title: A metabonomic investigation of the effects of 60 days exposure of rats to two types of pyrethroid insecticides.
abstract: Type I and II pyrethroid insecticides display different neurotoxicity. To investigate the long-term (60 days exposure) metabolic effect of the two types of pyrethroid insecticides deltamethrin and permethrin, (1)H nuclear magnetic resonance (NMR) spectroscopy-based metabonomics was used to analyze the biochemical composition of urine and serum samples from rats administrated daily with deltamethrin or permethrin for 60 consecutive days, and principal component analysis used to visualize similarities and differences in the resultant biochemical profiles. Rats treated with either deltamethrin or permethrin displayed increased levels of urinary acetate, dimethylamine, dimethylglycine, trimethylamine and serum free amino acids, and decreased urinary 2-oxoglutarate, all of which are indicative of kidney lesions and nephrotoxicity. The reduced excretion of tricarboxylic acid cycle intermediates, together with increased 3-D-hydroxybutyrate, acetate, and lactate in treated rats could suggest disturbance of the energy metabolism, including an increased rate of anaerobic glycolysis, enhanced fatty acid β-oxidation and ketogenesis. These results show that these two types of insecticides have similarities in the urine and serum spectra, indicating that similar metabolic pathways are perturbed by the insecticides, which induced hepatotoxicity and nephrotoxicity. This approach may lead to the discovery of novel biomarkers of pyrethroids toxicity and thereby provide new insights into the toxicological mechanisms of pesticides pyrethroids.
authors.affiliation: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Liang
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Ding-Xin
authors.initials: DX
authors.lastname: Long
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D004334:Drug Administration Schedule; D007306:Insecticides / Q000737:chemistry / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D009570:Nitriles / Q000737:chemistry / Q000633:toxicity*; D026023:Permethrin / Q000737:chemistry / Q000633:toxicity*; D025341:Principal Component Analysis; D011722:Pyrethrins / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D026023:Permethrin
keywords: (1)H NMR; (1)H nuclear magnetic resonance; 2,2′,3,3′-deuterotrimethylsilylpropionic acid; 2-OG; 2-oxoglutarate; 3-D-HB; 3-D-hydroxybutyrate; DMA; DMG; FIDs; LD(50); LDL/VLDL; NMR spectroscopy; PCA; Pyrethroid insecticide; Rat; SIMCA; Serum; TMA; TMAO; TSP; Urine; dimethylamine; dimethylglycine; free induction decays; half-lethal doses; low- and very low- density lipoprotein; principal components analysis; soft independent modeling of class analogy; trimethylamine; trimethylamine-N-oxide