Silymarin protects against paracetamol-induced lipid peroxidation and liver damage.
ABSTRACT The effect of silymarin on liver damage induced by acetaminophen (APAP) intoxication was studied. Wistar male rats pretreated (72 h) with 3-methylcholanthrene (3-MC) (20 mg kg-1 body wt. i.p.) were divided into three groups: animals in group 1 were treated with acetaminophen (APAP) (500 mg kg-1 body wt. p.o.), group 2 consisted of animals that received APAP plus silymarin (200 mg kg-1 body wt. p.o.) 24 h before APAP, and rats in group 3 (control) received the equivalent amount of the vehicles. Animals were sacrificed at different times after APAP administration. Reduced glutathione (GSH), lipid peroxidation and glycogen were measured in liver and alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and glutamic pyruvic transaminase (GPT) activities were measured in serum. After APAP intoxication, GSH and glycogen decreased very fast (1 h) and remained low for 6 h. Lipid peroxidation increased three times over the control 4 and 6 h after APAP treatment. Enzyme activities increased 18 h after intoxication. In the group receiving APAP plus silymarin, levels of lipid peroxidation and serum enzyme activities remained within the control values at any time studied. The fall in GSH was not prevented by silymarin, but glycogen was restored at 18 h. It was concluded that silymarin can protect against APAP intoxication through its antioxidant properties, possibly acting as a free-radical scavenger.
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ABSTRACT: The accumulation of toxic hydrophobic bile acids into hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In the present work we have reported that changes observed in the expression of lipogenic enzymes, acetyl-CoA carboxylase and fatty acid synthase were associated to a decrease in the activity of citrate carrier (CIC), protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and antiiflammatory properties, prevented mitochondrial ROS production, cardiolipin oxidation and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusions, we demonstrated that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property.Free Radical Biology & Medicine 05/2014; · 5.27 Impact Factor
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ABSTRACT: Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation.Indian Journal of Pharmaceutical Sciences 11/2013; 75(6):642-8. · 0.34 Impact Factor
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ABSTRACT: BACKGROUND AND OBJECTIVE: Coffee plants can alter the activity of liver enzymes and reduce liver enzymes. Considering vital role of liver in the detoxification and the role of dietary factors in enhancing the body's ability to detoxify the chemicals and drugs, the present study was performed to determine the protective effect of boiled coffee on liver enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin in rats treated with thioacetamide. METHODS: In this experimental study, 32 male rats were divided into four groups of eight. Animals in the first group (control) received water and normal food for rats, group II (control) received water and normal food associated with the injection of 1 ml of normal saline as a solvent, and the third group received both normal food and water. For injecting thioacetamide (100 mg/kg) the treated group received no intervention and the fourth group received boiled coffee (4 mg/kg) orally in the diet of rats during 68 days (pretreatment). The average length of treatment time for pretreatment was considered from 8 to 10 weeks. Blood samples were taken at two stages: pretreatment and post injection of thioacetamide intraperitoneally at the dose of 100 mg/kg. AST, ALT, ALP and total bilirubin were measured 48 hours after last injection. FINDINGS: The results showed a significant increase of the rate of serum AST in treated group with thioacetamide (321±26) in compared to control group (162±3). Boiled coffee as pretreatment has protective effect on liver tissue. The rate of ALP in this group was 384±39 that significantly decreased (p<0.05). CONCLUSION: In this study, boiled coffee has protective effect on liver enzymes.BABOL UNIVERSITY OF MEDICAL SCIENCES. 07/2014; 16(7):41-49..