Capsaicin alleviates acetaminophen-induced acute liver injury in mice.

Overdose of N-acetyl-para-aminophenol (APAP) can induce acute liver injury (ALI). We evaluated the potential protective effect of 8-methyl-N-geranyl-6-nonamide (capsaicin (CAP)) in APAP-induced ALI in mice. ALI was induced by APAP (150 mg/kg, i.p.) administration; CAP pretreatment (1 mg/kg) was undertaken before APAP injection for 3 consecutive days. We found that CAP pretreatment attenuated ALI significantly; improve the oxidative stress-associated indicators (hepatic expression of malondialdehyde (MDA) superoxide dismutase (SOD) and glutathione (GSH)); downregulate expression of proinflammatory cytokines (interleukin (IL)-6, IL-1β, tumor necrosis factor-α) through the high-mobility group box 1/toll-like receptor-4/nuclear factor-kappa B (HMGB1/TLR4/NF-κB) signaling pathway; alleviate hepatocyte apoptosis by inhibiting expression of B-cell lymphoma-2-associated X, caspase-3 and cleaved caspase-3. CAP pretreatment reduced expression of B-cell lymphoma-2, which served as a hepatotoxic factor rather than an anti-apoptotic protein in our mouse model. We propose that CAP can alleviate APAP-induced ALI by inhibiting the inflammatory response, attenuating oxidative stress, and reducing hepatocyte apoptosis.