Induction of rat brain and liver cytochrome P450 1A1/1A2 and 2B1/2B2 isoenzymes by deltamethrin

Deltamethrin, an alpha-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) pro duced a dose- and time-dependent increase in the activity of cytochrome P45 0-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 dos e as compared to 10 mg/kg dose. Western blot analysis revealed a similar do se-related and time-dependent increase in the expression of P450 2B1/2B2 an d 1A1 isoenzymes as indicated by the increased cross-reactivity of liver mi crosomes isolated from deltamethrin-treated animals with anti-P450 2B1/2B2 and 1A1. Inhibition of EROD and PROD observed after in vitro addition of an ti-P450 2B1/2B2 and 1A1/1A2 or organic inhibitors, metyrapone and alpha-nap hthoflavone, to the brain and liver microsomes of deltamethrin-pretreated a nimals (5 mg/kg x 21 days), further provided support that the induction obs erved in the EROD and PROD activity in brain is due to the increased expres sion of P450 2B1/2B2 and 1A1/1A2, while, in the liver, isoenzymes other tha n these are also involved. (C) 1999 Elsevier Science B.V. All rights reserv ed.