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Abstract Methotrexate (MTX) is an anti-folate drug used to treat cancer and some inflammatory diseases (such as rheumatoid arthritis and psoriasis). The efficacy of MTX is often limited by its severe toxicity. Propolis (bee glue) is one of the most significant bee products that has an important role in balancing antioxidant systems and has an anti-peroxidant effect on several tissues. The present study was conducted to investigate the ameliorative effect of propolis (PP) extract against oxidative damage of MTX on blood and liver, kidney and brain tissues in rats. One hundred and twenty male Wistar albino rats with mean body weights 90 g ± 5 g were divided into 5 groups. Control group (G1), Saline + DMSO group (G2), propolis extract group (G3), MTX group (G4) and MTX plus propolis extract co-administered group (G5). Rats were administered their respective doses of propolis extract and/or MTX for 3, 6 and 9 weeks intervals. The results showed that the MTX significantly reduced hemoglobin concentration (Hb), hematocrit % (Hct), mean corpuscular hemoglobin concentration (MCHC), red blood cell count (RBCs), white blood cell count (WBCs) and platelet s count. While significantly increased mean corpuscular volume (MCV) and lymphocytes %. Moreover, MTX caused significant increase of malondialdehyde (MDA) level and significant decrease in reduced glutathione (GSH) concentration and antioxidant enzyme activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR)) in liver and brain tissues as compared to control group (G 2) in a time dependent manner. MTX administration also caused significant increase in serum amino transferase AST, ALT and alkaline phosphatase (ALP) activities in a time dependent manner, but a significant increase in total bilirubin only in 9 weeks as compared to control group (G2). On the other hand, MTX impaired kidney function as reflected by a significant increase in serum urea and creatinine levels and decrease in serum uric acid level as compared to control group (G 2). Results suggested that co -administration of propolis with MTX (G5) normalized all these altered parameters as compared to MTX-treated group in the three different time intervals. Propolis extract administration also recovered the structural and functional integrity of the hepatic cells. Data showed that long term administration of MTX for 9 weeks produce maximum damage over 6 or 3 weeks, whereas, propolis administration in combination with MTX for 9 weeks offers better alleviation over 6 or 3 weeks. Key words: Methotrexate, Propolis extract, Oxidative damag |