Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

Myocardial infarction (MI) continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10 mg/kg) and quercetin (50 mg/kg), as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) as well as cardiac contents of lipid peroxides, reduced glutathione (GSH), and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin

Isoprenaline-Induced Myocardial Infarction in Rats: Protective Effects of Hesperidin

Myocardial infarction is amongst the most common causes of death worldwide. The present study aimed to investigate the cardioprotective effect of hesperidin (200 mg/kg) either individually or in combination with atorvastatin (10 mg/kg), as a reference standard, in isoprenaline-induced myocardial infarction in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB) and serum level of cardiac troponin-I (cTn-I), oxidative stress biomarkers including cardiac contents of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) as well as serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Furthermore, ECG monitoring and histologic examinations of cardiac tissues were done. Isoprenaline increased CK-MB activity as the well the levels of cTn-I, inflammatory and oxidative stress biomarkers. In addition, it produced ST segment elevation and degenerative changes in heart tissues. The obtained data revealed that pretreatment with hesperidin alone or in combination with atorvastatin significantly decreased the elevated activity of serum CK-MB as well as serum levels of cTn-I, CRP, TNF-α and IL-10 coupled by a reduction in cardiac lipid peroxides and NO content. Moreover, both treatments resulted in marked improvement in isoprenaline-induced ECG and histopathologic changes. In conclusion, hesperidin can be regarded as a promising cardioprotective natural agent in myocardial infarction when used alone or combined with atorvastatin

Comparative study on beneficial effects of vitamins B and D in attenuating doxorubicin induced cardiotoxicity in rats: Emphasis on calcium homeostasis

The use of doxorubicin (DOX) to treat various tumors is limited by its cardiotoxicity. This study aimed to investigate and compare the cardioprotective effects of nicotinamide (NAM) and alfacalcidol (1α(OH)D3), against DOX-induced cardiotoxicity. Sprague Dawley male rats received DOX (5 mg/kg, i.p.) once/week for four consecutive weeks. Treated groups received either NAM (600 mg/kg, p.o.) for 28 consecutive days or 1α(OH)D3 (0.5 ug/kg, i.p.) once/week for four consecutive weeks. DOX elicited marked cardiac tissue injury manifested by elevated serum cardiotoxicity indices, conduction and histopathological abnormalities. Both NAM and 1α(OH)D3 successfully reversed all these changes. From the mechanistic point of view, DOX provoked intense cytosolic and mitochondrial calcium (Ca2+) overload hence switching on calpain1 (CPN1) and mitochondrial-mediated apoptotic cascades as confirmed by upregulating Bax and caspase-3 while downregulating Bcl-2 expression. DOX also disrupted cardiac bioenergetics as evidenced by adenosine triphosphate (ATP) depletion and a declined ATP/ADP ratio. Moreover, DOX upregulated the Ca2+ sensor; calmodulin kinase II gamma (CaMKII-δ) which further contributed to cardiac damage. Interestingly, co-treatment with either NAM or 1α(OH)D3 reversed all DOX associated abnormalities by preserving Ca2+ homeostasis, replenishing ATP stores and obstructing apoptotic events. Additionally, DOX prompted nuclear factor kappa B (NF-κB) dependent inflammatory responses and subsequently upregulated interleukin-6 (IL-6) expression. Co-treatment with NAM or 1α(OH)D3 effectively obstructed these inflammatory signals. Remarkably, NAM showed superior beneficial cardioprotective properties over 1α(OH)D3. Both NAM and 1α(OH)D3 efficiently attenuated DOX-cardiomyopathy mainly via preserving Ca2+ homeostasis and diminishing apoptotic and inflammatory pathways. NAM definitely exhibited effective cardioprotective capabilities over 1α(OH)D3