Cardiovascular Toxic Effects of Chlorpyrifos: A Possible Protective Role for Pomegranate Extracts

Objectives: Present study aimed to investigate if prolonged intake of either pomegranate peel methanolic extract (PPME) or pomegranate juice (PJ) could protect against CPF-induced cardiotoxicity and restore cardiac functions up to normal status. Methods: Thirty six male albino rats (170-180 g) were equally allocated into 6 groups, the first four ones were used as control, PJ (3 ml/kg), PPME (200 mg/kg) and CPF (6.75 mg/kg) groups, while the two last groups were given CPF+PJ and CPF+PPME at the same mentioned doses, daily for 60 successive days. Results: CPF-exposed group showed electrocardiograph (ECG) alterations, manifested as ST segment elevation, prolonged corrected QTc interval and shortened RR interval, along with elevation in heart rate and blood pressure. Further elevation in cardiac marker enzymes (CK-MB, LDH) and myocardium specific troponin isoform (cTn 1) were noticed. Results also showed decreased cardiac antioxidants (GSH, SOD), and increased malondialdhyde (MDA) level with induction of apoptosis and cell cycle arrest, evidenced by increased cardiac p53, caspase-3, Bax and G0/G1 phase% with decreased Bcl-2, S- and G2/M phases%. Cardiac histopathological changes characterized by disorganization and degeneration in myocardial fibers with cytoplasmic vacuolization and separation of cardiac myofibrils were observed. Congested thickened arteries with extravasation of the blood in between the cardiac myofibrils were also noticed following CPF exposure. On contrast, co-administration of CPF and either PJ or PPME tended to protect against CPF-induced cardiotoxicity, as manifested by improved ECG alterations, oxidative status apoptotic biomarkers and histological characters. Conclusion: Thus, administration of PPME or PJ seems to offer a greater protective effect against CPF-induced myocardial injury, probably through the synergism between their antioxidant and anti-apoptotic properties.