Razavi_2014_Drug.Chem.Toxicol_37_378

Abstract Context: Diazinon (DZN) is a widely used organophosphate insecticide. Although mechanism of DZN cardiovascular toxicity is primarily mediated through inhibition of acetylcholinesterase, however, DZN causes remarkable atropine-insensitive hypotension in rats. It has been proved that oxidative stress is an important mechanism of DZN toxicity especially in chronic exposure. Crocin, an active ingredient of saffron, has been found to antagonize the hypotensive effects of DZN in rats, but do not reverse acetylcholinesterase inhibition. OBJECTIVE: In this study the effects of DZN on contractile and relaxant responses in rat aorta as well as ex-vivo antioxidant actions of crocin have been investigated. MATERIALS AND
METHODS: Rats were divided into 7 groups: corn oil (control), DZN (15 mg/kg/day, gavage), crocin (12.5, 25 and 50 mg/kg/day, i.p.) plus DZN, vitamin E (200 IU/kg, i.p., three days a week) plus DZN and crocin (50 mg/kg/day, i.p.) groups. Treatments were continued for 4 weeks. Contractile and relaxant responses were evaluated on the isolated aorta.
RESULTS: Our results showed that DZN not only decreased the contractile responses to KCl and Phenylephrine (PE) (p < 0.001), but also attenuated the relaxant response to acetylcholine (ACh) (p < 0.01). Crocin and vitamin E attenuated lipid peroxidation, improved the reduction of contractile responses by KCl and PE and restored the decrease in ACh relaxation in rat aorta. CONCLUSION: DZN induced vascular toxicity which may be due to oxidative stress and not to a cholinergic mechanism. Crocin improved toxic effects of DZN via reducing lipid peroxidation and restoring altered contractile and relaxant responses in rat aorta.