Nicotinamide improves NADlevels to protect against acetaminophen-induced acute liver injury in mice.
Hum Exp Toxicol. 2021 May 5:9603271211014573. Epub 2021 May 5. PMID: 33949241
Acetaminophen (APAP) overdose causes acute liver injury (ALI). Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme, and NADis oxidized type which synthesized from nicotinamide (NAM). The present study aimed to investigate the role of NADin ALI and protective property of NAM. The mice were subjected to different doses APAP. After 8 hours, the serum activities of alaninetransaminase (ALT) and aspartate aminotransferase (AST), the hepatic NADlevel and nicotinamide phosphoribosyltransferase (NAMPT) expression were determined. Then, the mice were pretreated with NAM (800 mg/kg), the hepatoprotective effects and the key antioxidative molecules were evaluated. Our findings indicated that APAP resulted in remarkable NADdepletion in a dose-dependent manner accompanied by NAMPT downregulation, and NAM pretreatment significantly elevated the NADdecline due to upregulation of NAMPT. Moreover, the downregulated Kelch-like ECH-associated protein-1 (Keap1), upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its translocation activation after NAM administration were confirmed, which were in accordance with improved superoxide dismutase (SOD) and glutathione (GSH) levels. Finally, NAM dramatically exhibited hepatoprotective effects by reducing the liver index and necrotic area. This study has suggested that APAP impairs liver NADlevel and NAM is able to improve hepatic NADto activate antioxidant pathway against APAP-induced ALI.