Regional specificity in deltamethrin induced cytochrome P450 expression in rat brain.
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.
Yadav
Sanjay
S
Developmental Toxicology Division, Industrial Toxicology Research Centre, PO Box 80, Mahatma Gandhi Marg, Lucknow-226 001, UP, India.
Johri
Ashu
A
Dhawan
Alok
A
Seth
Prahlad K
PK
Parmar
Devendra
D
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003580:Cytochromes; D004790:Enzyme Induction / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D003580:Cytochromes; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D012333:RNA, Messenger; C017180:decamethrin; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1