Antioxidant response and neurotransmitter modulation driven by oleuropein/alpha-lipoic acid attenuates lead-induced reproductive toxicity and neurotoxicity in Drosophila melanogaster

Abstract

Lead is a ubiquitous environmental and industrial toxicant known to cause reproductive toxicity and neurotoxicity via the induction of oxidative damage and modulation of neurotransmitters. On the other hand, oleuropein and alpha-lipoic acid have independently been reported to demonstrate antioxidant and neurotransmitter modulatory activities. Here, we evaluated the protective role of oleuropein/alpha lipoic acid in lead-induced reproductive toxicity and neurotoxicity in Drosophila melanogaster . A 7-day survival analysis was carried out, and subsequently, flies were exposed to vehicle, lead acetate (20 mg/kg diet), and/or oleuropein and alpha lipoic acid (0.1 mg/kg diet) for 7 days. Oleuropein and alpha lipoic acid restored lead-induced weight loss and suppression of reduced glutathione, superoxide dismutase, and catalase activities, as well as elevated malondialdehyde contents. In addition, oleuropein and alpha lipoic acid ameliorated lead-induced increases in acetylcholinesterase and monoamine oxidase activities and reductions in acetylcholine, dopamine, and serotonin in flies. Additionally, lead-induced disruption of climbing activity, courtship and mating latencies, mating duration, copulation success rate, and emergence rate were ameliorated by oleuropein and alpha lipoic acid in D. melanogaster . Overall, oleuropein and alpha lipoic acid attenuated lead-induced reproductive toxicity and neurotoxicity in D. melanogaster . Thus, oleuropein/alpha lipoic acid is a promising candidate for further investigation against lead-induced toxicity.