Pharmacological blockage of CYP2E1 and alcohol-mediated liver cancer: is the time ready?

Chronic alcohol consumption is a major risk factor worldwide affecting significantly both mortality and years of life lost （YLL） （1）. Ca. 5% of the western world show risky alcohol consumption and in some countries such as China a regional yearly increase of alcohol consumption of over 400% has been observed recently （2,3）. The liver is the major target organ of alcohol. According to the recently published ＇Global Burden of Disease Study 2010, liver cirrhosis and liver cancer are ranked at position 12 and 16 in the global deaths statistics （1）. Thus, in 2010, ca. 1 million people died from liver cirrhosis with one third directly attributable to alcohol. This is a considerable number when comparing with coronary heart disease with 7 million deaths and the leading cause of mortality. In central Europe, liver cirrhosis even ranks at the fourth position in YLL. Hepatocellular cancer （HCC） is now the most common fatal complication of patients with alcoholic cirrhosis. Moreover, it shows the second fastest increase of all tumors worldwide after kidney tumors and alcohol-associated HCC ranks on third position after HCCs caused by viral hepatitis B and C.

The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats

Objective:This study was performed to investigate the protective effect of Thymus vulgaris(T.vulgaris) leaves 70%alcoholic extract against alcohol-mediate hepatotoxicity rats.Methods:The protective effect of extract was investigated at dose of 500 mg/kg/day orally against alcohol-mediate hepatotoxicity using adult male Wister albino rats during 21 days.Protective effect of T.vulgaris extract was evaluated comparing with silymarin standard drug al recommended dose(25 mg/kg/day) orally for 21 days.Results:Alcohol-mediate hepatotoxicity rats(alcohol-control) showed hepatocytes distortion represented as marked increment on liver biomarkers;alkaline phosphatase(ALP),aspartate transaminase(AST) and alanine transaminase(ALT) activities,as well as pronounced reduction on total protein and its fractions albumin and globulin corresponding to normal ranges.Addition to oxidative stress status as depletion on glutathione concentration,catalase(CAT),superoxide dismutase(SOD),glutathione reductase(GR),glutathione-S-transferase(GST) and glutathione peroxidase(GPx)activities,concurrence with augmentation oxidative stress parameters;malondyaldchydc(MDA) and hydrogen peroxide(H_2O_2) concentrations comparing to normal values.Alcohol administration elevated total cholesterol(TC),low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol(HDL-C) comparing to normal ranges.Co-administration T.vulgaris extract with alcohol showed protective effect on hepatocytes manifested as minimizing on ALP.AST and ALT activities and increment on total protein,albumin and globulin production compared to alcohol-control.Antioxidant enzymes activities;CAT.SOD.GR,GST and GPx were significantly magnified,while MDA and H_2O_2 concentration were lessened corresponding to alcohol-control.Also,lipid profile was markedly improved and risk ratio was lowered compared to alcohol-control.These results were confirmed by normalization of degenerated and fibrotic liver tissue as of alcohol-control.Conclusion:T.vulgaris extract appeared hepatoprotective,hypolipidemic and antioxidant activities on alcohol-mediate hepatotoxicity rats compared to silymarin.