6-Mercaptopurine-induced histopathological changes and xanthine oxidase expression in rat placenta
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- Taki Kenji
- Department of Biochemical Toxicology, School of Pharmacy, Showa University Pfizer Japan Inc., Drug Safety R&D, Pfizer Global R&D
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- Fukushima Tamio
- Department of Biochemical Toxicology, School of Pharmacy, Showa University Shionogi Co, Ltd. Drug Safety Evaluation
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- Ise Ryota
- Department of Biochemical Toxicology, School of Pharmacy, Showa University Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories (SNBL)
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- Horii Ikuo
- Department of Biochemical Toxicology, School of Pharmacy, Showa University Pfizer Japan Inc., Drug Safety R&D, Pfizer Global R&D
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- Yoshida Takemi
- Department of Biochemical Toxicology, School of Pharmacy, Showa University
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抄録
The placenta secures the embryo and fetus to the endometrium and releases a variety of steroid and peptide hormones that convert the physiology of a female to that of a pregnant female. Chemical-induced alteration or deviation of placental function in the maternal and extraembryonic tissue can ultimately lead to pregnancy loss, congenital malformation and fetal death. The 6-mercaptopurine (6-MP), an anti-leukemic drug, is known to produce undesired effects on some organs, then the placenta/embryo toxicity of 6-MP was investigated in pregnant rats given 60 mg/kg with two intraperitoneal injections on gestation days (GD) 11 and 12. The rats were sacrificed and their placentas were collected on GD13 or 15. On GD15 small and limb-defected embryos were found in the 6-MP-treated rats. Placental weights were significantly reduced on GD15, as well as a reduced number of cells was detected in the labyrinth zone with both the labyrinth and basal zones having thinned. Cleaved caspase-3-positive cells increased in number in the labyrinth zone, while in the basal zone, glycogen cells reduced with cytolysis. The number of spongiotrophoblasts and trophoblastic giant cells also increased by 6-MP treatment. The 6-MP-treatment resulted in the increased xanthine oxidase (Xdh) expression in the placenta, which gene is related to the ischemic condition of tissues. These data suggest that apoptosis of the labyrinth zone cells may lead to decreased materno-fetal exchange. Moreover, subsequent ischemia in the placental tissue may occur and induce Xdh expression.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 37 (3), 607-615, 2012
一般社団法人 日本毒性学会
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詳細情報
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- CRID
- 1390282679881036160
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- NII論文ID
- 130004446981
- 10030436433
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC38XhtFajurrF
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 023833102
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- PubMed
- 22688000
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可