Malathion-Induced Impairment of Glucose-Stimulated Insulin Secretion Via Stress Oxidative Process in Isolated Rat Pancreatic Islets: In Vivo And in Vitro Studies

Objective: Malathion is one of the most commonly used organophosphate insecticides (OPs) of the world responsible for impairment of glucose homeostasis. The aim of this surveywas to investigate the relationship between acute exposure to Malathion with oxidative stress elements and functions of pancreatic islets in vitro and in vivo Methods: Pilot study showed that oral administration of Malathion (400 mg/kg) impairs glucose homeostasis after 24 h in wistar rats. Therefore, after 24 h of oral Malathion exposure (400 mg/kg), function of pancreas in response to changes in serum glucose (after oral administration of 2 g/kg glucose) were evaluated using glucose oxidase kit in a time-course fashion (0, 30, 60, 120 and 180 min). The response of the isolated islets to gradient glucose concentrations (2.8, 8.3, 16.7 and 22 mM) was also assessed using insulin ELAISA kit. In addition, the level of cellular lipid peroxidation (fluorometeric method),protein electrophotometric method) and DNA damage were tested using 8-hydroxyguanosine ELASA kit Results: according to time-course study and calculation of insulin/glucose AUC, Malathion decreased insulin response to serum glucose changes in vivo. Static experiments in vitro indicated an impairment of islets insulin secretion in response to glucose concentration gradient. Malathion increased lipid peroxidation and induced protein and DNA damage as confirmed by increase in islets lipid peroxides carbonyl groups, and 8-hydroxyguanosine Conclusion: There is a correlation between rat pancreas and isolated islets response to glucose concentration changes and cellular oxidative stress following acute in vivo and in vitro Malathion exposur