Cardiovascular Pharmacology Division, Department of Pharmacology, Amity University, Noida, Uttar Pradesh, India.
Department of Nanomedicine and Pharmaceutics, Amity University, Noida, Uttar Pradesh, India.
Pharmacol Rep. 2018 Aug;70(4):789-795. doi: 10.1016/j.pharep.2018.02.023. Epub 2018 Feb 24.
Myocardial infarction (MI) is a solitary fatal condition with towering prevalence of mortality worldwide. Our previous study reports that low-dose copper nanoparticles (CuNP) can halt the progression of diabetes-induced cardiotoxicity as copper has anti-inflammatory, anti-proliferative and anti-oxidant potential. In addition, exercise training has also been considered a hallmark for cardiac health.
Cardioprotective potential of CuNP (1mg/kg/day, po, 4 weeks) and exercise (swimming, 90min, 5days/4 weeks) either alone or in combination was estimated by measuring the surge in serum nitrite/nitrate concentration and reduction in creatine kinase MB (CKMB), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), lipid profile, oxidative stress, structural abnormalities against isproterenol (ISO)-induced MI.
ISO significantly increased CKMB, LDH, cTnI, lipid alteration, oxidative stress, structural abnormalities and decrease nitrite/nitrate concentration in serum. Quantitative estimation of total and phosphorylated Akt(SER-473)/GSK-3b(SER-9) indicated the significant reduction in pAkt and pGSK-3b in ISO treated animal. Individual and combined treatment of CuNP and exercise significantly reduce ISO -induced CKMB, cTnI, LDH, and improve nitrite/nitrate concentration and lipid profile. Attenuation of myocardial oxidative stress and serum TBARS revealed the associated preconditioning effect of exercise and CuNP against oxidative stress. Exercise and CuNP also showed the protective potential against structural abnormalities. However, the cardioprotective effect of individual and combined strategy of exercise and CuNP was vanished by wortmannin and also avoid the downregulation of pGSK-3b.
Low-dose CuNP and exercise training significantly prevents ISO-induced MI through preconditioning and GSK-3b inhibition. Ability to upsurge the NO level, lipid profile and reduced oxidative stress improve the potency of combined strategy.
心肌梗死(MI)是一种致命的疾病,在全球范围内死亡率居高不下。我们之前的研究报告称,低剂量铜纳米粒子(CuNP)可以阻止糖尿病引起的心脏毒性的发展,因为铜具有抗炎、抗增殖和抗氧化的潜力。此外,运动训练也被认为是心脏健康的标志。
通过测量血清中亚硝酸盐/硝酸盐浓度的增加和肌酸激酶同工酶 MB(CKMB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白 I(cTnI)、脂质谱、氧化应激、结构异常的降低,来评估 CuNP(1mg/kg/天,口服,4 周)和运动(游泳,90 分钟,每周 5 天/4 周)单独或联合的心脏保护潜力,以对抗异丙肾上腺素(ISO)诱导的 MI。
ISO 显著增加了 CKMB、LDH、cTnI、脂质改变、氧化应激、结构异常,并降低了血清中亚硝酸盐/硝酸盐浓度。总和磷酸化 Akt(SER-473)/GSK-3b(SER-9)的定量估计表明,在 ISO 处理的动物中,pAkt 和 pGSK-3b 显著减少。CuNP 和运动的单独和联合治疗显著降低了 ISO 诱导的 CKMB、cTnI、LDH,并改善了硝酸盐/硝酸盐浓度和脂质谱。心肌氧化应激和血清 TBARS 的衰减表明运动和 CuNP 对氧化应激具有相关的预处理作用。运动和 CuNP 也显示出对结构异常的保护潜力。然而,单独和联合应用运动和 CuNP 的心脏保护作用在wortmannin 存在下消失,并且避免了 pGSK-3b 的下调。
低剂量的 CuNP 和运动训练通过预处理和 GSK-3b 抑制显著预防 ISO 诱导的 MI。提高 NO 水平、脂质谱和降低氧化应激的能力增强了联合策略的效力。