Abstract
Quercetin (QE) is a naturally occurring flavonoid, with pleiotropic functions. Methotrexate (MTX) is a common drug widely used in human medications. MTX has side-effects that affect immunity and reproductive potency. We aimed to evaluate the protective effects of QE on the disruptions induced by MTX. A total of 32 adult male Wistar rats were allocated into four groups. The 1st group served as control (CNT); 2nd group (MTX) received MTX at 20 mg/kg body weight intraperitoneally on day 7; 3rd group (QE) received quercetin (50 mg/kg bw intra-gastrically) for two weeks; and 4th group (QE+MTX) received QE for one week followed by MTX on day 7 and continued with QE for seven days. Serum was extracted to evaluate changes in renal and liver biomarkers, immunity markers, reproductive hormones, and antioxidants levels. The testicular tissues were examined for changes in antioxidants, steroidogenesis, cytokines, and apoptosis using RT-PCR analysis. Prior administration of QE ameliorated the MTX-induced elevation in MDA and kidney and liver biomarkers. QE administration normalized MTX-induced decrease in the serum levels of IL-6, TNF-alpha, IFN-gamma, FSH, LH, and testosterone, glutathione-S-transferase (GST), SOD and catalase. MTX-intoxicated rats showed the down regulation of mRNA expression of GST, SOD, steroidogenesis-associated genes, cytokines and Bcl2. In contrast, MTX-intoxicated rats showed the upregulation of mRNA expression of Bax. The prior QE administration ameliorated and restored all gene expressions altered by MTX intoxication. We concluded that QE is a promising flavonoid that is helpful in protection against intoxication and cytotoxicity induced by MTX medications.