Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Faculty of Pharmacy, Eastern Mediterranean University, 99628, Via Mersin 10, Famagusta, North Cyprus, Turkey.
Biol Trace Elem Res. 2023 Mar;201(3):1358-1367. doi: 10.1007/s12011-022-03249-9. Epub 2022 Apr 28.
Iron is one of the most important essential elements for cell function. However, iron overload can exert destructive effects on various tissues, especially the liver. The present study was designed to evaluate the effect of thymoquinone (TQ) on hepatotoxicity induced by iron-overload in in vitro and mouse model. After in vitro studies, thirty mice were divided into five groups, six each. Group 1 received normal saline. Group 2 received five doses of iron dextran (i.p; 100 mg/kg, one dose every 2 days). Group 3 received TQ (orally, 2 mg/kg/day). Groups 4 and 5 were administrated iron dextran saline (i.p; 100 mg/kg, one dose every 2 days) following treatment with 0.5 and 2 mg/kg/day of TQ, respectively. Based on the findings of the DPPH experiment, although TQ has significant anti-radical potential, at a safe dose of 15 × 10 nM, it reduced the IC of iron dextran on HepG2 cells by about 25%, in in vitro. Following administration of low-dose TQ (0.5 mg/kg), a significant improvement was observed in serum hepatic enzymes activity and hepatic lipid peroxidation compared to iron dextran. However, administration of TQ-high dose (2 mg/kg) led to decrease antioxidant defense alongside increased serum hepatic enzymes and pathological damages in iron dextran-treated animals. Due to the different efficacy of TQ in treatment groups, it seems that the TQ therapeutic index is low and does not have significant safety in the iron overload status.
铁是细胞功能所必需的最重要的元素之一。然而，铁过载会对各种组织，特别是肝脏，产生破坏性影响。本研究旨在评估胸腺醌（TQ）对铁过载诱导的体外和小鼠模型肝毒性的影响。体外研究后，将 30 只小鼠分为 5 组，每组 6 只。第 1 组接受生理盐水。第 2 组接受 5 次右旋糖酐铁（ip；100mg/kg，每 2 天一次）。第 3 组给予 TQ（口服，2mg/kg/天）。第 4 组和第 5 组在给予 0.5 和 2mg/kg/天的 TQ 后分别给予铁右旋糖酐盐水（ip；100mg/kg，每 2 天一次）。根据 DPPH 实验的结果，虽然 TQ 具有显著的抗自由基潜力，但在安全剂量 15×10nM 时，它将铁右旋糖酐对 HepG2 细胞的 IC 降低了约 25%。给予低剂量 TQ（0.5mg/kg）后，与铁右旋糖酐相比，血清肝酶活性和肝脂质过氧化明显改善。然而，给予 TQ 高剂量（2mg/kg）导致铁右旋糖酐处理动物的抗氧化防御能力下降，血清肝酶和病理损伤增加。由于 TQ 在治疗组中的疗效不同，TQ 的治疗指数似乎较低，在铁过载状态下没有显著的安全性。
