Toxicology Research Center, Medical Basic Sciences Research Institute, 48407Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Toxicology, Faculty of Pharmacy, 48407Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S603-S610. doi: 10.1177/09603271211047924. Epub 2021 Nov 22.
Due to the fact that methotrexate is widely used both as an immunosuppressive drug and as a chemotherapy agent, many studies are needed to reduce the side effects of this drug on non-target organs.
This study was designed to investigate the effects of epicatechin (Epi) on MTX (methotrexate)-induced hepatotoxicity in mice.
After 1 week for adaptation, we randomly divided 42 male Naval Medical Research Institute mice into six groups: (I) control; (II) Epi (100 mg/kg, po); (III) MTX (20 mg/kg, i.p.) on the fifth day; and (IV, V, and VI) Epi (25, 50, and 100 mg/kg, po) + MTX (20 mg/kg, i.p.) on the fifth day. At day 10, the mice were sacrificed and serum factors, oxidative stress markers, and inflammatory cytokines were measured.
MTX increased activity level of serum enzymes (alanine aminotransferase and aspartate aminotransferase), lipid peroxidation marker (malondialdehyde), and inflammatory factors including interleukin-1 beta, tumor necrosis factor-alpha, and nitric oxide. Furthermore, MTX decreased glutathione level and activity level of catalase, superoxide dismutase, and glutathione peroxidase. Epi was able to reduce the destructive effects of oxidative/antioxidant system imbalance and inflammatory reactions and also histopathological damage in MTX intoxicated mice. Epi pretreatment reduced liver dysfunction by improving the antioxidant defense system, anti-inflammatory effects, and alleviation of histopathological damage in MTX hepatotoxicity.
Accordingly, Epi can be used as a therapeutic agent in hepatotoxicity associated with MTX chemotherapy.
由于甲氨蝶呤被广泛用作免疫抑制剂和化疗药物，因此需要进行许多研究来减少该药物对非靶器官的副作用。
本研究旨在探讨表儿茶素（Epi）对 MTX（甲氨蝶呤）诱导的小鼠肝毒性的影响。
适应 1 周后，我们将 42 只雄性海军医学研究所小鼠随机分为六组：（I）对照组；（II）Epi（100mg/kg，po）；（III）第 5 天 MTX（20mg/kg，ip）；和（IV、V 和 VI）Epi（25、50 和 100mg/kg，po）+第 5 天 MTX（20mg/kg，ip）。第 10 天处死小鼠，测量血清因子、氧化应激标志物和炎症细胞因子。
MTX 增加了血清酶（丙氨酸氨基转移酶和天冬氨酸氨基转移酶）、脂质过氧化标志物（丙二醛）和炎症因子（白细胞介素-1β、肿瘤坏死因子-α和一氧化氮）的活性。此外，MTX 降低了谷胱甘肽水平和过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。Epi 能够减轻氧化/抗氧化系统失衡和炎症反应以及 MTX 中毒小鼠的组织病理学损伤的破坏性影响。Epi 预处理通过改善抗氧化防御系统、抗炎作用和减轻 MTX 肝毒性的组织病理学损伤来减轻肝功能障碍。
因此，Epi 可作为与 MTX 化疗相关的肝毒性的治疗剂。
