Impact of massive ascorbic acid supplementation on alcohol induced oxidative stress in guinea pigs.
ABSTRACT The effects of a mega dose of ascorbic acid (AA) on alcohol induced peroxidative damages were investigated in guinea pigs. In the present study, four groups of male guinea pigs were maintained for 30 days as follows. (1) Control group (1 mg AA/100 g body wt); (2) Ethanol group (1 mg AA/100 g body wt. + 9 g ethanol/kg body wt); (3) AA group (25 mg AA/100 g body wt); (4) AA + ethanol group (25 mg AA/100 g body wt. + 9 g ethanol/kg). Results revealed that alcohol induced significant lipid peroxidation, since the lipid peroxidation products malondialdehyde (MDA), hydroperoxides and conjugated dienes were elevated. The activities of scavenging enzymes superoxide dismutase (SOD), catalase were reduced. However, supplementation of AA along with alcohol reduced the lipid peroxidation products in the liver and enhanced the activities of scavenging enzymes. Activities of glutathione peroxidase and reductase were also greater in guinea pigs given alcohol + AA in comparison with those given alcohol alone. Administration of ascorbic acid also reduced the activity of gamma-glutamyl transpeptidase (GGT), the marker enzyme of alcohol induced toxicity. The vitamin E level, which was reduced by alcohol intake, was raised by the co-administration of AA and alcohol. These studies suggest that a mega dose of AA helps in the prevention of alcohol induced oxidative stress by enhancing the antioxidant capacity and also by reducing the lipid peroxidation products.
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ABSTRACT: Ethanol metabolism induces generation of excessive amount of reactive oxygen species (ROS) which results in immune dysfunction. We examined the efficacy of silymarin on ethanol-induced oxidative stress, immunomodulatory activity, and vascular function in mice blood. Effectiveness of silymarin was compared with potent antioxidant ascorbic acid. In the present study, 8- to 10-week-old male BALB/c mice (20-30 g) were divided into the four groups of six each. One group were fed with ethanol (1.6 g/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and silybin (250 mg/kg body weight), and the third group were exposed to ethanol (250 mg/kg body weight) and ascorbic acid (250 mg/kg body weight) per day for 12 weeks. The control group was fed with isocaloric glucose solution instead of ethanol. Ethanol exposure significantly increased thiobarbituric acid reactive substance (TBARS) and nitrite levels besides glutathione-S-transferase (GST) activity, and significantly decreased reduced glutathione (GSH) content and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in whole blood hemolyzate, while silymarin treatment significantly normalized these altered parameters. Silymarin significantly prevented ethanol-induced, elevated activities of interleukin (IL)-10, tumor necrosis factor (TNF)-α, γ interferon (IFN-γ), vascular endothelial growth factor (VEGF)-A, and transforming growth factor (TGF)-β1, as well as decreased IL-4 activity in mice blood. These results were comparable with the activity of ascorbic acid.Toxicology mechanisms and methods 03/2012; 22(5):409-13. · 1.37 Impact Factor
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ABSTRACT: 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-β1 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.Journal of physiology and biochemistry 05/2013; · 1.65 Impact Factor
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ABSTRACT: Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signalling 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 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.Toxicology and Applied Pharmacology 11/2013; · 3.98 Impact Factor