescribed for patients with alcoholic liver disease or primary biliary cirrhosis.

Topics: Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Cholestyramine Resin; Humans; Leukocytes; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Function Tests

Topics: Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Humans; Liver Cirrhosis; Pyridoxal Phosphate; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Topics: Ascorbic Acid; Chronic Disease; Hepatitis; Humans; Liver Cirrhosis; Vitamin E

Topics: Ascorbic Acid; Blood; Carbon Radioisotopes; Enzyme Activation; Erythrocytes; Flavin-Adenine Dinucleotide; Flavins; Glucosephosphate Dehydrogenase Deficiency; Glutathione Reductase; Hemolysis; Humans; Liver Cirrhosis; Methylene Blue; Riboflavin; Umbilical Cord; Uremia

Topics: Ascorbic Acid; Child, Preschool; Diet; Female; Humans; Infant; Liver Cirrhosis; Male

Topics: Anabolic Agents; Animals; Ascorbic Acid; Body Weight; Carbon Tetrachloride Poisoning; Drug Synergism; Female; Guinea Pigs; Injections, Subcutaneous; Liver Cirrhosis; Male; Nicotinic Acids; Organ Size; Prednisone; Sex Factors; Vitamin B 12

Topics: Acute Disease; Ascorbic Acid; Bilirubin; Cholestasis; Cholesterol; Chronic Disease; Coenzymes; Exchange Transfusion, Whole Blood; gamma-Globulins; Glucocorticoids; Hepatitis A; Humans; Hyperbaric Oxygenation; Liver Cirrhosis; Liver Function Tests; Oxygen Inhalation Therapy; Sulfobromophthalein; Transaminases; Vitamin B Complex

Topics: Animals; Ascorbic Acid; Cobalt; Copper; Cysteine; Dactinomycin; Deferoxamine; Dinitrophenols; Edetic Acid; Fatty Liver; Fluorides; Fructose; Glucose; Glutathione; Hemochromatosis; Inflammation; Iodoacetates; Iron; Lipotropic Agents; Liver Cirrhosis; Lung; Macrophages; Microscopy, Electron; Potassium Permanganate; Protein Biosynthesis; Puromycin; Rabbits; RNA; Saponins; Sucrose; Surface-Active Agents; Transferrin; Trypsin

Topics: Antifibrinolytic Agents; Ascorbic Acid; Blood Coagulation Disorders; Hemostatics; Humans; Liver Cirrhosis; Vitamin K

Topics: Ascorbic Acid; Humans; Intestinal Absorption; Intestinal Mucosa; Iron; Liver Cirrhosis

Topics: Ascorbic Acid; Colitis, Ulcerative; Duodenal Ulcer; Gastrointestinal Diseases; Hernia, Diaphragmatic; Humans; Leukocytes; Liver Cirrhosis

Topics: Adult; Aged; Animals; Ascorbic Acid; Diagnosis, Differential; Female; Haptoglobins; Hepatitis; Humans; Liver; Liver Cirrhosis; Liver Function Tests; Male; Methionine; Middle Aged; Rabbits; Rats; Vitamin K

Topics: Ammonia; Ascorbic Acid; Glutamates; Glutamine; Humans; Ketoglutaric Acids; Liver Cirrhosis

Topics: Ascorbic Acid; Female; Fructose; Humans; Liver Cirrhosis; Male; Pancreatic Extracts; Portacaval Shunt, Surgical; Postoperative Care; Potassium; Suture Techniques; Thioctic Acid; Vitamin B Complex

Topics: Ammonia; Ascorbic Acid; Humans; Liver Cirrhosis

Topics: Ammonia; Ascorbic Acid; Glutathione; Humans; Liver Cirrhosis; NAD

Topics: Animals; Ascorbic Acid; Liver Cirrhosis; Metabolism; Rabbits; Research

Topics: Animals; Ascorbic Acid; Blood; Blood Bactericidal Activity; Complement Fixation Tests; Guinea Pigs; Humans; Immunity; Immunity, Active; In Vitro Techniques; Liver Cirrhosis; Phagocytosis

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Digestion; Gastroenterology; Humans; Liver Cirrhosis; Vitamins

Topics: Achlorhydria; Ascorbic Acid; Blood Chemical Analysis; Humans; Hydrochloric Acid; Intestinal Absorption; Intestine, Small; Intestines; Liver Cirrhosis; Metabolism; Vitamins

Topics: Ascorbic Acid; Blood Chemical Analysis; Deficiency Diseases; Diuretics; Edema; Intestine, Small; Intestines; Liver Cirrhosis; Mineralocorticoid Receptor Antagonists; Prednisone; Spironolactone

Topics: Amino Acids; Ascorbic Acid; Honey; Humans; Liver Cirrhosis; Vitamin B Complex; Vitamins

Topics: Ascorbic Acid; Humans; Leukemia; Leukemia, Myeloid; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Polycythemia Vera; Vitamin A; Vitamins

Topics: Animals; Ascorbic Acid; Dairy Products; Humans; Liver Cirrhosis; Milk; Powders; Vitamins