Liver δ-aminolevulinate dehydratase activity is inhibited by neonicotinoids and restored by antioxidant agents.
Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D), protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (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 chemical elements found in the constitution of pesticides. Reduced glutathione (GSH) had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA), in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids.
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. elisa-sauer@hotmail.com.
Elisa
E
Sauer
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. angelammoro@yahoo.com.br.
Angela M
AM
Moro
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. nataliafarma@hotmail.com.
Natália
N
Brucker
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. sabrinascimento@hotmail.com.
Sabrina
S
Nascimento
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. bruna_gauer@hotmail.com.
Bruna
B
Gauer
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. rafael.fra@hotmail.com.
Rafael
R
Fracasso
Department of Chemistry, Pontiﬁcal Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ 22453900, Brazil. agioda@hotmail.com.
Adriana
A
Gioda
Department of Production and Drug Control, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. ruy.beck@ufrgs.br.
Ruy
R
Beck
Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035003, Brazil. 00006866@ufrgs.br.
José C F
JC
Moreira
Department of Production of Source-Material, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. veraeifler@ufrgs.br.
Vera Lucia
VL
Eifler-Lima
Laboratory of Toxicology (LATOX), Department of Clinical and Toxicology Analysis, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil. solange.garcia@ufrgs.br.
Solange Cristina
SC
Garcia
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D007093:Imidazoles / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; C082359:imidacloprid; D000623:Porphobilinogen Synthase