Effect of hyperleptinaemia on chronic ethanol-induced hepatotoxicity in mice.
Ethanol metabolism is accompanied by generation of free radicals, which stimulate lipid peroxidation. Previous studies have proposed a possible link between leptin and non-alcoholic fatty liver disease; however, the effect of leptin on ethanol-induced liver diseases remains unclear. The aim of the present study was to explore the effect of leptin on ethanol-induced liver injury in mice. Administering ethanol (6.32 g/kg body weight p.o.) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of plasma leptin, total bilirubin, gamma-glutamyl transpeptidase (GGT), tissue lipid hydroperoxides (LOOH), and lowered levels of tissue vitamins C and E when compared with those of the control mice. Subsequent to the experimental induction of hepatotoxicity (i.e. after the initial period of 30 days) exogenous leptin was administered (230 microg/kg body weight i.p.) every alternate day for 15 days along with the daily dose of ethanol. Leptin administration to control and ethanol-treated mice significantly reduced the weight gain, elevated the plasma levels of leptin, bilirubin, GGT and tissue LOOH, and significantly lowered the levels of tissue vitamins C and E when compared with the untreated control and ethanol-supplemented mice. It is postulated that the increase in systemic leptin levels enhances oxidative stress, and lowers antioxidant defence, leading to the augmented hepatic inflammation observed in alcoholic liver disease.
Balasubramaniyan
Vairappan
V
Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, Tamilnadu, India.
Nalini
Namasivayam
N
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D006519:Hepatitis, Alcoholic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020738:Leptin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D015227:Lipid Peroxidation; D008108:Liver Diseases, Alcoholic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice
D020738:Leptin; D000431:Ethanol