Antioxidant and acetylcholinesterase response to repeated malathion exposure in rat cerebral cortex and hippocampus.

The wide use of the organophosphate insecticide malathion is accompanied by the risk of human exposure, especially in developing countries, which underlines the need of basic studies in this area. Some reports have shown that low doses of malathion, in a repeated treatment regimen, are unable to reduce acetylcholinesterase (AChE) activity in the rat brain, in contrast to the inhibitory effect in acute treatment. In order to investigate if AChE activity is affected by repeated low-level malathion administration, female Wistar rats were exposed to malathion (50 and 100 mg/kg, intraperitoneally) for 3 consecutive days. Exposure to malathion 50 mg/kg did not affect AChE activity, as previously observed. Contrary to expectation, 100 mg/kg malathion produced a significant increase in AChE activity in both cerebral cortex and hippocampus. Besides AChE inhibition, malathion may act as a pro-oxidative agent by interfering with antioxidant defences, as shown by a decrease of glutathione peroxidase and glutathione reductase activity in the cerebral cortex (100 mg/kg malathion). These effects are in contrast to response in the hippocampus where the increase in AChE activity correlates positively with the antioxidant defences, while the opposite was found in the cerebral cortex. These data indicate that, with low doses, and after a short period of exposure, malathion induces an up-regulation of AChE activity, a pattern similar to that found in the hippocampus for the antioxidant defences studied. The cerebral cortex was more vulnerable to malathion, as reflected in a decrease of two antioxidant enzymes. This study indicates that (i) alternatively to AChE inhibition, interference with the antioxidant defence system may be another important target for malathion toxicity; (ii) hippocampal and cortical AChE activity in rats can be increased after repeated low-dose malathion exposure. This response suggests the occurrence of a pathophysiological response in order to maintain the homeostasis of the cholinergic system in these cerebral structures.