目的：甲氨蝶呤（MTX）是一种用于治疗癌症和自身免疫性疾病的药物；然而，由于包括肾毒性在内的严重副作用，其临床应用受到限制。本研究旨在探讨左旋蛋氨酸（L-Met）对MTX毒性大鼠肾脏的保护作用。方法：将30只雄性大鼠平均分为5组：对照组（生理盐水）、Met400（400 mg/kg L-Met） ）、MTX（20 毫克/千克 MTX）、MTX-Met300（300 毫克/千克 L-Met 和 20 毫克/千克 MTX）和 MTX-Met400（400 毫克/千克 L-Met 和 20 毫克/千克 MTX）。最后一次给药一天后（第16天）对大鼠实施安乐死，并收集血清和肾组织样本。评估肾功能和损伤指数、氧化应激/抗氧化指数和促炎细胞因子。结果：结果表明，L-Met 可以通过改善大部分测试参数，以剂量相关的方式有效抵消 MTX 的肾毒性作用。此外，较高剂量的 L-Met 能够将多个参数恢复到正常水平。此外，对MTX引起的血液学变化的研究揭示了L-Met的纠正潜力。结论：由于其抗氧化和抗炎作用，L-Met可以成为调节与MTX相关的肾毒性的有效辅助疗法。

Objective: Methotrexate (MTX) is a drug used in the treatment of cancer and autoimmune disorders; however, its clinical use is limited because of serious side effects including renal toxicity. This study aimed to investigate the protective effect of Lmethionine (L-Met) on MTX toxicity in the kidneys of rats.Methods: Thirty male rats were divided equally into five groups: control (saline), Met400 (400 mg/kg L-Met), MTX (20 mg/kg MTX), MTX-Met300 (300 mg/kg L-Met and 20 mg/kg MTX), and MTX-Met400 (400 mg/kg L-Met and 20 mg/kg MTX). Rats were euthanized one day after the last dose administration (day 16) and serum and renal tissue samples were collected. Renal function and injury indices, oxidative stress/antioxidant indices and proinflammatory cytokines were evaluated.Results: The results showed that L-Met could effectively counteract the nephrotoxic effects of MTX, in a dose-related manner, by improving most of the tested parameters. Furthermore, the higher dose of L-Met was able to restore several parameters to normal levels. In addition, investigation of MTX-induced hematological changes revealed a corrective potential of L-Met.Conclusion: L-Met can be an effective adjuvant therapy to modulate renal toxicity associated with MTX because of its antioxidant and antiinflammatory effects.