Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-indu
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ORIGINAL ARTICLE
Protective effects of apigenin on altered lipid peroxidation, inflammation, and antioxidant factors in methotrexate-induced hepatotoxicity Mehdi Goudarzi 1 & Mojtaba Kalantar 2 & Elahe Sadeghi 3 & Mojtaba Haghi Karamallah 2 & Hadi Kalantar 1,4 Received: 18 May 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Methotrexate (MTX) is used as an effective chemotherapeutic agent against autoimmune diseases and tumors. Oxidative stress and inflammation are involved in the pathogenesis of MTX-induced damage. This study aimed at examining the ameliorating effects of apigenin (API) as a natural antioxidant on MTX-induced hepatotoxicity. The rats were classified into four groups: group I: normal saline-treated, group II: MTX-treated (20 mg/kg, ip, single dose at day 7), group III: MTX + API–treated (20 mg/kg, po), and group IV: API-treated. API was administrated for 9 days. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were used as biochemical factors of MTX-induced hepatic injury. In hepatic tissues, the levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as oxidative stress markers along with inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) were assessed. Our results showed that MTX administration significantly increased ALP, ASP, ALT, MDA, NO, TNF-α, and IL-1β levels and significantly decreased antioxidant factors such as GSH, CAT, GPx, and SOD. The API pretreatment group showed a significant rise in hepatic antioxidant markers, besides significant reductions in the serum levels of AST, ALT, and ALP and hepatic content of MDA, TNF-α, NO, and IL-1β. In addition, the hepatoprotective effect of API was confirmed by histological evaluation of the liver. API can prevent MTX-induced hepatotoxicity through mitigation of oxidative stress and inflammation. Keywords Methotrexate . Apigenin . Hepatotoxicity . Oxidative stress . Inflammation
Introduction Drug-induced injury of the liver is considered a significant problem in the course of pharmacotherapy (Hytiroglou et al. 2004). Methotrexate (MTX), a folic acid antagonist, has major applications in the treatment of tumors, inflammatory disorders, and autoimmune disorders, such as rheumatoid arthritis * Hadi Kalantar [email protected] 1
Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2
Faculty of Medicine, Shoushtar University of Medical Sciences, Shoushtar, Iran
3
Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4
Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
and multiple sclerosis (Herfarth 2016; Hytiroglou et al. 2004). On the other hand, liver toxicity is a serious side effect of MTX treatment, which can range fro
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