Trimetazidine (TMZ) is a promising emerging therapeutic piperazine derivative for renal pathologies. However, the nephroprotective mechanism of TMZ against heavy metal-induced toxicity is unknown. This study, therefore, aimed to explore whether TMZ could mitigate mercury-induced nephrotoxicity in rats. Rats were injected TMZ (3 mg/kg bw) and/or mercury chloride (HgCl2) (4 mg/kg bw) for 4 days (n = 6 rats per group). The blood analysis revealed marked increases in creatinine, urea and uric acid levels in HgCl2 group compared to the control. HgCl2 induced prominent decreases in renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx) activities compared to the control followed by marked increases in the levels of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3 and caspase-9. Whereas the renal levels of anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) reduced considerably compared to the control. Contrarily, it was found that in the rats administered TMZ + HgCl2, levels of renal markers, MDA, TNF-α, IL-6 and caspases-3/-9 were prominently reduced compared to the HgCl2 group. The renal SOD, CAT, GPx, IL-4, and IL-10 were markedly elevated along with ameliorated histopathological lesions. On the whole, therefore, TMZ could be repurposed for blocking HgCl2 nephrotoxicity via inhibition of oxidative inflammation and apoptosis in rats.
Keywords: Mercury; antioxidant; piperazine; renal toxicity; trimetazidine.