title: Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress, following administration of pyridostigmine bromide, DEET (N,N-diethyl-m-toluamide) and permethrin, alone and in combination in rats.
abstract: In this study, we determined levels of 3-nitrotyrosine in rat urine following administration of a single oral dose of 13 mg/kg pyridostigmine bromide (PB) (3-dimethylaminocarbonyloxy-N-methylpyridinum bromide), a single dermal dose of 400 mg/kg N,N-diethyl-m-toluamide (DEET) and a single dermal dose of 1.3 mg/kg permethrin, alone and in combination. Urine samples were collected from five treated and five control rats at 4, 8, 16, 24, 48, and 72 h following dosing. Solid-phase extraction coupled with high-performance liquid chromatography with ultraviolet detection at 274 nm was used for the determination of tyrosine and 3-nitrotyrosine. A single oral dose of PB and a single dermal dose of DEET or their combination significantly (P<0.05) increased levels of 3-nitrotyrosine starting 24 h after dosing compared with control urine samples. The maximum increase of 3-nitroytyrosine was detected 48 h after combined administration of PB and DEET. The ratio of 3-nitrotyrosine to tyrosine in urine excreted 48 h after dosing was 0.19+/-0.04, 0.20+/-0.05, 0.28+/-0.03, 0.32+/-0.04, 0.19+/-0.05, 0.42+/-0.04, 0.27+/-0.03, 0.36+/-0.04, and 0.48+/-0.04 following administration of water, ethanol, PB, DEET, permethrin, PB+DEET, PB+permethrin, DEET+permethrin, and PB+DEET+permethrin, respectively. The results indicate that an oral dose of PB and a dermal administration of DEET, alone and in combination, could generate free radical species, and thus increase levels of 3-nitrotyrosine in rat urine. Induction of 3-nitrotyrosine, a marker of oxidative stress, following exposure to these compounds could be significant in understanding the proposed enhanced toxicity following combined exposure to these compounds.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Abu-Qare
authors.forename: H B
authors.initials: HB
authors.lastname: Suliman
authors.forename: M B
authors.initials: MB
authors.lastname: Abou-Donia
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003671:DEET / Q000633:toxicity*; D004347:Drug Interactions; D007302:Insect Repellents / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008889:Military Personnel; D015394:Molecular Structure; D016273:Occupational Exposure; D018384:Oxidative Stress; D026023:Permethrin; D011722:Pyrethrins / Q000633:toxicity*; D011729:Pyridostigmine Bromide / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000652:urine*
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D007302:Insect Repellents; D007306:Insecticides; D011722:Pyrethrins; D003671:DEET; C002744:3-nitrotyrosine; D014443:Tyrosine; D026023:Permethrin; D011729:Pyridostigmine Bromide