Therapeutic Potential of Dihydropyridine Calcium Channel Blockers on Oxidative Injury Caused by Organophosphates in Cortex and Cerebellum: An In Vivo Study

This study was designed to investigate the effects of amlodipine (AM), a dihydropyridine calcium channel blocker, on the oxidative damage induced by diazinon (DZN) in the rat cortex and cerebellum. Forty-two rats were randomly divided into six groups. The rats were treated intraperitoneally with normal saline (group 1), AM (9 mg/kg; group 2), DZN (32 mg/kg; group 3) and different doses of AM (3, 6, and 9 mg/kg; groups 4, 5, and 6, respectively) with DZN. After 14 days, the cerebellum and cortex tissues were removed for biochemical and histological experiments. DZN significantly decreased acetylcholinesterase activity (AChE; 57%, p < 0.001 and 39.1%, p < 0.05), depleted total antioxidant capacity (TAC; 46.2%, p < 0.01 and 44.7%, p < 0.05), and increased lactate dehydrogenase activity (LDH; 96%, p < 0.001 and 202%, p < 0.001), nitric oxide (NO; 130%, p < 0.001 and 74.4%, p < 0.001), and lipid peroxidation levels (LPO; 35.6%, p < 0.001 and 128.7%, p < 0.001), in the cerebellum and cortex tissues, respectively. In addition, DZN induced structural alterations in the cerebellum and cortex. Following AM administration, a remarkable improvement was observed in LDH activity and some of the oxidative markers, such as NO and LPO; however, no significant changes were found in AChE activity when the DZN group was compared with the AM-treated groups. This study suggests that AM may prevent DZN-induced neurotoxicity via improvement of the oxidative/antioxidant balance in the cerebellum and cortex tissues.