Trimetazidine Attenuates Exhaustive Exercise-Induced Myocardial Injury in Rats via Regulation of the Nrf2/NF-κB Signaling Pathway.

Hongming Zhang,Yuyan Zhang,Moyan Liu,Xiaoyan Li

doi:10.3389/fphar.2019.00175

Hongming Zhang, Yuyan Zhang + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2019.00175

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Abstract

Exhausted exercise has been reported to cause the damage of myocardial structure and function in terms of cardiomyocyte apoptosis, oxidative stress, and energy metabolism disturbance. Trimetazidine (TMZ), as an anti-ischemic agent, has been approved to be effective in promoting myocardial energy metabolism, anti-inflammatory, and anti-oxidation. However, few studies examined the effects of TMZ on myocardial injury induced by exhausted exercise. To investigate whether TMZ could ameliorate the exhaustive exercise-induced myocardial injury and explore the underlying mechanisms, here the rat model of exhaustive exercise was induced by prolonged swimming exercise and TMZ was administrated to rats before exhaustive exercise. According to the results, we demonstrated that exhaustive exercise led to cardiomyocyte damage in rats as evidenced by elevations in cTnI and NT-proBNP levels, and decrease in CX43 expression, which was attenuated by TMZ treatment. Moreover, the administration of TMZ was found to restrain exhaustive exercise-induced oxidative stress damage by increasing GSH level, SOD and GSH-Px activities, and decreasing MDA level. Additionally, TMZ ameliorated myocardial injury by inhibiting apoptosis via reducing Bax/Bcl-2 ratio and down-regulating cleaved caspase-3, cleaved PARP, and cytochrome c levels in the myocardium of rats. Furthermore, we found that TMZ suppressed oxidative stress and cardiomyocyte apoptosis via activation of Nrf2/HO-1 and inactivation of NF-κB signaling pathways. Therefore, our study suggested that TMZ provided cardioprotection in rats after exhaustive exercise, indicating TMZ might served as a potential therapeutic drug for exhaustive exercise-induced myocardial injury.

Highlights

Physical exercise is known to be essential to our health, and it has been well-described to decrease the risk of mortality in patients with cardiovascular and cerebrovascular diseases, respiratory disease, hypertension and diabetes mellitus (Reimers et al, 2012; Stanton et al, 2014)
The final weight of the rats was measured immediately after exhaustive exercise and before anesthesia, and there was no difference in body weight among the five groups
We analyzed the blood samples to measure the levels of ALT, AST, creatinine, urea, glucose, total cholesterol, triglycerides, LDLC, high-density lipoproteincholesterol (HDL-C), and lactate

Summary

Introduction

Physical exercise is known to be essential to our health, and it has been well-described to decrease the risk of mortality in patients with cardiovascular and cerebrovascular diseases, respiratory disease, hypertension and diabetes mellitus (Reimers et al, 2012; Stanton et al, 2014). Mounting evidence has showed that the functional impairment of exhaustive exercise-induced myocardial injury is associated with oxidative stress, cardiomyocyte apoptosis, inflammatory response, and mitochondrial dysfunction, and so on (Olah et al, 2015). Exhaustive exerciseinduced inflammatory response has been showed to be highly elevated along with increased inflammatory cytokines after cardiac dysfunction, which put forward an alternative mechanism of exercise-induced myocardial damage (Ali and Mann, 2004; Powers and Jackson, 2008; George et al, 2009; Muthusamy et al, 2012; Loboda et al, 2016). Numerous studies have demonstrated that excessive exercise could alter mitochondrial function and structure, and induce permanent damages in health and disease, which provides another solution for the prevention of myocardial injury after exhaustive exercise (Huang et al, 2009; Ostojic, 2016)

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