Melanoxetin modulates oxidative, inflammatory and apoptotic pathways to confer cardio-protection against flumethrin-induced sub-chronic toxicity.

Flumethrin (FLU) is a broad-spectrum pyrethroid that has been evidenced to cause various cardiac impairments. Melanoxetin (MEL) is a natural polyphenolic compound with diverse biological abilities. This research was executed to analyze the recuperative potential of MEL against FLU provoked sub-chronic cardiotoxicity in rats. Thirty-six Sprague Dawley rats were categorized into the control, FLU (5 mg/kg) intoxicated, FLU (5 mg/kg) + MEL (10 mg/kg) therapeutic and MEL (10 mg/kg) alone administered group. Our findings showed that FLU intoxication increased the gene expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), NLRP3, high mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), receptor for advanced glycation end-products (RAGE) interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) & interleukin-6 (IL-6) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, pro B-type natriuretic peptide (ProBNP), creatine kinase-myocardial band (CK-MB) C-reactive protein, Lactate dehydrogenase (LDH), troponin-T, Brain natriuretic peptide (BNP) and Creatine phosphokinase (CPK) were increased following the FLU intoxication. Furthermore, FLU exposure promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. FLU administration abruptly damages the morphology of heart tissues. Nonetheless, MEL therapy excellently ameliorated cardiac toxicity by virtue of its anti-inflammatory, antioxidative and anti-apoptotic potential. Collectively, MEL may serve as a cardioprotective agent in counteracting FLU provoking sub-chronic cardiotoxicity.