Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.
Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran.
J Environ Sci Health C Toxicol Carcinog. 2023;41(1-2):22-35. doi: 10.1080/26896583.2023.2186683. Epub 2023 Apr 3.
Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.
甲氨蝶呤（MTX）是一种细胞毒性化疗药物和免疫抑制剂，广泛用于治疗自身免疫性疾病和不同类型的癌症。然而，其使用受到危及生命的副作用的限制，包括肾毒性和肝毒性。本研究旨在探讨西他列汀对 MTX 诱导的大鼠肾毒性的保护作用。24 只大鼠分为四组：对照组，给予载体 6 天；MTX 组，单次给予 MTX，随后给予载体 5 天；MTX+西他列汀组，单次给予 MTX 后 1 小时给予西他列汀首次治疗，并给予西他列汀 6 天；西他列汀组，给予西他列汀 6 天。MTX 和西他列汀均以 20mg/kg 体重的剂量腹腔注射。所有大鼠均在研究第 7 天处死。采集肾脏组织和血液样本。评估血清中血尿素氮（BUN）和肌酐水平。此外，还测定了肾组织中的过氧化氢酶、谷胱甘肽过氧化物酶、超氧化物歧化酶活性和丙二醛（MDA）水平。此外，还进行了组织病理学分析。组织病理学评价显示 MTX 诱导的肾脏损伤明显。生化分析显示 MTX 组血清中 BUN 和肌酐明显升高。此外，MTX 组肾组织氧化应激和抗氧化系统抑制明显。西他列汀单独给药时对这些终点没有影响，但显著减轻了观察到的 MTX 诱导的作用。这些结果表明，西他列汀对 MTX 诱导的大鼠肾毒性具有显著的抗氧化作用。
