Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats
| Autor: | Patricia E. Losco, Dineshwar Sinha, Preston Davis, Mary Ellen Lynch, Theodore J. Schmahai, Larisa Reyderman, Amin Nomier, Michael W. Leach, Tarundeep Kakkar |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pituitary gland medicine.medical_specialty 040301 veterinary sciences Uterus Administration Oral Biology Testicle Genitalia Male Toxicology Beagle Pathology and Forensic Medicine 0403 veterinary science Gonadotropin-Releasing Hormone 03 medical and health sciences Random Allocation 0302 clinical medicine Atrophy Dogs Sex Factors Neurokinin-1 Receptor Antagonists Piperidines Species Specificity Internal medicine Acetamides medicine Animals Molecular Biology 030219 obstetrics & reproductive medicine Dose-Response Relationship Drug Reproducibility of Results Rats Inbred Strains Receptors Neurokinin-3 04 agricultural and veterinary sciences Cell Biology Genitalia Female Receptors Neurokinin-2 Aspermia Luteinizing Hormone medicine.disease Rats medicine.anatomical_structure Endocrinology Toxicity Female Endocrine gland |
| Zdroj: | Toxicologic pathology. 35(2) |
| ISSN: | 0192-6233 |
| Popis: | SCH 206272, an antagonist of neurokinin receptors 1, 2, and 3, was administered orally by gavage for 1 month to 8- to 10-month-old dogs at doses of 0, 15, 30, or 60 mg/kg, and to 6-week-old rats at doses of 0, 30, 100, or 300 mg/kg. The most important changes occurred in the reproductive tract of the dogs at all doses. Absolute and relative group mean organ weights for the testes, prostate gland, epididymides, ovaries, and uterus were 33–86% lower than concurrent controls in groups receiving SCH 206272. Organ weight changes were not dose-related. Microscopic changes that correlated with the organ weight changes occurred in all groups receiving SCH 206272. For males, they included minimal to severe atrophy of the testes, epididymides, and prostate gland. In addition, the epididymides exhibited severe oligospermia or aspermia, minimal epithelial apoptosis and mild epithelial vacuolation. In female dogs, the ovaries and uteri appeared immature. Microscopic changes were similar in incidence and severity in dogs receiving 30 or 60 mg/kg, but were slightly less in dogs receiving 15 mg/kg. In contrast, similar findings were not observed in the reproductive tract of male or female rats, despite overlapping systemic, hypothalamic, and pituitary gland concentrations of SCH 206272. |
| Databáze: | OpenAIRE |
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