Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer
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- 作者：Shimomura ; Kazuhiro ; Shimada ; Makoto ; Hagiwara ; Miyoko ; Harada ; Shigeo ; Kato ; Michiyuki ; Furuhama ; Kazuhisa
- 关键词：Nefiracetam ; Testicular toxicity ; Semen analyses ; Hormone analyses ; Dog
- 刊名：Reproductive Toxicology
- 出版年：2004
- 出版时间：May, 2004
- 年：2004
- 卷：18
- 期：3
- 页码：423-430
- 全文大小：340 K
文摘
To investigate mechanisms of the testicular toxicity of nefiracetam and to find sensitive parameters to predict the toxicity, male beagle dogs were orally administered 180 or 300mg/kg per day of the drug once and for 1 and 4 weeks. Time-course changes in serum and/or testicular hormone levels and semen parameters, and testicular morphology were examined. The testicular testosterone level was decreased 4h after single administration of nefiracetam at 300mg/kg per day, but the progesterone level showed no change at that time. The serum testosterone level was decreased after single, 1-week or 2-week treatment. In contrast, the serum estradiol level was increased from 1- to 4-week treatment. No changes in serum LH, FSH and inhibin B levels were observed throughout the experimental period. Decreased sperm motility and increased number of malformed sperms were first observed in semen after 4-week treatment. Histopathological examination of the testis revealed moderate and severe seminiferous atrophy with multinucleated giant cell formation at 180 and 300mg/kg per day, respectively, after 4-week treatment, but not 1-week treatment. These results show that nefiracetam decreases testicular testosterone level in dogs following single oral administration of a high dose, and induces severe morphologic changes after 4-week treatment. This reduction is shown to be a sensitive parameter to detect the toxicity, and is suggested to be induced by the impaired conversion of progesterone to testosterone in Leydig cells.