Japanese Journal of Veterinary Research;Volume 47, Number 1-2

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Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats

KHLOOD, El. Bohi M.;MIYOSHI, Hiroyuki;IWATA, Hisato;KAZUSAKA, Akio;KON, Yasuhiro;ABOU HADID, ALi H.;MOUSTAFE, El. Kelish;GHONIM, Mervat H.;FUJITA, Shoichi

Permalink : http://hdl.handle.net/2115/2725
JaLCDOI : 10.14943/jjvr.47.1-2.13
KEYWORDS : All-trans-retinoic acid (RA);Cytochrome P-450.;Drug metabolism.;Fetal malformation.;3-Methylcholanthrene (3-MC)

Abstract

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects : the fetal resorption amounted to~60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severeness of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.

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