Background & Aim: Diallyl trisulfide (DATS) has been verified to ameliorate hepatotoxicity induced by many drugs, but the protective actions of isoniazid (INH) and rifampicin (RFP) have not been reported. We attempted to elucidate the potential effects and mechanisms of DATS against INH&RFP-caused hepatotoxicity. Methods: Male Kunming mice weighing 18-22 g were divided into 6 groups. For the hepatic-protective study, DATS (10 mg per kg, 20 mg per kg, and 40 mg per kg bw, respectively) was orally administered two hours before the INH&RFP (100 mg per kg, 100 mg per kg bw, respectively) treatments. After 11 days of treatment, 10 mice in each group were taken for the carbon clearance test, while the other 10 mice were sacrificed for the collection of serum and livers for further measurements, including the levels of serum alanine aminotransferase (ALT), aspartate transaminase (AST) and total bilirubin (T.Bili), the liver index, and liver histopathological examination. Malondialdehyde (MDA), glutathione (GSH), and the level of interleukin 1-β (IL-1-β) were measured, the carbon clearance test was performed and the immunohistochemistry of F4/80 marker for activated Kupffer cells (KCs) was analyzed to investigate potential mechanisms. Results: DATS co-administration significantly inhibited the increase of liver index and elevation of serum ALT, AST and T.Bili levels induced by INH&RFP, as well as improved the hepatocellular structure. The further mechanistic studies demonstrated that DATS co-administration counteracted INH&RFP-induced oxidative stress in mice, which was illustrated by the restoration of GSH levels, and the reduction of MDA levels in the liver. Furthermore, DATS co-administration reactivated the KCs inhibited by INH&RFP, which was illustrated by the increase of carbon phagocytosis, and the restoration of the number of activated KCs and IL-1-β levels in the liver. Conclusion: DATS effectively protected the liver against INH&RFP-induced hepatotoxicity, which might be due to its antioxidant effect and enhancement of KCs' activities.

中文翻译：

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二烯丙基三硫化物通过减少氧化应激和激活库普弗细胞，保护肝脏免受异烟肼和利福平引起的肝毒性。


背景与目的：二烯丙基三硫化物（DATS）已被证实可以改善许多药物引起的肝毒性，但异烟肼（INH）和利福平（RFP）的保护作用尚未见报道。我们试图阐明 DATS 对 INH&RFP 引起的肝毒性的潜在作用和机制。方法：雄性昆明种小鼠，体重18～22g，分为6组。对于肝脏保护研究，在 INH&RFP（分别为 100 mg/kg、100 mg/kg bw）前两小时口服 DATS（分别为 10 mg/kg、20 mg/kg 和 40 mg/kg bw）。治疗。治疗11天后，每组取10只小鼠进行碳清除试验，另10只处死小鼠，采集血清和肝脏进行进一步测定，包括血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶水平(AST)和总胆红素(T.Bili)、肝脏指数和肝脏组织病理学检查。测定丙二醛（MDA）、谷胱甘肽（GSH）和白细胞介素1-β（IL-1-β）水平，进行碳清除试验，并进行活化库普弗细胞（KCs）F4/80标记的免疫组化分析。分析以研究潜在的机制。结果：DATS合用可显着抑制INH&RFP引起的肝指数升高及血清ALT、AST、T.Bili水平升高，并改善肝细胞结构。进一步的机制研究表明，DATS 联合给药可以抵消 INH 和 RFP 诱导的小鼠氧化应激，这可以通过肝脏中 GSH 水平的恢复和 MDA 水平的降低来证明。 此外，DATS 联合给药重新激活了 INH&RFP 抑制的 KC，表现为碳吞噬作用的增加，以及肝脏中激活的 KC 数量和 IL-1-β 水平的恢复。结论：DATS能有效保护肝脏免受INH&RFP诱导的肝毒性，这可能是由于其抗氧化作用和增强KCs活性所致。