OBJECTIVE: Aim: To clarify the potential cardioprotective effect of Trimetazidine against experimentally sepsis-caused endotoxic cardiac injury damage in mice. PATIENTS AND METHODS: Materials and Methods: 24 Mice were divided into four groups (n=6): Sham group, CLP group DMSO group, trimetazidine-treated group 50 mg/kg IP, 1hr before CLP, then the animals were sacrificed 24 hr after CLP and tissue sample was taken for measurement of TNF-α, TNF-αr1, IL-1β, HO-1, MPO, caspase-11, F2-isoprostane and serum troponin by ELISA and gene expression of AMPK-Nrf2 by qpcr and histopathological study. RESULTS: Results: trimetazidine treated group showed significant changes as compared with clp group regarding TNF-α, TNF-αr1, IL-1β, HO-1, MPO, CASPASE-11, F2-ISOPROSTANE as well as affect tissue mRNA expression of AMPK-Nrf2 genes p<
0.05. CONCLUSION: Conclusions: We evaluate that Trimetazidine has cardio protective effects due to its anti-inflammatory and anti-oxidative action. Also, trimetazidine showed a cardio-protective effect as they affect tissue mRNA expression of AMPK-Nrf2 genes.