Annual Meeting of the Japanese Society of Toxicology
32nd Annual Meeting of the Japanese Society of Toxicology
Session ID : Y-24
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Outstanding Researcher Award
Recovery from pregnancy-induced down-regulation of cytochrome P450 isozymes (CYPs) protein levels in postpartum rat liver
*XI JUN HENORIKO EJIRIHIROYUKI NAKAYAMAKUNIO DOI
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Abstract
Although CYP expression which is involved in drug metabolism has been suggested to be influenced by some physiological status, such as pregnancy and lactation, the details remain poorly known. In the present study, the alterations of CYPs expression during pregnancy and postpartum in the F344 rat liver were investigated by Western blot analysis and immunostain. Total nine anti-rat CYPs antibodies (CYP1A1, CYP2B1/2, CYP2C6, CYP2C12, CYP2D1, CYP2D4, CYP2E1, CYP3A1, and CYP4A1) were used. In comparison with age-matched non-pregnant control rats, there were significant decreases in hepatic levels of CYP2B2, CYP2C6 and CYP4A1 in mid-pregnancy (day 13) and CYP2B2, CYP2C6, CYP4A1, CYP1A1, CYP2B1 and CYP2E1 in late-pregnancy (day 19). By postpartum 28 day (PPD 28), however, the hepatic CYPs down-regulated during pregnancy reverted to the same level of control rats. The expression of CYP2C12, CYP2D1 and CYP3A1 remained unchanged even by pregnancy. CYP2D4 was not detectable in all the liver samples examined. The results of immunostain revealed that CYP1A1 was expressed in endothelial cells of both sinusoids and veins in the liver. The other CYPs were mainly expressed in centrilobular hepatocytes. There were no differences in the distribution and intensity of the expression of the CYPs between pregnant and non-pregnant rats. These results provide the possibility that pregnant and lactational animals are more susceptible to some toxic substrates which are metabolized by CYPs.
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© 2005 The Japanese Society of Toxicology
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