Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt.
Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Aug;393(8):1405-1417. doi: 10.1007/s00210-020-01843-z. Epub 2020 Feb 26.
Hesperidin (HD), a bioflavonoid, has been shown to exert hepatoprotective effects. Our aim is to investigate the possible protective effects of HD against methotrexate (MTX) hepatotoxicity in adult male Sprague-Dawley (SD) rats that were divided into four groups (10 rats/each) and were exposed to MTX with or without HD co-administration for consecutive 28 days. The results showed that HD significantly ameliorated MTX-induced increase in liver enzymes and histopathological changes. Hepatic oxidative stress was suppressed by HD, as evidenced by the decrease in malondialdehyde (MDA), with a concomitant increase in total antioxidant activity (TAC), catalase (CAT), and glutathione (GSH) levels. Moreover, co-administration of HD with MTX remarkably upregulated the expression of Nrf2 and HO-1 compared with the MTX group. By the decrease in nuclear factor-kB (NF-κB) pathway and tumor necrosis factor α (TNF-α), HD obviously attenuated inflammatory response in MTX-lesioned livers. Likewise, the downregulation of P53 by HD could explain its antiapoptotic effects as indicated by increase BCl2 and the significant decrease of caspase-9 mRNA expression as compared with the MTX group. Thus, these findings revealed the hepatoprotective nature of HD against MTX hepatotoxicity by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant aptitude.
橙皮苷（HD）是一种生物类黄酮，已被证明具有保肝作用。我们的目的是研究 HD 对成年雄性 SD 大鼠甲氨蝶呤（MTX）肝毒性的可能保护作用，这些大鼠分为四组（每组 10 只），连续 28 天接受 MTX 加或不加 HD 联合治疗。结果表明，HD 显著改善了 MTX 诱导的肝酶升高和组织病理学变化。HD 抑制肝氧化应激，表现为丙二醛（MDA）降低，同时总抗氧化活性（TAC）、过氧化氢酶（CAT）和谷胱甘肽（GSH）水平升高。此外，与 MTX 组相比，HD 与 MTX 联合给药可显著上调 Nrf2 和 HO-1 的表达。通过降低核因子-κB（NF-κB）途径和肿瘤坏死因子-α（TNF-α），HD 明显减轻了 MTX 损伤肝脏的炎症反应。同样，HD 下调 P53 可解释其抗凋亡作用，表现为 BCl2 增加，与 MTX 组相比，caspase-9 mRNA 表达显著降低。因此，这些发现表明 HD 通过减轻促炎和凋亡介质并改善抗氧化能力对 MTX 肝毒性具有保肝作用。
