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.
Methods: 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.
Results: 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.
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