Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 7). Effects of reserpine in 2- and 4-weeks studies.
To assess the efficacy of different period of treatment for evaluating male reproductive toxicity in rats, reserpine was subcutaneously administered on a daily basis to male Sprague-Dawley rats at dosages of 0.05, 0.1 or 0.2 mg/kg for 2 weeks or at dosages of 0.05 or 0.1 mg/kg for 4 weeks. At the end of the administration period the animals were sacrificed and sperm counts, organ weights and histopathological changes in the reproductive organs were examined. The sperm number in the caudal epididymis and genital organ weights were not affected by reserpine with either 2- or 4-weeks treatment. In the 4-weeks study, histopathological examination of the testes revealed retention of step 19 spermatids in the seminiferous tubules of stages IX to XII and decreased secretory content of the prostate in the 0.05 and 0.1 mg/kg groups. In the 2-weeks study, although no distinct histopathological changes were observed in the 0.05 mg/kg group, decreased secretory content of the prostate, apoptosis of spermatocytes in the seminiferous tubules of stage VII and cell debris of the epididymis were observed in the 0.1 and 0.2 mg/kg groups. These results suggested that 2-weeks treatment with reserpine is sufficient for detection of testicular toxicity, although higher dosage levels are appropriate than for 4-weeks treatment.
Yamauchi
K
K
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Yodogawa, Osaka 532-8514, Japan.
Takaura
Y
Y
Noto
T
T
Saegusa
T
T
Nakatsuji
S
S
Ohishi
Y
Y
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000008:administration & dosage / Q000633:toxicity*; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013076:Sperm Count; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests
D014150:Antipsychotic Agents; D012110:Reserpine