Potential cardioprotective effect of octreotide via NOXs mitigation, mitochondrial biogenesis and MAPK/Erk1/2/STAT3/NF-kß pathway attenuation in isoproterenol-induced myocardial infarction in rats.

ABSTRACT

Myocardial infarction (MI) is a global health care problem, which instigates irreversible cardiac tissue damage and sudden death, necessitating new prevention and management strategies. Hence, the cardioprotective effect of octreotide in MI was scrutinized by tackling the possible underlying trajectories involved. Isoproterenol (ISO)-induced acute MI model was adopted using ISO (85 mg/kg/day, S.C.) for 2 days. Rats in octreotide groups were pretreated with 20 or 40 µg/kg/day S.C. for 8 days and ISO was given on the 7th and 8th days. Octreotide showed a restoration of ECG changes, cardiac hemodynamics abnormalities, serum cardiac markers elevation (creatine kinase MB, troponin I, lactate dehydrogenase, and aspartate aminotransferase), and cardiac histoarchitecture abnormalities. In addition, octreotide pretreatment showed a significant increase in the cardiac and serum level of the diagnostic microRNA-133a. Octreotide attenuates oxidative stress indices (MDA, GSH, SOD, TAC, and HIF-1α), besides a better adjustment of NOX-1/-2/-4 expression and protein levels. Mitochondrial morphology and mtDNA copy number were preserved following the pre-treatment of Octreotide. The inflammatory pathway p38 MAPK/Erk-1/-2/p-STAT3/NF-κB pathway and the proinflammatory cytokines (TNF- α, IL-6, and IL- 1ß) were attenuated. The proapoptotic markers (cyt c, caspase-3/-9, and Bax) were also attenuated and the antiapoptotic Bcl2 marker was increased by the preadministration of octreotide. In almost all parameters, Octreotide 40 µg/kg/day was more prominent than its lower dose. Octreotide possesses dose-dependent cardioprotective properties via its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.