Dietary Thymoquinone Alone or Combined with Swimming Exercise Protect against Microcystin-LR-Induced Oxidative Injury in Mice

Abstract

Microcystin-leucine-arginine (MCLR) is the most abundant cyanotoxin produced by cyanobacteria. It induces potent cytotoxicity through oxidative stress and DNA damage. Thymoquinone (TQ) is a natural nutraceutical antioxidant derived from black cumin (Nigella sativa). Physical exercise (EX) improves whole-body metabolic homeostasis. Therefore, this study examined the protective role of swimming exercise and TQ against MC-induced toxicity in mice. Fifty-six healthy adult male albino mice (25–30 g) were randomized into seven groups; group (I) was the negative control and received oral physiological saline for 21 days; group (II) received water EX for 30 min daily; group (III) was intraperitoneally injected with TQ (5 mg/kg daily, for 21 days); group (IV) was intraperitoneally administered MC (10 μg/kg daily, for 14 days) and acted as the positive toxic control; group (V) was treated with MC and water EX; group (VI) was injected with MC and TQ; finally, group (VII) was treated with MC with TQ and water EX. In comparison with the control group, the results showed hepatic, renal, and cardiac toxicity in the MCLR-treated group, indicated by a significant increase ( $p<0.05$ ) in serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transferase (ALT), cholesterol, lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase-myocardial band (CK-MB), urea, creatinine, interleukin-6, interleukin -1β, and tumor necrosis factor-α levels. In addition, there were significant elevations ( $p<0.05$ ) in malondialdehyde (MDA) and nitric oxide (NO) levels and a significant decrease in reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in hepatic, cardiac, and renal tissues. Treatment with either TQ or water EX significantly improved (p < 0.05) the MC-induced toxicity with superiority of the TQ group in the restoration of normal ranges; however, cotreatment with both TQ and swimming EX showed the most improvement and restoration to normal ranges as a result of increasing EX clinical efficacy by TQ.