Abstract

Hepatotoxicity is an adverse side effect of methotrexate (MTX) administration for the treatment of different malignancies, psoriasis, and rheumatoid arthritis (RA). Naringenin (NAR) is a citrus flavone with multiple pharmacological characteristics. In this study, we aimed to investigate the protective effects of NAR on MTX-induced hepatotoxicity in rats. For this purpose, 32 Wistar rats were randomly divided into four experimental groups as group 1 Control, group 2 NAR (50 mg/kg/d, o.p.), group 3 MTX (20 mg/kg/d, i.p.), group 4 NAR + MTX. NAR was administrated for 10 consecutive days and MTX was injected on the ninth day. The results indicated that MTX significantly increased malondialdehyde (MDA), NO, TNF-α, and IL-6 levels in the liver. On the other hand, administration of MTX reduced the GSH content, as well as CAT, SOD, and GPx levels. NAR administration remarkably improved MTX-induced alteration of biochemical biomarkers. Our findings were confirmed by the histopathological examination of the liver. Based on our findings, NAR may inhibit MTX-induced hepatotoxicity through scavenging reactive free radicals and inducing anti-inflammatory effects.

摘要

肝毒性是甲氨蝶呤 (MTX) 用于治疗不同恶性肿瘤、银屑病和类风湿性关节炎 (RA) 的不良副作用。柚皮素 (NAR) 是一种具有多种药理特性的柑橘黄酮。在本研究中，我们旨在研究 NAR 对 MTX 诱导的大鼠肝毒性的保护作用。为此，将 32 只 Wistar 大鼠随机分为四个实验组，即第 1 组对照组、第 2 组 NAR (50 mg/kg/d, op)、第 3 组 MTX (20 mg/kg/d, ip)、第 4 组 NAR + MTX。NAR连续给药10天，第9天注射MTX。结果表明，MTX 显着增加肝脏中丙二醛 (MDA)、NO、TNF-α 和 IL-6 的水平。另一方面，MTX 的施用降低了 GSH 含量，以及 CAT、SOD 和 GPx 水平。NAR 给药显着改善了 MTX 诱导的生化生物标志物的改变。我们的发现通过肝脏的组织病理学检查得到证实。根据我们的研究结果，NAR 可能通过清除反应性自由基和诱导抗炎作用来抑制 MTX 诱导的肝毒性。