Alum Esther U, Famurewa Ademola C, Orji Obasi U, Aja Patrick M, Nwite Felix, Ohuche Simon E, Ukasoanya Stanley C, Nnaji Lucy O, Joshua Deborah, Igwe Kingsley U, Chima Stephen F
Department of Biochemistry, Faculty of Science, Ebonyi State University, PMB, 053, Abakaliki, Nigeria.
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria.
Avicenna J Phytomed. 2023 Jul-Aug;13(4):377-387. doi: 10.22038/AJP.2023.21903.
Methotrexate (MTX) is a frontline antimetabolite anticancer drug which is used in different cancer treatments but its nephrotoxicity is a notable drawback that limits its clinical use. The present study was undertaken to examine whether leaf extract (DSLE) could block MTX nephrotoxic side effect in rats.
Animals were divided randomly into Control, Ethanol extract, MTX, and Extract + MTX groups. DSLE (200 mg/kg bw) was orally administered for 21 days, while MTX was injected intraperitoneally (ip) on the 18 day. Serum levels of urea, creatinine and uric acid were determined. Kidney samples were used to determine glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities, and renal levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and caspase-3.
Injection of MTX resulted in considerable increases (p<0.05) in creatinine, urea, and uric acid levels as well as renal MDA, NO, IL-6, TNF-α and caspase-3 compared to the controls. SOD and GPx increased significantly, while GSH was significantly depleted. Interestingly, DSLE markedly reduced (p<0.05) levels of creatinine, urea, uric acid, TNF-α, NO, MDA and caspase-3, whereas renal GSH increased markedly compared to the MTX group.
DSLE has nephroprotective activity against MTX toxicity. However, further mechanistic studies are needed.
甲氨蝶呤（MTX）是一种一线抗代谢抗癌药物，用于不同的癌症治疗，但其肾毒性是一个显著缺点，限制了其临床应用。本研究旨在探讨龙葵叶提取物（DSLE）是否能阻断大鼠MTX的肾毒性副作用。
将动物随机分为对照组、乙醇提取物组、MTX组和提取物+MTX组。DSLE（200mg/kg体重）口服给药21天，而MTX在第18天腹腔注射（ip）。测定血清尿素、肌酐和尿酸水平。使用肾脏样本测定谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性，以及肾脏中丙二醛（MDA）、还原型谷胱甘肽（GSH）、一氧化氮（NO）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和半胱天冬酶-3的水平。
与对照组相比，注射MTX导致肌酐、尿素和尿酸水平以及肾脏MDA、NO、IL-6、TNF-α和半胱天冬酶-3显著升高（p<0.05）。SOD和GPx显著增加，而GSH显著减少。有趣的是，与MTX组相比，DSLE显著降低（p<0.05）肌酐、尿素、尿酸、TNF-α、NO、MDA和半胱天冬酶-3的水平，而肾脏GSH显著增加。
DSLE对MTX毒性具有肾保护活性。然而，需要进一步的机制研究。
