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Thymoquinone protects against cardiac mitochondrial DNA loss, oxidative stress, inflammation and apoptosis in isoproterenol-induced myocardial infarction in rats.

ABSTRACT:

Introduction

Myocardial infarction (MI) is an ischemic life-threatening disease with exaggerated oxidative stress state that vigorously damages the cardiomyocyte membrane and subcellular structures, including the vital mitochondrial DNA (mtDNA). The mtDNA is responsible for the proper functionality of the mitochondria, which are abundant in cardiomyocytes due to their dynamic nature and energy production requirements. Furthermore, oxidative stress triggers an inflammatory cascade and eventual apoptosis, which exacerbates cardiac injuries and dysfunction.

Aim

The present study used an isoproterenol (ISP)-induced MI rat model to investigate the role of the main active constituent of Nigella Sativa seeds, thymoquinone (TQ), in preserving the cardiac mtDNA content and ameliorating oxidative stress, inflammation, and apoptosis.

Methods

Rats in the (TQ + ISP) group were pre-treated with TQ (20 mg/kg/day) for 21 days before the MI induction using ISP (85 mg/kg/day). In addition, negative control and ISP groups were included in the study for comparison. A histopathological examination was performed and serum cardiac parameters (cTnI and LDH) were assessed. In addition, mtDNA content, oxidative stress parameters (MDA, GSH, SOD, GPx, and CAT), inflammatory mediators (IL-6, IL-1β, and TNF-α), and apoptosis markers (BAX, Bcl2, and caspase-3) were detected.

Results

The results showed that pre- and co-treatment with TQ in the (TQ + ISP) group reversed the histoarchitecture changes, caused a significant decrease in serum cardiac markers, oxidative stress markers, inflammatory cytokines, the apoptosis process, and preserved the cardiac mtDNA content.

Conclusion

TQ is a cardioprotective agent with an extended effect on preserving the cardiac mtDNA content, in addition to its powerful antioxidant, anti-inflammatory, and anti-apoptotic action.

SUBMITTER: Khalifa AA

PROVIDER: S-EPMC8322274 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPreclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans.Methods and resultsOverall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI.ConclusionsThe presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254.