Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Drug Des Devel Ther. 2020 May 20;14:1933-1941. doi: 10.2147/DDDT.S237107. eCollection 2020.
In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection against liver damage induced by MTX in mice.
In this the mice were divided into five groups in a random manner: I) control; II) MTX (20 mg/kg); III and IV) FA (50 and 100 mg/kg) + MTX; and V) FA (100 mg/kg), and we measured serum factors, oxidative stress and inflammatory factors.
In the MTX group, accumulation of inflammatory cells, accumulation of red blood cell (RBC), and nuclear pyknosis (NP) were detected in the liver. In line with the histological data, the levels of nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α increased (TNF-α), whereas the reduced glutathione (GSH), catalase (CAT), total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) content reduced in the MTX group. However, FA ameliorated these hazardous effects in the antioxidant and anti-inflammatory systems in MTX-treated groups.
Based on our findings, oxidative stress impairment and MTX-induced liver damage were ameliorated following FA pretreatment at both histological and biochemical levels. Therefore, FA can be effectively used in abrogation of MTX-induced toxicity.
在多项研究中，氧化应激参与了甲氨蝶呤（MTX）介导的肝损伤的发病机制已得到证实。为了预防或减轻氧化应激，已经对许多药物进行了实验研究。然而，目前还没有研究评估阿魏酸（FA）对 MTX 诱导的肝损伤的影响。本研究旨在评估 FA 对 MTX 诱导的小鼠肝损伤的保护作用。
本研究将小鼠随机分为五组：I）对照组；II）MTX（20mg/kg）组；III 和 IV）FA（50 和 100mg/kg）+MTX 组；V）FA（100mg/kg）组，并检测血清因子、氧化应激和炎症因子。
在 MTX 组中，肝脏中观察到炎症细胞积聚、红细胞（RBC）积聚和核固缩（NP）。与组织学数据一致，一氧化氮（NO）、丙二醛（MDA）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平升高，而还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）、总抗氧化能力（TAC）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）含量在 MTX 组中降低。然而，FA 在 MTX 治疗组的抗氧化和抗炎系统中改善了这些有害影响。
基于我们的发现，FA 预处理可改善氧化应激损伤和 MTX 诱导的肝损伤，在组织学和生化水平上均有改善。因此，FA 可有效用于减轻 MTX 诱导的毒性。
