title: Protection of nicotinic acid against oxidative stress-induced cell death in hepatocytes contributes to its beneficial effect on alcohol-induced liver injury in mice.
abstract: Oxidative stress plays a pathological role in the development of alcoholic liver disease. In this study, we investigated the effects of nicotinic acid (NA) supplementation on H2O2-induced cell death in hepatocytes and alcohol-induced liver injury in mice. Hepatocytes were exposed to H2O2 (0-0.4 mM) for 16 h after a 2-h pretreatment with NA (0-100 μM). Cell viability, intracellular glutathione and total NAD contents were determined. In animal experiments, male C57BL/6 mice were exposed to Lieber-De Carli liquid diet [+/- ethanol with/without NA supplementation (0.5%, w/v) for 4 weeks]. Nicotinic acid phosphoribosyltransferase (NaPRT) is the first enzyme participated in the NA metabolism, converting NA to nicotinic acid mononucleotide (NaMN). In NaPRT-expressing Hep3B cells, H2O2-induced cell death was attenuated by NA, whereas in NaPRT-lost HepG2 cells, only NaMN conferred protective effect, suggesting that NA metabolism is required for its protective action against H2O2. In Hep3B cells, NA supplementation prevented H2O2-inudced declines in intracellular total NAD and GSH/GSSG ratios. Further mechanistic investigations revealed that conservation of Akt activity contributed to NA's protective effect against H2O2-inudced cell death. In alcohol-fed mice, NA supplementation attenuated liver injury induced by chronic alcohol exposure, which was associated with alleviated hepatic lipid peroxidation and increased liver GSH concentrations. In conclusion, our findings indicate that exogenous NA supplementation may be an ideal choice for the treatment of liver diseases that involve oxidative stress.
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P R China.
authors: Xiaobing
authors: X
authors: Dou
authors: Chen
authors: C
authors: Shen
authors: Zhigang
authors: Z
authors: Wang
authors: Songtao
authors: S
authors: Li
authors: Ximei
authors: X
authors: Zhang
authors: Zhenyuan
authors: Z
authors: Song
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009525:Niacin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D009525:Niacin; D006861:Hydrogen Peroxide; D005978:Glutathione
keywords: Alcohol; Glutathione; Hydrogen peroxide; Liver; Nicotinic acid; Oxidative stress