Collaborative work on evaluation of ovarian toxicity 6) Two- or four-week repeated-dose studies and fertility study of cisplatin in female rats
| Autor: | Takayuki Matsuno, Yusuke Nozaki, Takahiro Sanzen, Rie Fukui, T. Kozaki, Eiko Furubo, Kazuo Kizawa |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Societies Scientific medicine.medical_specialty media_common.quotation_subject Longevity Physiology Antineoplastic Agents Apoptosis Fertility Ovary Motor Activity Biology Toxicology Public-Private Sector Partnerships Drug Administration Schedule Rats Sprague-Dawley Eating Follicle Japan Ovarian Follicle Pregnancy Internal medicine Copulation Toxicity Tests medicine Animals Embryo Implantation media_common Cisplatin Body Weight Uterus Organ Size Embryo Mammalian medicine.disease Rats Endocrinology medicine.anatomical_structure Atresia Vagina Toxicity Gestation Female Corpus luteum Injections Intraperitoneal medicine.drug |
| Zdroj: | The Journal of Toxicological Sciences. 34:S73-S81 |
| ISSN: | 1880-3989 0388-1350 |
| DOI: | 10.2131/jts.34.s73 |
| Popis: | The main aim of the present study is to determine the optimal administration period of cisplatin with regards to its toxic effects on ovarian morphology in the repeated-dose toxicity study. Cisplatin was administered to female SD rats intraperitoneally once daily at dose levels of 0.25, 0.5, 1.0 and 2.0 mg/kg for 2 weeks, or at dose levels of 0.125, 0.25 and 0.5 mg/kg for 4 weeks in the repeated-dose toxicity study. In the female fertility study, 0.25, 0.5 and 1.0 mg/kg of cisplatin were administered in the same manner from 14 days prior to mating to Day 7 of gestation. In the repeated-dose toxicity study, a decrease in large follicle, an increase in atresia of medium and large follicles, and/or a decrease in currently formed corpus luteum were observed in animals receiving 1.0 and 2.0 mg/kg for 2 weeks, and decreases in small and/or large follicles and an increase in atresia of large follicle were observed in animals receiving 0.25 and 0.5 mg/kg for 4 weeks on the histopathological examination of the ovaries. In the female fertility study, the copulation and fertility indices in the animals receiving 1.0 mg/kg tended to be lower than those in the control animals. In conclusion, histopathological changes in the ovary that were attributable to cisplatin dosing were detected by detailed observation of the ovary in the 2-week study; and therefore, a 2-week administration period is sufficient to evaluate the ovarian toxicity of cisplatin. |
| Databáze: | OpenAIRE |
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