Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common adverse reaction of anti-tuberculosis drug treatment. Studies have shown that isoniazid (INH) and rifampicin (RFP) are mainly metabolized in the liver and a large amount of intracellular glutathione is used up during the metabolism of these drugs, resulting in lipid peroxidation and hepatocyte death. Ferroptosis is a novel form of programmed cell death caused by iron-ion-dependent lipid peroxidation. In this study, we explored lipid peroxidation and ferroptosis during ATB-DILI. Morphology of ferroptosis was discovered in ATB-DILI mouse livers by transmission electron microscopy. Flow cytometry was used to assess the molecular markers of lipid peroxidation and ferroptosis including reactive oxygen species, lipid peroxidation, and cellular iron content. Glutathione peroxidase 4 (GPX4) was depleted, while acyl-CoA synthetase long chain family member 4 (ACSL4) was overexpressed in the ATB-DILI tissues. And glutathione supplementation significantly reduced the level of lipid peroxidation and the risk of liver damage. Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate. In addition, iron supplementation enhanced the degree of lipid peroxidation and liver injury induced by INH and RFP in vivo and clinical retrospective study. Taken together, these results indicate that lipid peroxidation and evidence suggestive of ferroptosis occurs during ATB-DILI, and glutathione replenishment prevents this process while iron supplementation augmenting this effect.

抗结核药物性肝损伤（ATB-DILI）是抗结核药物治疗的常见不良反应。研究表明，异烟肼（INH）和利福平（RFP）主要在肝脏中代谢，并且在这些药物的代谢过程中大量细胞内的谷胱甘肽被消耗掉，从而导致脂质过氧化和肝细胞死亡。Ferroptosis是由铁离子依赖性脂质过氧化引起的程序性细胞死亡的一种新型形式。在这项研究中，我们探讨了ATB-DILI期间脂质过氧化和肥大症。通过透射电子显微镜在ATB-DILI小鼠肝脏中发现了肥大症的形态。流式细胞仪用于评估脂质过氧化和肥大症的分子标记，包括活性氧，脂质过氧化和细胞铁含量。谷胱甘肽过氧化物酶4（GPX4）被耗尽，而酰基辅酶A合成酶长链家族成员4（ACSL4）在ATB-DILI组织中过表达。补充谷胱甘肽显着降低了脂质过氧化的水平和肝损害的风险。对接受INH和RFP治疗的结核病患者进行的回顾性研究还显示，谷胱甘肽的摄入与ATB-DILI阴性之间存在关联。此外，补充铁可增强INH和RFP引起的脂质过氧化程度和肝损伤 对接受INH和RFP治疗的结核病患者进行的回顾性研究还显示，谷胱甘肽的摄入与ATB-DILI阴性之间存在关联。此外，补充铁可增强INH和RFP引起的脂质过氧化程度和肝损伤 对接受INH和RFP治疗的结核病患者进行的回顾性研究还显示，谷胱甘肽的摄入与ATB-DILI阴性之间存在关联。此外，补充铁可增强INH和RFP引起的脂质过氧化程度和肝损伤体内和临床回顾性研究。综上所述，这些结果表明在ATB-DILI期间发生了脂质过氧化和暗示有肥大症的证据，谷胱甘肽的补充阻止了这一过程，而铁的补充则增强了这种作用。