Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells

Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells

Autor Franca, L. R. Google Scholar
Leal, M. C. Google Scholar
Sasso-Cerri, E. Autor UNIFESP Google Scholar
Vasconcelos, A. Google Scholar
Debeljuk, L. Google Scholar
Russell, L. D. Google Scholar
Instituição So Illinois Univ
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Resumo Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.
Assunto apoptosis
Idioma Inglês
Data 2000-11-01
Publicado em Biology of Reproduction. Madison: Soc Study Reproduction, v. 63, n. 5, p. 1403-1412, 2000.
ISSN 0006-3363 (Sherpa/Romeo, fator de impacto)
Editor Soc Study Reproduction
Extensão 1403-1412
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000165089000023

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