Exercise preconditioning and low dose copper nanoparticles exhibits cardioprotection through targeting GSK-3β phosphorylation in ischemia/reperfusion induced myocardial infarction

Background: Drinking water from copper vessels and aerobic exercise have been the known facts for cardio-protection. Our previous report explored the significant cardioprotective potential of copper and exercise training by increasing phosphorylation of GSK-3 beta and anti-oxidant potential. Objective: Present study focuses the therapeutic potential of CuNP and exercise training through their molecular interaction with GSK-3 beta, inflammatory cytokinin, oxidative stress and necrosis. Methods: The Myocardial damage was assessed by estimating the serum nitrite/nitrate concentration, increased CKMB, LDH, cTnI level, oxidative stress, inflammatory cytokinin and structural abnormalities in I/R insulted rats. Expression of Akt/pAkt and GSK-3 beta/pGSK-3 beta was measured by western blotting. Result: Treatment with CuNP (1 mg/kg/day, p.o., 4 weeks) and exercise training (swimming, 90 min/4 weeks) either alone or in combination markedly reduced I/R induced myocardial damage by attenuating biochemical and structural alteration. A significant reduction in oxidative stress and inflammatory mediators were observed in CuNP and exercise training treatment against I/R insulted rats. Moreover, improved serum NO bioavailability was observed in CuNP and exercise treated rats. Wortmannin associated blockage of cardioprotection induced by CuNP and exercise training and up-regulation of pAkt and pGSK-3 beta in I/R insulted heart confirmed the GSK-3 beta phosphorylation potential of CuNP and exercise training and -associated cardioprotection. Conclusion: Treatment with CuNP and exercise training either alone or in combination favourably phosphorylate GSK-3 beta kinase pathways and further diminish oxidative stress, inflammatory cytokines, apoptosis and increase serum bioavailability of NO in the I/R insulted rats which tends to protect myocardial damage.