Acetaminophen (APAP) overdose is one of the leading causes of acute liver damage. Given N-acetylcysteine (NAC) and melatonin (MLT) both have an attenuated value for APAP-induced liver toxification, where an optimized integrated treatment has not been well deciphered. Here, by giving a single dose of APAP (500 mg/kg) to wild-type male mice, combined with a single dose of 500 mg/kg NAC or 100 mg/kg MLT separately as the therapeutic method, this study aimed to investigate the effects of NAC and melatonin (MLT) alone or combined on acetaminophen (APAP)-induced liver injury. In this study, NAC and MLT both partially have an alleviated function in APAP-challenged liver injury. However, MLT’s add-on role strengthens the hepatoprotective effect of NAC on APAP-induced liver damage and resolute the inflammatory infiltration. Meanwhile, the combination of two reagents attenuates the decreased glutathione (GSH) and activation of the p38/JNK pathway. The combination of MLT and NAC can further ameliorate APAP-induced liver injury, which provides a novel strategy for drug-induced liver injury (DILI).

中文翻译：

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褪黑激素与 N-乙酰半胱氨酸的应用超过了对乙酰氨基酚诱导的肝毒性的传统治疗

对乙酰氨基酚（APAP）过量是急性肝损伤的主要原因之一。鉴于 N-乙酰半胱氨酸 (NAC) 和褪黑激素 (MLT) 都对 APAP 诱导的肝中毒具有减弱的价值，其中优化的综合治疗尚未得到很好的破译。在这里，通过给野生型雄性小鼠单剂量 APAP (500 mg/kg)，联合单剂量 500 mg/kg NAC 或 100 mg/kg MLT 作为治疗方法，本研究旨在调查NAC和褪黑激素（MLT）单独或联合对对乙酰氨基酚（APAP）诱导的肝损伤的影响。在这项研究中，NAC 和 MLT 在 APAP 挑战的肝损伤中均具有部分缓解功能。然而，MLT 的附加作用增强了 NAC 对 APAP 引起的肝损伤的保肝作用，并解决了炎症浸润。同时，两种试剂的组合减弱了降低的谷胱甘肽 (GSH) 和 p38/JNK 通路的激活。MLT与NAC联合使用可进一步改善APAP诱导的肝损伤，为药物性肝损伤（DILI）提供了新的策略。