Chen Mengfei, Ke Jinfang, Ma Shilan, Chai Hua, Zhang Liang, Zhang Ling
Department of Emergency, People's Hospital of Ningxia Hui Autonomous Region, Ningxia, China.
Emerg Med Int. 2022 Sep 2;2022:2791743. doi: 10.1155/2022/2791743. eCollection 2022.
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).
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）和褪黑素（MLT）对APAP诱导的肝毒性均具有减轻作用，但尚未充分阐明优化的综合治疗方法。在此，通过给野生型雄性小鼠单次注射APAP（500mg/kg），并分别联合单次注射500mg/kg NAC或100mg/kg MLT作为治疗方法，本研究旨在探究单独或联合使用NAC和褪黑素（MLT）对乙酰氨基酚（APAP）诱导的肝损伤的影响。在本研究中，NAC和MLT在APAP诱导的肝损伤中均部分具有减轻作用。然而，MLT的附加作用增强了NAC对APAP诱导的肝损伤的肝保护作用，并消除了炎症浸润。同时，两种试剂的组合减轻了谷胱甘肽（GSH）的减少和p38/JNK途径的激活。MLT和NAC的组合可进一步改善APAP诱导的肝损伤，这为药物性肝损伤（DILI）提供了一种新策略。
