Developmental Toxicology Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow-226001, UP, India; Department of Biochemistry, University of Lucknow, Lucknow-226007, UP, India.
Environ Toxicol Pharmacol. 1999 Jul;7(3):169-78. doi: 10.1016/s1382-6689(99)00011-3.
Deltamethrin, an α-cyano type II pyrethroid, administered orally (5, 10 and 15 mg/kg body weight for 7 consecutive days or at 5 mg/kg for further 15 and 21 days) to young albino Wistar rats (approximately 8 weeks old) produced a dose- and time-dependent increase in the activity of cytochrome P450-dependent 7-ethoxyresorufin-O-dealkylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) in rat liver and brain. However, significant induction in the enzyme activities was observed at higher doses or prolonged exposure. The magnitude of induction in rat liver microsomes was less at 15 mg/kg dose as compared to 10 mg/kg dose. Western blot analysis revealed a similar dose-related and time-dependent increase in the expression of P450 2B1/2B2 and 1A1 isoenzymes as indicated by the increased cross-reactivity of liver microsomes isolated from deltamethrin-treated animals with anti-P450 2B1/2B2 and 1A1. Inhibition of EROD and PROD observed after in vitro addition of anti-P450 2B1/2B2 and 1A1/1A2 or organic inhibitors, metyrapone and α-naphthoflavone, to the brain and liver microsomes of deltamethrin-pretreated animals (5 mg/kg×21 days), further provided support that the induction observed in the EROD and PROD activity in brain is due to the increased expression of P450 2B1/2B2 and 1A1/1A2, while, in the liver, isoenzymes other than these are also involved.
溴氰菊酯，一种 α-氰基 II 型拟除虫菊酯，经口给予（5、10 和 15mg/kg 体重，连续 7 天，或 5mg/kg 体重，进一步给予 15 和 21 天）给年轻白化 Wistar 大鼠（约 8 周龄），导致肝和脑中细胞色素 P450 依赖性 7-乙氧基试卤灵-O-去烷基酶（EROD）和 7-戊氧基试卤灵-O-去烷基酶（PROD）的活性呈剂量和时间依赖性增加。然而，在较高剂量或延长暴露时观察到显著的诱导。与 10mg/kg 剂量相比，15mg/kg 剂量时肝微粒体中酶活性的诱导程度较小。Western blot 分析显示，P450 2B1/2B2 和 1A1 同工酶的表达也呈类似的剂量相关和时间依赖性增加，这表明从溴氰菊酯处理动物中分离的肝微粒体与抗 P450 2B1/2B2 和 1A1 的交叉反应性增加。在体外向溴氰菊酯预处理动物（5mg/kg×21 天）的脑和肝微粒体中添加抗 P450 2B1/2B2 和 1A1/1A2 或有机抑制剂甲吡酮和 α-萘黄酮后观察到 EROD 和 PROD 的抑制作用，进一步支持了在 EROD 和 PROD 活性中观察到的诱导作用是由于 P450 2B1/2B2 和 1A1/1A2 的表达增加所致，而在肝脏中，除这些以外的同工酶也参与其中。
