Malayeri Alireza, Badparva Reza, Mombeini Mohammad Amin, Khorsandi Layasadat, Goudarzi Mehdi
Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Drug Chem Toxicol. 2022 Mar;45(2):491-498. doi: 10.1080/01480545.2020.1719132. Epub 2020 Jan 28.
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.
肝毒性是甲氨蝶呤（MTX）用于治疗不同恶性肿瘤、银屑病和类风湿关节炎（RA）时的一种不良副作用。柚皮素（NAR）是一种具有多种药理特性的柑橘类黄酮。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（50mg/kg/d，口服）、第3组MTX（20mg/kg/d，腹腔注射）、第4组NAR + MTX。连续10天给予NAR，在第9天注射MTX。结果表明，MTX显著增加了肝脏中丙二醛（MDA）、一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平。另一方面，MTX的给药降低了谷胱甘肽（GSH）含量以及过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的水平。NAR的给药显著改善了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了证实。基于我们的发现，NAR可能通过清除活性自由基和诱导抗炎作用来抑制MTX诱导的肝毒性。
