Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure.

This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats. Rats were divided into 7 groups; control (corn oil, gavage), DZN (15 mg/kg/day, gavage,), crocin (12.5, 25 or 50 mg/kg/day, i.p) plus DZN, vitamin E (200 IU/kg, i.p, three times per week) plus DZN and crocin (50 mg/kg/day, i.p) groups. Treatments were continued for 4 weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR. DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50 mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.