Yan You-E, Wang Hui, Wang Ting, Zeng Han-Gao
Department of Pharmacology, Basic Medical College of Wuhan University, Wuhan 430071, China.
Exp Toxicol Pathol. 2006 Aug;58(1):39-47. doi: 10.1016/j.etp.2006.05.004. Epub 2006 Jun 27.
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.
为研究孕期给予吲哚 - 3 - 甲醇（I3C）对正常及烟草诱导的大鼠宫内生长受限（IUGR）的有害影响及可能机制，对大鼠孕期发育毒性进行了研究。采用逆转录 - 聚合酶链反应（RT - PCR）和免疫组织化学方法检测大鼠胎盘细胞色素P4501A1（CYP1A1）和P - 糖蛋白（Pgp，包括mdr1a和mdr1b）的表达。结果显示，孕期口服I3C对正常大鼠的黄体计数、着床或活胎、死胎及吸收胎数量均无显著影响。孕期I3C处理后，胎儿畸形、性别比例、新生仔鼠体重及身体发育指标也未发生改变。然而，烟草 + I3C（4 mg kg⁻¹）组后代的平均体重（3.98±0.29 g）低于烟草对照组（4.48±0.11 g），其体长和尾长显著落后于仅暴露于烟草烟雾的组。RT - PCR检测显示，正常组未检测到胎盘CYP1A1 mRNA表达，而I3C组、烟草组及烟草 + I3C组均检测到。烟草 + I3C组CYP1A1 mRNA表达水平高于烟草对照组。与正常对照组相比，I3C组mdr1a mRNA水平显著升高，烟草组与烟草 + I3C组之间未检测到明显差异。与各自对照组相比，I3C组和烟草 + I3C组mdr1b mRNA表达增加。免疫组织化学结果显示，与正常对照组相比，I3C组、烟草组及烟草 + I3C组胎盘Pgp表达增强。结果表明，孕期口服I3C无发育毒性，但会加剧孕期烟草烟雾暴露所致的胎儿IUGR。I3C上调胎盘CYP1A 和Pgp可能是其毒性机制。
Zotero 插件