Protective mechanisms of piperine against acetaminophen-induced hepatotoxicity may be mediated through TGFBRAP1.

To investigate the possible protective mechanisms of piperine against acetaminophen (APAP)-induced hepatotoxicity in mice.Mice were given APAP (650 mg/kg i.p. once) with or without pretreatment with piperine (50 mg/kg/day orally for 3 days).APAP caused liver toxicity as indicated by increased serum alanine aminotransferase and liver microscopic pathology, decreased hepatic superoxide dismutase and glutathione reductase activities, without affecting nuclear factor erythroid 2-related factor 2 (Nrf2) expression. APAP administration induced inflammation and apoptosis manifested as increased NF-κB p65 and dysregulation of caspase 3/Bcl2 expression, respectively. In addition, APAP increased the expression of transforming growth factor-β receptor-associated binding protein 1 (TGFBRAP1). On the other hand, pretreatment with piperine improved liver function and structure, reserved hepatic antioxidative defense, and attenuated inflammatory and apoptotic markers. Interestingly, piperine administration enhanced hepatic TGFBRAP1 expression compared to APAP alone.The hepatoprotective effects of piperine against APAP are mediated via its antioxidant, anti-inflammatory, and anti-apoptotic effects, in addition to regulation of TGFBRAP1.