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Novel Protective Role of Nicotinamide Phosphoribosyltransferase in Acetaminophen-induced Acute Liver Injury in Mice

ABSTRACT: Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the USA. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild type (Nampt+/+)-, heterozygous knockout (Nampt+/-)-, and overexpression (NamptOE)-mice were treated with overdose of acetaminophen, followed by histological, biochemical, and transcriptomic evaluation of liver injury. The mechanism of Nampt in acetaminophen -induced hepatocytic toxicity was also explored in cultured primary hepatocytes. Three lines of evidence have convergently demonstrated that acetaminophen overdose triggers the most severe oxidative stress and necrosis, and the highest expression of key necrosis driving genes in Nampt+/- mice, while the effects in NamptOE mice were least severe relative to Nampt+/+ mice. These findings support that NAMPT protects against acetaminophen induced ALI.

ORGANISM(S): Mus musculus

PROVIDER: GSE110787 | GEO | 2018/04/03

REPOSITORIES: GEO

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