Abu-Qare A W, Suliman H B, Abou-Donia M B
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Toxicol Lett. 2001 Apr 30;121(2):127-34. doi: 10.1016/s0378-4274(01)00330-7.
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.
在本研究中，我们测定了大鼠单次口服13 mg/kg溴吡斯的明（PB，3 - 二甲基氨基甲酰氧基 - N - 甲基吡啶溴化物）、单次经皮给予400 mg/kg N,N - 二乙基 - m - 甲苯胺（DEET）以及单次经皮给予1.3 mg/kg氯菊酯后，单独及联合给药情况下大鼠尿液中3 - 硝基酪氨酸的水平。给药后4、8、16、24、48和72小时，从五只处理组大鼠和五只对照组大鼠收集尿液样本。采用固相萃取结合在274 nm处进行紫外检测的高效液相色谱法测定酪氨酸和3 - 硝基酪氨酸。与对照尿液样本相比，单次口服PB以及单次经皮给予DEET或它们的组合在给药后24小时显著（P<0.05）提高了3 - 硝基酪氨酸的水平。在PB和DEET联合给药后48小时检测到3 - 硝基酪氨酸的最大增幅。给药后48小时排出的尿液中，3 - 硝基酪氨酸与酪氨酸的比值在给予水、乙醇、PB、DEET、氯菊酯、PB + DEET、PB + 氯菊酯、DEET + 氯菊酯以及PB + DEET + 氯菊酯后分别为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和0.48±0.04。结果表明，口服PB以及经皮给予DEET，单独及联合给药，均可产生自由基，从而提高大鼠尿液中3 - 硝基酪氨酸的水平。接触这些化合物后诱导产生的3 - 硝基酪氨酸（氧化应激的标志物）对于理解这些化合物联合接触后所提出的增强毒性可能具有重要意义。
