Biomedical subjects

K Kuroyanagi

Publications and source records attributed to K Kuroyanagi.

At least 91 records · Page 5Linked to original sources

PubMed1986

[Reproduction studies of VP 16-213 (IV)--Oral administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 1, 3 and 10 mg/kg/day. The summarized results obtained are as follows: VP 10 mg/kg induced thymic atrophy in dams. VP failed to affect the parturition of dams. VP 10 mg/kg lowered the viability of newborns (F1) on postpartum day 3 and increased the days required for descending of testes, but failed to affect the growth of genital organs, learning ability, motility motor activity or emotional development. VP 10 mg/kg brought a transient suppression of body weight increase in pregnant F1 rats, but failed to affect their reproductive ability and parturition. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Long-term rearing F1 rats derived from VP-treated dams manifested no delayed toxicity including carcinogenicity. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 3 mg/kg/day against dams and their offspring.

Administration, Oral↗

PubMed1986

[Reproduction studies of VP 16-213 (V)--Intravenous administration to rats prior to and in the early stages of pregnancy].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to male Crj: CD (Sprague-Dawley) rats for 61 days and to female rats of the same strain for 14 days prior to mating at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summarized results obtained are as follows: Body weight increases were suppressed at the dose level of VP 0.8 mg/kg in males and females. VP 0.2 and 0.8 mg/kg decreased the thymic weight and 0.8 mg/kg decreased testicular and epididymal weight in males showing macroscopic atrophy of these organs, but these doses failed to affect the reproductive ability and so on in parent rats. As for fetuses, VP 0.8 mg/kg elevated the mortality, decreased the number of survivors and suppressed their growth. Furthermore, this dose raised the incidences of anophthalmia, microphthalmia, dilated lateral ventricles and unossified 5th and 6th sternums, as well as brought retarded ossification of sternums, cervical vertebrae, sacral and coccygeal vertebrae, metacarpus and thoracic vertebrae. Based on these results, the no-effect dose levels of VP under the present experimental condition were estimated to be 0.05 mg/kg/day against parent rats of both sexes and 0.2 mg/kg/day against their offspring.

Animals↗

PubMed1986

[Reproduction studies of VP 16-213 (VI)--Intravenous administration to rats during the perinatal and lactation periods].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to female Crj: CD (Sprague-Dawley) rats from day 17 of gestation through postpartum day 20 at dose levels of 0.05, 0.2 and 0.8 mg/kg/day. The summarized results obtained are as follows: VP 0.2 and 0.8 mg/kg suppressed the body weight increase and brought thymic atrophy in dams. VP failed to affect the states of birth of newborns (F1). In F1 offspring, VP 0.8 mg/kg increased the days required for testicular descending and vaginal opening, and suppressed the body weight increase, but failed to affect the growth of genital organs, reproductive ability, learning ability, motility, motor activity or emotional development. F2 newborns derived from F1 rats whose dams had ever received VP during the prenatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of VP under the present experimental condition was estimated to be 0.05 mg/kg/day against dams and 0.2 mg/kg/day against their offspring.

Animals↗

PubMed1986

[Toxicity studies of VP 16-213 (III)--Oral six-month chronic toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 1, 3, 10 and 30 mg/kg/day for six months with the object of examining its chronic toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought transient diarrhea, anemia and depilation. Some animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 3 mg/kg and higher predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 30 mg/kg lowered total serum protein content and elevated A/G ratio in males, and lowered serum alkaline phosphatase activity in females. VP 10 and 30 mg/kg predominantly induced thymic atrophy, testicular atrophy with suppression of spermatogenesis and tubular atrophy, a decrease in epididymal weight, and splenic erythropoiesis. Above-described changes excluding the findings on testis and epididymis in VP 30 mg/kg group were shown to be generally reversible. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 1 mg/kg/day against rats of both sexes.

Administration, Oral↗

PubMed1986

[Toxicity studies of VP 16-213 (IV)--Intravenous one-month subacute toxicity in rats].

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.15, 0.50, 1.5 and 4.5 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at dose levels of 0.04 and 0.08 mg/kg/day. The summarized results obtained are as follows: VP 0.50 mg/kg and higher suppressed body weight increase and food intake dose-responsively. VP 4.5 mg/kg brought depilation and anemia, and some of male animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 0.50 mg/kg and higher decreased white blood cell count accompanied with lowered lymphocyte fraction, and 1.5 and 4.5 mg/kg predominantly decreased red blood cell count. VP 1.5 and 4.5 mg/kg lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 0.50 mg/kg and higher predominantly decreased testicular weight, and 1.5 and 4.5 mg/kg predominantly brought thymic atrophy, hypoplasia of bone marrow and testicular atrophy with suppression of spermatogenesis and tubular atrophy. VP 4.5 mg/kg induced atrophy of germinal centers and hemosiderosis in spleen, and epididymal atrophy with decrease of sperms in number and appearance of giant cells. Above-described changes excluding the findings on testis and epididymis were generally reversible. Most of the findings for a reference drug, VCR, were similar to those for VP, and their severities brought by VP 1.5 and 4.5 mg/kg were comparable to those by VCR 0.04 and 0.08 mg/kg, respectively. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.15 mg/kg/day against rats of both sexes.

Anemia↗

PubMed1985