Arun K Sharma1, Ashish Kumar2, Megha Sahu3, Gunjan Sharma3, Ashok K Datusalia4, Satyendra K Rajput3. 1. Cardiovascular Pharmacology Division, Department of Pharmacology, Amity University, Noida, Uttar Pradesh 201303, India. Electronic address: arunpharma2013@gmail.com. 2. Department of Nanomedicine and Pharmaceutics, Amity University, Noida, Uttar Pradesh 201303, India. 3. Cardiovascular Pharmacology Division, Department of Pharmacology, Amity University, Noida, Uttar Pradesh 201303, India. 4. National Brain Research Centre, Manesar, Gurgaon, 122 051, Haryana, India.
Abstract
BACKGROUND: Drinking water from copper vessels and aerobic exercise have been the known facts for cardioprotection. Our previous report explored the significant cardioprotective potential of copper and exercise training by increasing phosphorylation of GSK-3β and anti-oxidant potential. OBJECTIVE: Present study focuses the therapeutic potential of CuNP and exercise training through their molecular interaction with GSK-3β, 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-3β/pGSK-3β 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-3β in I/R insulted heart confirmed the GSK-3β 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-3β 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.
BACKGROUND:Drinking water from copper vessels and aerobic exercise have been the known facts for cardioprotection. Our previous report explored the significant cardioprotective potential of copper and exercise training by increasing phosphorylation of GSK-3β and anti-oxidant potential. OBJECTIVE: Present study focuses the therapeutic potential of CuNP and exercise training through their molecular interaction with GSK-3β, 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-3β/pGSK-3β 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-3β in I/R insulted heart confirmed the GSK-3β 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-3β 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.
Authors: Ying Xiao; Xin Song; Tao Wang; Xia Meng; Qipu Feng; Kui Li; Y James Kang Journal: J Cardiovasc Transl Res Date: 2021-05-17 Impact factor: 4.132