Yadav Sanjay, Johri Ashu, Dhawan Alok, Seth Prahlad K, Parmar Devendra
Developmental Toxicology Division, Industrial Toxicology Research Centre, PO Box 80, Mahatma Gandhi Marg, Lucknow-226 001, UP, India.
Toxicol Appl Pharmacol. 2006 Nov 15;217(1):15-24. doi: 10.1016/j.taap.2006.07.008. Epub 2006 Jul 29.
Oral administration of deltamethrin (5 mg/kg x7 or 15 or 21 days) was found to produce a time-dependent increase in the mRNA expression of xenobiotic metabolizing cytochrome P450 1A1 (CYP1A1), 1A2 and CYP2B1, 2B2 isoenzymes in rat brain. RT-PCR studies further showed that increase in the mRNA expression of these CYP isoenzymes observed after 21 days of exposure was region specific. Hippocampus exhibited maximum increase in the mRNA expression of CYP1A1, which was followed by pons-medulla, cerebellum and hypothalamus. The mRNA expression of CYP2B1 also exhibited maximum increase in the hypothalamus and hippocampus followed by almost similar increase in midbrain and cerebellum. In contrast, mRNA expression of CYP1A2 and CYP2B2, the constitutive isoenzymes exhibited relatively higher increase in pons-medulla, cerebellum and frontal cortex. Immunoblotting studies carried out with polyclonal antibody raised against rat liver CYP1A1/1A2 or CYP2B1/2B2 isoenzymes also showed increase in immunoreactivity comigrating with CYP1A1/1A2 or 2B1/2B2 in the microsomal fractions isolated from hippocampus, hypothalamus and cerebellum of rat treated with deltamethrin. Though the exact relationship of the xenobiotic metabolizing CYPs with the physiological function of the brain is yet to be clearly understood, the increase in the mRNA expression of the CYPs in the brain regions that regulate specific brain functions affected by deltamethrin have further indicated that modulation of these CYPs could be associated with the various endogenous functions of the brain.
研究发现，经口给予大鼠溴氰菊酯（5毫克/千克，连续7、15或21天）会使大鼠脑中参与外源性物质代谢的细胞色素P450 1A1（CYP1A1）、1A2以及CYP2B1、2B2同工酶的mRNA表达呈时间依赖性增加。逆转录聚合酶链反应（RT-PCR）研究进一步表明，暴露21天后观察到的这些CYP同工酶mRNA表达增加具有区域特异性。海马体中CYP1A1的mRNA表达增加最为显著，其次是脑桥-延髓、小脑和下丘脑。CYP2B1的mRNA表达在下丘脑和海马体中也增加最为显著，其次是中脑和小脑，增加幅度相近。相比之下，组成型同工酶CYP1A2和CYP2B2的mRNA表达在脑桥-延髓、小脑和额叶皮质中增加相对较多。用针对大鼠肝脏CYP1A1/1A2或CYP2B1/2B2同工酶制备的多克隆抗体进行的免疫印迹研究也显示，从经溴氰菊酯处理的大鼠海马体、下丘脑和小脑中分离的微粒体组分中，与CYP1A1/1A2或2B1/2B2共迁移的免疫反应性增加。虽然参与外源性物质代谢的细胞色素P450与大脑生理功能的确切关系尚待明确，但在受溴氰菊酯影响的调节特定脑功能的脑区中，细胞色素P450的mRNA表达增加进一步表明，这些细胞色素P450的调节可能与大脑的各种内源性功能有关。
