Abstract
IntroductionMyocardial 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. AimThe 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. MethodsRats 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. ResultsThe 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. ConclusionTQ 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.
Highlights
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
Heart sections obtained from the ISP-treated group showed histological alterations in the form of myocardial cell separation caused by interstitial edema, wavy fibers, as well as inflammatory leukocyte infiltration, Figures 2 B&C&D
The results of our study demonstrated that the administration of TQ for 21 days before and at the same time of MI induction showed a significant decline in serum cardiac biomarkers and cardiac lipid peroxidation levels, together with significant improvement in cardiac antioxidant activities and levels
Summary
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). MtDNA content, oxidative stress parameters (MDA, GSH, SOD, GPx, and CAT), inflammatory mediators (IL-6, IL-1β, and TNF-α), and apoptosis markers (BAX, Bcl, and caspase-3) were detected. Results: The results showed that pre- and co-treatment with TQ in the (TQ þ 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. The inflammatory response in MI includes increased expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which causes an increase in cytokines, chemokines, and adhesion molecules. It causes gene upregulation of Interleukin 1-β (IL-1β), the gatekeeper of the process of inflammation [9] together with interleukin-6 (IL-6) which decreases the basal contractility of the myocytes accompanied by the affection of beta-adrenergic receptor responsiveness [10]
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