Activation of p38MAPK and NRF2 signaling pathways in the toxicity induced by chlorpyrifos in Drosophila melanogaster: Protective effects of Psidium guajava pomífera L. (Myrtaceae) hydroalcoholic extract

Abstract

Chlorpyrifos (CP) is an organophosphate insecticide widely used in the control of agriculture and domestic pests. Occupational exposure is a major form of human poisoning by organophosphates and current therapies for these compounds are not completely efficient. Psidium guajava is a plant widely used in folk medicine and its antioxidant activity has been described. In this study we evaluated the antioxidant and protective potential of the hydroalcoholic extract of P. guajava (HEPG) against CP induced toxicity in the fruit fly Drosophila melanogaster. HEPG in vitro antioxidant activity was confirmed by ABTS, DPPH, Total Phenolics and FRAP assays. The exposure of flies to CP caused increased mortality, locomotor deficits and inhibition of acetylcholinesterase. Flies exposed to CP presented elevated ROS and lipid peroxidation which was accompanied by a significant decrease in mitochondrial viability. As a response to increased oxidative stress, CP exposed flies showed increased GST activity and GSH levels. The mRNA expression of NRF2 and MPK2 (which encodes D. melanogaster p38MAPK) was also significantly up-regulated. HEPG was able to restore all the damage and biochemical/molecular alterations caused by CP. Our results show for the first time the P. guajava potential protective effect against the toxicity caused by chlorpyrifos. Keywords: Organophosphate compound, Oxidative stress, Natural compounds, Protective effects