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Titolo:
Repeated analysis of semen parameters in beagle dogs during a 2-year studywith the HMG-CoA reductase inhibitor, atorvastatin
Autore:
Dostal, LA; Juneau, P; Rothwell, CE;
Indirizzi:
Pfizer Inc, Global Res & Dev, Drug Safety Evaluat, Ann Arbor, MI 48105 USAPfizer Inc Ann Arbor MI USA 48105 Safety Evaluat, Ann Arbor, MI 48105 USA Pfizer Inc, Global Res & Dev, Biostat Discovery & Early Dev Projects, Ann Arbor, MI 48105 USA Pfizer Inc Ann Arbor MI USA 48105 y Dev Projects, Ann Arbor, MI 48105 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 61, anno: 2001,
pagine: 128 - 134
SICI:
1096-6080(200105)61:1<128:RAOSPI>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
MALE HYPERCHOLESTEROLEMIC PATIENTS; TESTICULAR STEROIDOGENESIS; CANINE SEMEN; SIMVASTATIN; PRAVASTATIN; SAFETY;
Keywords:
sperm analysis; male beagle dogs; semen analysis; HMG-CoA reductase inhibitor; atorvastatin; sperm motility;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Dostal, LA Pfizer Inc, Global Res & Dev, Drug Safety Evaluat, 2800 Plymouth Rd, Ann Arbor, MI 48105 USA Pfizer Inc 2800 Plymouth Rd Ann Arbor MI USA 48105 MI 48105 USA
Citazione:
L.A. Dostal et al., "Repeated analysis of semen parameters in beagle dogs during a 2-year studywith the HMG-CoA reductase inhibitor, atorvastatin", TOXICOL SCI, 61(1), 2001, pp. 128-134

Abstract

Sperm analyses are often incorporated into reproductive toxicity studies in rats. Due to the relative ease of collecting multiple samples throughout a study, semen analysis in non-rodents such as dugs offers the opportunity to assess potential development of functional effects of compounds on male reproduction over time. In the present study, semen parameters were evaluated in beagle dogs during and at termination of a chronic toxicity study with the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor atorvastatin. Male dogs received 0, 10, 40, or 120 mg/kg orally in gelatin capsules for up to 104 weeks (n = 10/group). After 52 weeks of dosing, 3 dogs/group were euthanized, and 2/group were withdrawn from treatment for a 12-week reversal period and euthanized at Week 64. The remaining 5/group continued treatment until Week 104. Semen was collected from all animals for 3 consecutive weeks prior to termination of the 52-week animals (Weeks 50, 51, 52) for analysis of sperm parameters, using manual methods of evaluation. Semen was collected from the remaining animals at Weeks 64, 78, 91, and 104, and was analyzed. At necropsy, testes, epididymides, and prostates were weighed and evaluated histologically, and epididymal sperm counts were determined. Serum cholesterol was decreased 25-60% at all doses during the study. There were no drug-related differences in semen volume and color, total sperm count, and sperm concentration, morphology, progressiveness, and percent motility during treatment with atorvastatin, There were also no effectson reproductive organ weights or histopathology, and no effects on epididymal sperm count. Thus, incorporation of semen analyses into this study allowed the evaluation of potential male reproductive effects in dogs at multiple time points during the study. Statistical power calculations demonstrated acceptable statistical power (> 80%) for semen sperm count, concentration, morphology, and motility with group sizes of 8-10 animals, and for semen sperm count and concentration or epididymal sperm count with group sizes of3-5 animals, using the methodology described in this paper.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 20:46:59