Savran M, Cicek E, Doguc D K, Asci H, Yesilot S, Candan I A, Dagdeviren B, Cankara F N, Oncu M, Uğuz A C, Ozer M K
1 Provincial Directorate of Health, Republic of Turkey Ministry of Health , Antalya, Turkey.
2 Department of Pharmacology, School of Medicine, Süleyman Demirel University , Isparta, Turkey.
Physiol Int. 2017 Jun 29:1-11. doi: 10.1556/2060.104.2017.2.5.
Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.
与其他几种抗癌药物一样，甲氨蝶呤（MTX）会引起副作用，如神经性疼痛、肝毒性和肾毒性。活性氧的异常产生被怀疑与MTX诱导的肝肾毒性的病理生理学有关。因此，本研究的目的是探讨维生素C（Vit C）对MTX诱导的大鼠肝脏和肾脏组织氧化应激的可能保护作用。总共32只大鼠被随机且平均分为四组。第一组作为对照组。第二组腹腔注射单剂量20mg/kg的MTX。为了验证我们的假设，第三组和第四组通过口服灌胃给予250mg/kg的Vit C，持续3天，分别为有或无MTX治疗。在研究结束时，收集大鼠的肝脏和肾脏组织并进行组织学检查。对两种组织均检测丙二醛浓度以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性。在肝脏和肾脏组织中，MTX使脂质过氧化水平升高，而SOD、CAT和GSH-Px水平降低。给予Vit C 3天后，所有参数，包括肝组织中的CAT水平，均得到显著恢复。与生化结果相似，通过组织病理学检查在两种组织中均检测到氧化损伤的证据。从本研究结果中，我们能够观察到给予Vit C可调节抗氧化氧化还原系统，并降低MTX诱导的肾脏和肝脏氧化应激。Vit C可改善MTX对大鼠肝脏和肾脏组织的毒性作用。
