Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine grow

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lixiangzone119
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Aim: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1 Al (CYPlAl) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYPlAl in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats. Methods: An IUGR model was produced by passive tobacco smoking from GD 7 to parturition (GD 21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYPlAl and P-gp (mdr la and mdr lb) were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. Results: Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities of superoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYPlAl mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD 21 but not at GD 14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. Conclusion: The expression of placental CYPlAl and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYPlAl can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism, upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR Aim: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1 Al (CYPlAl) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYPlAl in tobacco smoke-induced Methods: An IUGR model was produced by passive tobacco smoking from GD 7 to parturition (GD 21) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alterations and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYPlAl and P-gp (mdr la and mdr lb) were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. Results: and the malondialdehyde content increased, but the activities of superoxide dismutase and CAT lowered, when compared to their controls. In the rat pl acenta of the tobacco group, the level of CYP1Al mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD 21 but not at GD 14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. Conclusion: The expression of placental CYPlAl and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYPlAl can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism, upregulation of P-gp may decrease tobacco exposure to a developing fetus with IUGR
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