ascorbic-acid and Liver-Cirrhosis--Alcoholic

Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4g/kg b.wt for 90days. After 90days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250mg/kg b.wt) and AA (250mg/kg b.wt) supplemented groups and maintained for 30days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β1 and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α1 (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis.

Topics: Animals; Ascorbic Acid; Claudins; Endotoxemia; Endotoxins; Ethanol; Guinea Pigs; Hepatic Stellate Cells; I-kappa B Proteins; Interleukin-6; Intestines; Liver; Liver Cirrhosis, Alcoholic; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Occludin; RNA, Messenger; Signal Transduction; Silymarin; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Zonula Occludens-1 Protein

Both oxidative stress and inflammatory reactions play a major role in alcoholic liver fibrosis. We evaluated the efficacy of ascorbic acid (AA) and silymarin in the regression of alcohol-induced inflammation in hepatocytes of guinea pigs (Cavia porcellus). Animals were administered with ethanol at a daily dose of 4 g/kg body weight (b.wt) for 90 days. On the ninety-first day, ethanol administration was stopped and animals were divided into alcohol abstention group and silymarin- (25 mg/100 g b.wt) and AA- (25 mg/100 g b.wt) supplemented groups and maintained for 30 days. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in the serum of the ethanol group. The intracellular reactive oxygen species (ROS) and expressions of cytochrome P4502E1 and nuclear factor κB1, tumor necrosis factor-α, and transforming growth factor-β(1) in hepatocytes were significantly increased in ethanol group. The fibrotic markers α-smooth muscle actin and α(1)(I) collagen and activity of cytotoxicity marker caspase-3 were significantly increased and AA content was significantly reduced in hepatocytes of alcohol-treated guinea pigs. But the AA and silymarin supplementation significantly reduced these changes in comparison with alcohol abstention group. AA could induce greater reduction of inflammatory and fibrotic markers in hepatocytes than silymarin. This indicates that AA is superior to silymarin in inhibiting intracellular ROS generation and thereby reducing the ethanol-induced inflammation in hepatocytes.

Topics: Actins; Alanine Transaminase; Animals; Antioxidants; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; Aspartate Aminotransferases; Collagen Type I; Collagen Type I, alpha 1 Chain; Disease Models, Animal; Ethanol; gamma-Glutamyltransferase; Gene Expression; Guinea Pigs; Hepatocytes; Liver; Liver Cirrhosis, Alcoholic; Male; NF-kappa B; Oxidative Stress; Protective Agents; Reactive Oxygen Species; Silymarin; Steroid Hydroxylases; Transforming Growth Factor beta

Both oxidative stress and endotoxins mediated immunological reactions play a major role in the progression of alcoholic hepatic fibrosis. Ascorbic acid has been reported to reduce alcohol-induced toxicity and ascorbic acid levels are reduced in alcoholics. Hence, we investigated the hepatoprotective action of ascorbic acid in the reversal of alcohol-induced hepatic fibrosis in male guinea pigs (n = 36), and it was compared with the animals abstenting from alcohol treatment. In comparison with the alcohol abstention group, there was a reduction in the activities of toxicity markers and levels of lipid and protein peroxidation products, expression of α-SMA, caspase-3 activity and mRNA levels of CYP2E1, TGF-β(1), TNF-α and α(1)(I) collagen in liver of the ascorbic acid-supplemented group. The ascorbic acid content in liver was significantly reduced in the alcohol-treated guinea pigs. But it was reversed to normal level in the ascorbic acid-supplemented group. The anti-fibrotic action of ascorbic acid in the rapid regression of alcoholic liver fibrosis may be attributed to decrease in the oxidative stress, hepatic stellate cells activation, cytotoxicity and mRNA expression of fibrotic genes CYP2E1, TGF-β(1), TNF-α and α(1) (I) collagen in hepatic tissues.

Topics: Animals; Ascorbic Acid; Biomarkers; Caspase 3; Collagen Type I; Cytochrome P-450 CYP2E1; Down-Regulation; Free Radical Scavengers; Guinea Pigs; Hepatic Stellate Cells; Lipid Peroxidation; Liver; Liver Cirrhosis, Alcoholic; Male; Oxidative Stress; Protein Carbonylation; RNA, Messenger; Transcription, Genetic; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

The aim was to study the effect of naringenin, a biologically active compound, on tissue antioxidant status and lipid peroxidation in ethanol-induced hepatotoxicity in rats.. Rats were divided into four groups: Groups 1 and 2 received isocaloric glucose and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment.. The results showed significantly elevated levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione and vitamins C and E in ethanol-treated rats compared with control rats. Administration of naringenin to rats with ethanol-induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, gamma-glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol-treated rats. Histological changes observed in the liver correlated with the biochemical findings.. Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol-induced hepatotoxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Biological Products; Disease Models, Animal; Flavanones; Heart; Kidney; Lipid Peroxidation; Liver Cirrhosis, Alcoholic; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E

Hyperdynamic circulation and systemic vasodilation complicate cirrhosis of the liver and are related to vasoconstrictor hyporeactivity. We investigated whether impaired vasoconstrictor responsiveness may be overcome by antioxidants in patients with decompensated alcoholic cirrhosis.. Controlled clinical study.. University setting.. Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers.. Forearm blood flow responses to intra-arterial norepinephrine, angiotensin II, and the nitric oxide synthase inhibitor N-monomethyl-l-arginine were measured by strain-gauge plethysmography and compared between groups of patients. To assess the role of oxidative stress, the antioxidant vitamin C (24 mg/min) was administered locally into the brachial artery, and forearm blood flow responses were reassessed.. Plasma concentrations of vitamin C were lower in patients with cirrhosis (p < .05). In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects. No changes were observed in time-control experiments in cirrhosis patients (n = 3) employing vehicle coinfusion. The response to N-monomethyl-L-arginine was comparable between groups and not affected by vitamin C.. Oxidative stress with consumption of antioxidants seems to play an important role in the development of vasoconstrictor hyporeactivity in patients with cirrhosis. Antioxidant therapy may be a promising clinical approach to restore vasoconstrictor hyporeactivity in these patients.

