1. Collaborative work on evaluation of ovarian toxicity 15) Two- or four-week repeated-dose studies and fertility study of bromocriptine in female rats
- Author
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Zhu Jiuxin, Satoko Harada, Yoshiaki Tagawa, Toshihiko Kumazawa, Hiromi Nishitani, Tsukasa Ishiguro, Takashi Tanaharu, Yukiko Inoue, Ikuo Hayasaka, and Atsushi Nakajima
- Subjects
Male ,Societies, Scientific ,medicine.medical_specialty ,Longevity ,Fertility Study ,Estrous Cycle ,Ovary ,Toxicology ,Public-Private Sector Partnerships ,Drug Administration Schedule ,Bromocriptine Mesylate ,Antiparkinson Agents ,Rats, Sprague-Dawley ,Japan ,Corpus Luteum ,Pregnancy ,Proliferating Cell Nuclear Antigen ,Internal medicine ,Toxicity Tests ,medicine ,Animals ,Ovarian Diseases ,Adverse effect ,Bromocriptine ,Estrous cycle ,business.industry ,Organ Size ,Rats ,Fertility ,medicine.anatomical_structure ,Endocrinology ,Pituitary Gland ,Toxicity ,Gestation ,Female ,business ,Infertility, Female ,medicine.drug - Abstract
The main focus of this study is to determine the optimal administration period concerning toxic effects on ovarian morphological changes in a repeated-dose toxicity study. To assess morphological and functional changes induced in the ovary by bromocriptine, the compound was administered to female rats at dose levels of 0, 0.08, 0.4 and 2 mg/kg for the 2- or 4-week repeated-dose toxicity study, and for the female fertility study from 2 weeks prior to mating to day 7 of gestation. In the 2-week repeated-dose toxicity study, increase of ovarian weights was observed at 2 mg/kg. In the 4-week repeated-dose toxicity study, ovarian weights were increased at 0.4 and 2 mg/kg. The number of corpora luteum was increased in the 0.4 and 2 mg/kg groups of the 2- and 4-week repeated-dose toxicity studies by histopathological examination of the ovaries. Bromocriptine did not affect estrous cyclicity in 2- and 4-week repeated dosing. In the female fertility study, although animals in any groups mated successfully, no females in 0.4 and 2 mg/kg groups were pregnant. There were no adverse effects on reproductive performance in the 0.08 mg/kg group. Based on these findings, the histopathological changes in the ovary are considered important parameters for evaluation of drugs including ovarian damage. We conclude that a 2-week administration period is sufficient to detect ovarian toxicity of bromocriptine in a repeated-dose toxicity study.
- Published
- 2009