Effect of chronic organophosphate exposure on antioxidant enzyme activities, oxidized-LDL level and aortic microscopic changes in rats

Abstract

Organophosphates (OP) are hydrolysed by paraoxonase (PON1), an antioxidant enzyme which has been recognized to inhibit atherosclerosis event by deterring oxidative modification of low density lipoprotein (LDL). Low PON1 activities have been observed among individuals chronically exposed to OP while decreased activities were reported in individuals with higher risk of coronary artery disease (CAD). However, the relationship between chronic OP exposure, PON1 and the development of atherosclerosis has not yet been established. The aims of this study were to investigate the effects of chronic OP exposure on oxidative stress markers and to assess the aorta for atherosclerosis changes in animal model chronically and intermittently exposed to low dose OP. This study involved 20 male Sprague-Dawley rats, were divided into 3 groups; the first group did not receive any injection, while both Group 2 and Group 3 received subcutaneous injection of vehicle and injection of 18.0 mg/kg of chlorpyrifos (CPF) respectively every other day for 180 days. Blood were analysed for PON1 activities and oxidized LDL (ox-LDL), hearts were homogenized for superoxide dismutase (SOD) and catalase (CAT), and aorta were harvested and processed for microscopic examination. The PON1 activities, ox-LDL level and PON1:ox-LDL ratio were found to be significantly lower in OP exposed rats but the intracellular antioxidant enzyme activities were insignificant. Microscopically, the OP exposed rats showed early atherosclerosis changes with positive VCAM-1 expression. In conclusion, chronic intermittent low dose of OP CPF induced the development of early stage of atherosclerosis and this could be due to the inability of the PON1 to hydrolyse ox-LDL.