The oxidative damage and inflammation caused by pesticides are reverted by lipoic acid in rat brain

Abstract

We have previously demonstrated that the administration of low doses of dimethoate, glyphosate and zineb to rats (i.p. 1/250 LD50, three times a week for 5 weeks) provokes severe oxidative stress (OS) in specific brain regions: substantia nigra, cortex and hippocampus. These effects were also observed in plasma. Lipoic acid (LA) is considered an ‘‘ideal antioxidant’’ due to its ability to scavenge reactive species, reset antioxidant levels and cross the blood–brain barrier. To investigate its protective effect we administered LA (i.p. 25, 50 and 100 mg/kg) simultaneously with the pesticide mixture (PM) for 5 weeks. After suppression of PM administration, we evaluated the restorative effect of LA for a further 5 weeks. LA prevented OS and the production of nitrites + nitrates [NOx] caused by PM in a dose-dependent manner. The PM-induced decrease in reduced glutathione and a-tocopherol levels in all brain regions was completely restored by LA at both high doses. PM administration also caused an increase in prostaglandins E2 and F2a in brain that was reduced by LA in a dose-dependent fashion. Taking into account the relationship between OS, inflammation and apoptosis, we measured caspase and calpain activity. Only milli- and micro-calpain isoforms were increased in the PM-treated group and LA reduced the activities to basal levels. We also demonstrated that interrupting PM administration is not enough to restore the levels of all the parameters measured and that LA is necessary to achieve basal status. In our experimental model LA displayed a protective role against pesticide-induced damage, suggesting that LA administration is a promising therapeutic strategy to cope with disorders suspected to be caused by OS generators, especially in brain.