Abstract

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.

摘要

甲氨蝶呤（MTX）是一种细胞毒性化疗和免疫抑制剂，广泛用于治疗自身免疫性疾病和不同类型的癌症。然而，其使用受到其危及生命的副作用的限制，包括肾毒性和肝毒性。本研究的目的是探讨西他列汀对甲氨蝶呤（MTX）诱导的大鼠肾毒性的保护作用。24只大鼠被分为四组：对照组，接受媒介物6天；对照组，接受媒介物6天；对照组，接受媒介物6天。MTX 组，接受单剂 MTX，随后每日服用五剂媒介物；MTX+西他列汀组，在第一次西他列汀治疗后1小时接受单剂MTX，每日六剂西他列汀；西他列汀组接受西他列汀治疗 6 天。MTX和西格列汀均以20mg/kg体重的剂量腹腔注射。所有大鼠在研究的第七天被安乐死。收获肾组织并收集血样。评估血尿素氮（BUN）和肌酐的血清水平。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。组织病理学评估表明MTX引起显着的肾损伤。生化分析显示，MTX 组血清中 BUN 和肌酐显着升高。此外，MTX 组的肾组织氧化应激和抗氧化系统抑制也很明显。单独给药时，西他列汀不会影响这些终点，但它显着减弱了观察到的 MTX 诱导的作用。这些结果表明西格列汀对 MTX 引起的大鼠肾毒性表现出有效的抗氧化特性。