title: Endogenous A1 adenosine receptor protects mice from acute ethanol-induced hepatotoxicity.
abstract: Previous studies have indicated a critical role of adenosine and its receptors in the pathogenesis of liver diseases. The aim of this study was to determine the contribution of A1 adenosine receptor (A1AR) to acute ethanol-induced hepatotoxicity. Wild-type (WT) and A1AR(-/-) mice were intragastrically administered with ethanol (5 g/kg), and hepatic injury was evaluated 6h thereafter. Mice lacking A1AR were more susceptible to ethanol-induced liver damage than WT mice, as evidenced by higher serum transaminase levels and increased extent of histopathological changes. Ethanol induced triglycerides accumulation in the serum and liver, and this accumulation was augmented in A1AR(-/-) mice. Analysis of gene expression in the liver revealed up-regulated mRNA levels of genes related to lipogenesis (including: FAS, SCD1, ACC1, DGAT2, and PPARγ) in A1AR(-/-) mice after ethanol treatment. In addition, lack of A1AR aggravated lipid peroxidation and superoxide dismutase depletion caused by acute ethanol exposure. A subsequent study revealed that, pretreatment with A1AR antagonist DPCPX increases the sensitivity of mice to ethanol-induced liver injury. In conclusion, these results indicated that endogenous A1AR activation protects mice against acute ethanol-induced liver injury by reducing oxidative stress and decreasing lipid accumulation.
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China. yp_apple@yeah.net
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wang
authors.forename: Yibei
authors.initials: Y
authors.lastname: Zhan
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Mengyi
authors.initials: M
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Jianfa
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
chemical_list: D043682:Receptor, Adenosine A1; D000431:Ethanol