The metabolism of imidacloprid by aldehyde oxidase contributes to its clastogenic effect in New Zealand rabbits

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Vardavas, AI (Author) Other; Ozcagli, E (Author) Other; Fragkiadaki, P (Author) Other; Stivaktakis, PD (Author) Other; Tzatzarakis, MN (Author) Other; Alegakis, AK (Author) Other; Vasilaki, F (Author) Other; Kaloudis, K (Author) Other; Tsiaoussis, J (Author) Other; Kouretas, D (Author) Other; Tsitsimpikou, C (Author) Other; Felix Carvalho (Author) FFUP; Tsatsakis, AM (Author) Other

Journal

Title: Mutation Research - Genetic Toxicology and Environmental Mutagenesis

Vol. 829

Pages: 26-32

ISSN: 1383-5718

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00N-SSB

DOI: 10.1016/j.mrgentox.2018.03.002

Abstract (EN): Imidacloprid (IMI) is a systemic, chloro-nicotinyl insecticide classified in Regulation No 1272/2008 of the European Commision as "harmful if swallowed and very toxic to aquatic life, with long-lasting effects". IMI is metabolized in vitro both by aldehyde oxidase (AOX) (reduction) and by cytochrome P450s enzymes (CYPs). In the present study, the AOX inhibitor sodium tungstate dihydrate (ST) was used to elucidate the relative contribution of CYP 450 and AOX metabolic pathways on IMI metabolism, in male rabbits exposed to IMI for two months. To evaluate the inhibition effectiveness, various metabolite concentrations in the IMI and IMI + ST exposed groups were monitored. DNA damage was also evaluated in micronucleus (MN) and single cell electrophoresis (SCGC) assays in both groups, along with oxidative stress (OS) with the inflammatory status of the exposed animals, in order to clarify which metabolic pathway is more detrimental in this experimental setting. A significant increase in the frequency of binucleated cells with MN (BNMN, 105%) and micronuclei (MN, 142%) was observed after exposure to IMI (p < 0.001). The increase in the ST co-exposed animals was less pronounced (BNMN 75%, MN 95%). The Cytokinesis Block Proliferation Index (CBPI) showed no significant difference between controls and exposed animals at any time of exposure (p > 0.05), which indicates no cytotoxic effect. Similarly, comet results show that the IMI group exhibited the highest achieved tail intensity, which reached 70.7% over the control groups, whereas in the IMI + ST groups the increase remained at 48.5%. No differences were observed between all groups for oxidative-stress biomarkers. The results indicate that the AOX metabolic pathway plays a more important role in the systemic toxicity of IMI.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7