Cinoxacin のラット生殖に及ぼす影響

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タイトル別名
  • REPRODUCTION STUDIES OF CINOXACIN IN RATS
  • Cinoxacin ノ ラット セイショク ニ オヨボス エイキョウ

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Reproduction studies (i. e. fertility study, teratological study, and perinatal and postnatal study) on cinoxacin (CINX), a new synthetic chemotherapeutic, were carried out in Sic: SD rats.<BR>1) Fertility study<BR>CINX was orally administered once daily at the doses of 50, 100 and 200mg/kg as a suspension in 5% acacia solution. The compound was administered to male rats for 9 weeks and to female rats for 2 weeks prior to mating. The treatment was continued to either sexes during cohabitation period and in females during early pregnancy until day 7 of gestation. All pregnant females were sacrificed on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. Hematuria and crystalluria were sporadically observed in males and females given 100 or 200mg/kg/day of the compound. Renal and uretal injuries accompanying with the enlarged pelvis, increased renal weight and enlarged ureter were also observed in either male or female rats. Mortality was in 6/30 males given 200mg/kg/day, in 1/20 females given 100mg/kg/day and in 9/30 females given 200mg/kg/day of CINX. Growth inhibition, decrease in food consumption and increase in water intake were observed in males and females given 200 mg/kg/day and in females given 100 mg/kg/day of the compound. CINX, however, did not affect the reproductive performances of both sexes and fetal parameters such as growth, development, viability were normal. No abnormalities were observed in visceral and skeletal specimens of the fetuses.<BR>2) Teratological study<BR>CINX was orally administered to pregnant rats once daily for 11 days from day 7 to day 17 of gestation at the doses of 50, 100, 200 and 300mg/kg/day as a suspension in 5% acacia solution and the effect was compared to that of nalidixic acid (NA), the dose of which was 300mg/kg/day. About 2/3 of pregnant rats in each group were sacrificed on day 20 of gestation to examine their fetuses and the remaining dams were allowed to deliver and nurse their young until weaning. Young were examined their viability, growth, behavioral and emotional development and reproductive performances. Clinical symptoms and renal injury of the dams given CINX were similar to those observed in fertility study. Mortality was in 6/30 dams given 200mg/kg/day and in 15/30 dams given 300mg/kg/day of CINX. In the rats given NA, no toxic signs were observed and all dams survived until autopsy. Fetal growth was inhibited in the groups given 200 and 300mg/kg /day of CINX and NA but no gross, visceral and skeletal abnormalities were observed in all the fetuses of CINX group. In NA group, however, the incidence of external defects (cleft palate, systemic edema) and skeletal change (lumbar ribs) increased significantly. The administration of CINX neither affected the parturition and nursing ability of dams, nor were there any adverse effects on growth, viability, behavioral and emotional parameters, and reproductive performances of young. In NA group, survival rate within 4 days after delivery decreased markedly.<BR>3) Perinatal and postnatal study<BR>CINX was orally administered to pregnant rats once daily from day 17 of gestation through postpartum day 21 at the doses of 50, 100 and 200mg/kg/day as a suspension in 5% acacia solution. All pregnant females were allowed to deliver and nurse their young. The young were tested for their growth, viability, fertility, and reproductive performances by obtaining their pups. Clinical symptoms and renal injury of the dams given CINX were similar to those observed in fertility study. Maternal death was observed in 3 during late pregnancy and in 2 at the parturition in the group given 200mg/kg/day of CINX.

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