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.

过量的N-乙酰对-氨基酚（APAP）可以诱发急性肝损伤（ALI）。我们评估了在小鼠APAP诱导的ALI中8-甲基-N-香叶基-6-壬酰胺（辣椒素（CAP））的潜在保护作用。ALI是通过APAP（150 mg / kg，ip）给药诱导的；在连续3天进行APAP注射之前，进行了CAP预处理（1 mg / kg）。我们发现，CAP预处理可显着降低ALI；改善氧化应激相关指标（丙二醛（MDA）超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的肝表达）；通过高迁移率族盒1 / toll样受体-4 /核因子κB（HMGB1 / TLR4 / NF）下调促炎细胞因子（白介素（IL）-6，IL-1β，肿瘤坏死因子-α）的表达-κB）信号通路；通过抑制B细胞淋巴瘤2相关X的表达来减轻肝细胞凋亡，caspase-3和裂解的caspase-3。CAP预处理可降低B细胞淋巴瘤2的表达，而B细胞淋巴瘤2在我们的小鼠模型中是一种肝毒性因子而不是抗凋亡蛋白。我们建议，CAP可以通过抑制炎症反应，减轻氧化应激和减少肝细胞凋亡来减轻APAP诱导的ALI。