Liver δ aminolevulinate dehydratase activity is inhibited by neonicotinoids and restored by antioxidant agents

Abstract

Currently, the neonicotinoid represent class of insecticides most used worldwide, and its precursor, imidacloprid, the most widely marketed. They are classified as agents of low toxicity, however there are recent reports of neonicotinoid poisoning and studies in vitro and in vivo demonstrate their toxicity as well as potential oxidizing effect. In this line, the aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ ALA-D and the protective effect of potential antioxidants against this potential effect. Furthermore, we investigated the presence of metals in the constitution of this pesticide. We observed that the activity of hepatic δ ALA-D was significantly inhibited in the presence of imidacloprid at all concentrations tested (2, 5, 10, 20 and 40 mM) and this inhibition was dose-dependent. IC50 value obtained was 20.06±0.17 mM and used to evaluate the restoration of the enzymatic activity. This inhibition was completely restored by addition of DTT and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II), which can be explained by the presence of metals found also in the constitution of pesticides, which are probably contributing with the insecticide toxicity. The main endogenous antioxidant GSH (1000M) had the best antioxidant (67%) against to the effect of imidacloprid, followed by curcumin (5M) and resveratrol (5M/10M) (65 % and 61% respectively). Knowing that inhibition of the enzyme δ ALA-D results in accumulation of its substrate neurotoxic δ-ALA, further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and usability of these antioxidants as antidotes for poisoning cases neonicotinoids.