title: Indole-3-carbinol alters placental cytochrome P450 1A1 and P-glycoprotein levels in rats: a potential role in intensifying fetal intrauterine growth-retardation produced by tobacco smoke.
abstract: To investigate the deleterious effects and possible mechanism of prenatal indole-3-carbinol (I3C) treatment on normal and tobacco-induced intrauterine growth restriction (IUGR) in rats, prenatal development toxicity in rats was studied. Expression of rat placental cytochrome P4501A1 (CYP1A1) and P-glycoprotein (Pgp), including mdr1a and mdr1b, were detected using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Results showed that prenatal oral I3C had no significant effects on corpora lutea counts, implantation or the number of live, dead and resorbed fetuses in normal rats. Fetal malformations, sex ratio, neonatal body weights and physical developmental indices were also unchanged after prenatal I3C treatment. However, the offspring in the tobacco + I3C (4 mg kg(-1)) group showed lower average body weights (3.98+/-0.29 g) than tobacco control (4.48+/-0.11 g), and body and tail lengths lagged significantly behind those of the tobacco-smoke exposure only group. Expression of placental CYP1A1 mRNA by RT-PCR was not detected in the normal group, but was detected in the I3C, tobacco and tobacco + I3C groups. The level of CYP1A1 mRNA expression in the tobacco + I3C group was higher than in tobacco control. The level of mdr1a mRNA increased significantly in the I3C group when compared to normal control, and no obvious difference was detected between tobacco and tobacco + I3C groups. Expression of mdr1b mRNA was increased in the I3C and tobacco + I3C groups compared to their respective controls. Immunohistochemistry results showed that placental Pgp expression was enhanced in the I3C, tobacco and tobacco + I3C groups when compared to the normal control. The results suggest that prenatal oral I3C had no developmental toxicity but intensified fetal IUGR produced by prenatal tobacco-smoke exposure in rats. Up-regulations of placental CYP1A1 and Pgp by I3C might underlie the toxic mechanism.
authors.affiliation: Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan 430071, China.
authors.forename: You-E
authors.initials: YE
authors.lastname: Yan
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Han-Gao
authors.initials: HG
authors.lastname: Zeng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007211:Indoles / Q000633:toxicity*; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects; D013047:Specific Pathogen-Free Organisms; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007211:Indoles; D012333:RNA, Messenger; D012906:Smoke; D014028:Tobacco Smoke Pollution; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1