Testicular effects following in utero exposure to the antivirals acyclovir and ganciclovir in rats.

Autor: Nihi F; Departamento de Fisiologia, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil., Moreira D, Santos Lourenço AC, Gomes C, Araujo SL, Zaia RM, Trevisani NB, de Athayde Pinto L, Moura-Costa DD, de Morais RN, Roma Paumgartten FJ, Martino-Andrade AJ
Jazyk: angličtina
Zdroj: Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2014 May; Vol. 139 (1), pp. 220-33. Date of Electronic Publication: 2014 Feb 04.
DOI: 10.1093/toxsci/kfu024
Abstrakt: In utero exposure to the antivirals acyclovir and ganciclovir has been reported to induce gross structural defects in rat offspring. The present study investigated the effects of maternal antiviral treatment on gestation day 10 on reproductive and nonreproductive organs in male rat offspring with a particular focus on the testes. Vehicle and two doses of acyclovir and ganciclovir, 75 and 300 mg/kg, were administered to rat dams. The total doses were fractioned into three subcutaneous applications (3 × distilled water, 3 × 25 mg/kg, and 3 × 100 mg/kg) that were administered on gestation day 10 at 8:00 a.m., 1:00 p.m., and 6:00 p.m. The antiviral concentrations were measured in the serum of the dams 1 h after the last administration. Exposure to 300 mg/kg ganciclovir induced germ cell deficiency in both fetal and adult testes, an effect that was not seen in any other treatment group. Adult rats exposed in utero to this high ganciclovir dose exhibited Sertoli cell-only tubules intermingled with seminiferous tubules that displayed a normal size and normal cell counts, alterations that resemble focal Sertoli cell-only syndrome in humans. The serum concentrations of ganciclovir were markedly higher than those of acyclovir, particularly at the high dose tested. However, although 300 mg/kg acyclovir did not induce germ cell deficiency, other specific effects were seen in exposed animals, including incomplete eye opening and reduced thymus weight.
Databáze: MEDLINE