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Evaluation of ovarian toxicity of sodium valproate (VPA) using cultured rat ovarian follicles.
MedLine Citation:
PMID:  22687998     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Sodium valproate (VPA) is a major antiepileptic drug that is widely used for the treatment of epilepsy as well as other neuropsychiatric diseases. The present study was conducted to evaluate the ovarian toxicity of VPA using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with VPA (0, 0.2, 1.0, and 5.0 mM). At 0, 24, and 48 hr of VPA treatment, follicular diameters were measured. After the culture, viability of follicles and expression of aromatase in the follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At all concentrations of VPA, follicular development was suppressed, and androstenedione, testosterone, estradiol, and combined levels of all steroid hormones tended to decrease in association with suppression of aromatase expression in granulosa cells. Additionally, the suppression of follicular development was associated with decreased viability of follicles and an increased progesterone level at 5.0 mM of VPA. The decrease in the combined levels of all steroid hormones implies that VPA suppresses the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. In conclusion, VPA induces ovarian toxicity via suppression of development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.
Authors:
Hiroshi Inada; Kazuhiro Chihara; Akihito Yamashita; Izuru Miyawaki; Chiharu Fukuda; Yumi Tateishi; Takeshi Kunimatsu; Juki Kimura; Hitoshi Funabashi; Takashi Miyano
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of toxicological sciences     Volume:  37     ISSN:  1880-3989     ISO Abbreviation:  J Toxicol Sci     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7805798     Medline TA:  J Toxicol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  587-94     Citation Subset:  IM    
Affiliation:
Safety Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd.
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