Cytotoxicity induced by deltamethrin and its metabolites in SH-SY5Y cells can be differentially prevented by selected antioxidants

Deltamethrin, an α-cyano pyrethroid insecticide, is a relatively potent neurotoxicant. The main deltamethrin metabolism mechanisms are ester cleavage and oxidation at the 2′ and 4′ position of the terminal aromatic ring. Although some aspects of the toxicity properties of deltamethrin have been reported, limited information is available about the metabolites cytotoxic actions. The aims of this study are to examine in vitro neurotoxicity of deltamethrin and its metabolites 3-phenoxybenzoic acid (3-PBA), 2′-OH-deltamethrin, and 4′-OH-deltamethrin and to evaluate melatonin (0.1, 1 μM), trolox (0.3, 1 μM) and N-acetylcysteine (500, 1000 μM) protective role in SH-SY5Y cells. MTT and neutral red uptake (NRU) assays were carried out to assess the cytotoxicity of deltamethrin and its metabolites. Of the three metabolites tested, while 3-PBA (0.01-1000 μM) did not show neurotoxicity, 2′-OH- and 4′-OH-deltamethrin (10-1000 μM) were more toxic than deltamethrin (10-1000 μM). Levels of both nitric oxide (NO) and lipid peroxides measured as malondialdehyde were significantly increased in deltamethrin and 4′-OH-deltamethrin-treated cells. Compared to other antioxidants, 1 μM MEL treatment effectively protected against deltamethrin and 4′-OH-deltamethrin-induced lipid peroxidation and ameliorated the NO adverse effect that might have been caused. These results suggest that oxidative stress observed is one of the major mechanisms of deltamethrin-induced neurotoxicity and it may be attributed in part to deltamethrin disposition and metabolism.

► Cytotoxicity of deltamethrin and its metabolites were investigated. ► Metabolites 2′ and 4′-OH-deltamethrin are more cytotoxic than deltamethrin. ► The main mechanism of action of these compounds seems to be through oxidative stress. ► Melatonin protects against oxidative stress and lipid peroxidation induced by deltamethrin and its metabolites.