Topics: Angiotensin II; Antioxidants; Ascites; Ascorbic Acid; Female; Forearm; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Norepinephrine; omega-N-Methylarginine; Oxidative Stress; Vasoconstriction; Vasoconstrictor Agents

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

We report on the prooxidant (lipid peroxides) and antioxidant levels (ascorbic acid, reduced glutathione, superoxide dismutate activity) in healthy individuals (30) and patients with cirrhosis (37; 22 alcoholic cirrhosis and 15 non alcoholic cirrhosis). A significant increase in plasma lipid peroxide (P < 0.05) and ascorbic acid (P < 0.01) and a significant decrease in reduced glutathione (P < 0.001) and superoxide dismutase activity (P < 0.05) in haemolysate was observed in cirrhosis patients compared to the control group. A significant decrease in reduced glutathione (P < 0.01) and superoxide dismutase (P < 0.05) activity was also observed when the alcoholic cirrhosis group was compared to non alcoholic group. A significant increase in aspartate transaminase (P < 0.05), gamma glutamyl transaminase (P < 0.01) and aspartate transaminase/alanine transaminase (P < 0.05) ratio was seen in alcoholic cirrhosis group. A significant positive correlation between gamma glutamyl transferase and lipid peroxides (r = 0.48, P < 0.05) was observed in alcoholic cirrhosis.

Topics: Alanine Transaminase; Ascorbic Acid; Aspartate Aminotransferases; Humans; Lipid Peroxides; Liver Cirrhosis, Alcoholic; Oxidative Stress

Rhesus monkeys that were maintained on a diet containing low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the total caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg(-1) d[-1]) over a period of 3 years. In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes. The amount of alcohol consumed correlated positively with plasma lipid peroxidation products, 4-hydroxynonenal (4-HNE) and 8-isoprostane F2alpha, and negatively with 20:4n6 and 22:6n3 levels. These findings imply that alcoholics who also have a marginal intake of essential fatty acids and antioxidants in their diets may be at an increased risk of developing liver disease.

Topics: Aldehydes; Animals; Antioxidants; Ascorbic Acid; Dietary Fats, Unsaturated; Dinoprost; Erythrocytes; Ethanol; F2-Isoprostanes; Fatty Acids; Fatty Acids, Unsaturated; Lipid Peroxidation; Lipoproteins, VLDL; Liver; Liver Cirrhosis, Alcoholic; Macaca mulatta; Male; Olive Oil; Plant Oils; Vitamin A

Topics: Alcoholism; Ascorbic Acid; Humans; Leukocytes; Liver Cirrhosis, Alcoholic; Liver Diseases

Biochemical evidence of thiamine deficiency was found in 58% of patients with chronic liver disease, the incidence being higher in alcoholic than in non-alcoholic patients. Daily supplementation with high doses of thiamine hydrochloride (200 mg/day) for one week restored levels of thiamine pyrophosphate (TPP), the active co-enzyme form of thiamine, to normal in all cases. Such supplementation also stimulated synthesis of the TPP dependent enzyme transketolase. Because of the essential role of TPP as a co-factor in intermediary metabolism, it is concluded that high doses of thiamine should be included in the routine nutritional management of patients with severe chronic liver disease.

Topics: Ascorbic Acid; Chronic Disease; Erythrocytes; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases; Pyridoxine; Thiamine; Thiamine Deficiency; Transketolase

Vitamin C status was studied, by means of leucocyte ascorbic acid concentrations, in 67 cases of idiopathic hemochromatosis subdivided into 44 untreated and 25 treated cases (2 patients belonging to both subgroups) and compared to 31 normal subjects and 37 alcoholic cirrhosis patients. The control groups exhibited the following mean levels (+/- SEM): 34.4 +/- 1.9 microgram/10(8) WBC in normals and 22.0 +/- 1.8 microgram/10(8) WBC in alcoholic cirrhosis. In idiopathic hemochromatosis the mean levels were: for the untreated group 19.5 +/- 1.7 microgram/10(8) WBC and for the treated group 34.3 +/- 2.3 microgram/10(8) WBC. These results (1) affirm an important vitamin C deficiency in the untreated disease; (2) suggest that iron overload is the main causal factor in view of the striking difference--to date unreported--between untreated and treated cases of idiopathic hemochromatosis. Besides its possible theoretical interests, this vitamin C deficiency is responsible in idiopathic hemochromatosis for a significant underestimation of the desferrioxamine-induced urinary iron excretion.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Hemochromatosis; Humans; Iron; Leukocytes; Liver Cirrhosis, Alcoholic; Liver Function Tests; Male; Middle Aged

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