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, 1μM), trolox (0.3, 1μM) and N-acetylcysteine (500, 1000μM) 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 (0.01-1000μM) did not show neurotoxicity, 2'-OH- and 4'-OH-deltamethrin (10-1000μM) were more toxic than deltamethrin (10-1000μM). 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, 1μM 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.
Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain. aromero@vet.ucm.es
Alejandro
A
Romero
Eva
E
Ramos
Víctor
V
Castellano
María Aranzazu
MA
Martínez
Irma
I
Ares
Marta
M
Martínez
María Rosa
MR
Martínez-Larrañaga
Arturo
A
Anadón
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001565:Benzoates / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology; D009499:Neutral Red / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism / Q000633:toxicity*; D009573:Nitrites / Q000378:metabolism; D011722:Pyrethrins / Q000378:metabolism / Q000633:toxicity*
D000975:Antioxidants; D001565:Benzoates; D002839:Chromans; D007306:Insecticides; D009570:Nitriles; D009573:Nitrites; D011722:Pyrethrins; D009499:Neutral Red; C017180:decamethrin; C017618:3-phenoxybenzoic acid; D008550:Melatonin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine