Abnormal thymus development and impaired function of the immune system in rats after prenatal exposure to aciclovir

Abstract

Aciclovir (synonym: acyclovir) causes abnormal thymus development in rats. After treatment on day 10 of gestation a weight reduction of the organ is obvious in 21-day-old fetuses which persists postnatally. Adult male rats exposed in utero to one or three injections of 100 mg aciclovir/kg body wt given to the dam on day 10 of pregnancy showed a reduction of the thymus weight to 333 +/- 158 mg and 276 +/- 61 mg (control: 428 +/- 92 mg; n = 10). Corresponding alterations were detectable in female offspring. Liver weight was also decreased and spleen weight (in relation to body wt) was significantly increased in the offspring after the three exposures. In a host resistance model with Trichinella spiralis the function of the immune system of rats prenatally exposed to aciclovir was examined. Six weeks postnatally 10-12 randomly selected male rat offspring of one control and two treatment groups (1 or 3 injections of 100 mg aciclovir/kg body wt on day 10 of gestation) were infected orally with 500 Trichinella spiralis muscle larvae. Before and several times after the infection blood was taken from a tail vein or obtained by decapitation for examination of the antibody titers (IgM, IgG, IgA, IgE) to antigens of T. spiralis. Six weeks after the infection the weight of relevant organs was determined and tongue preparations were used for T. spiralis muscle larvae counting. Aciclovir exposed animals showed a different immune response than control rats. IgM titers in both treatment groups were higher than in controls two weeks after the infection but not different by the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of humoral and cell mediated immune response modulation by chemical and bio‐pesticides

“…The low antibody titres in the chemical pesticide treated animals on all the days of the tests showed that both the IgM as well as IgG development is suppressed by chemical pesticides treatment even when pesticides are inoculated at subchronic and sublethal doses. Our findings agree with those of Stahlmann et al [5], who found a dose dependent decrease in IgG in rats exposed to acyclovir, and with Banerjee et al [6] who found that aldrin and DDT suppressed both IgG and IgM levels in the pesticide-exposed rats. However, our findings contrast with those of Founier et a/.…”

Developmental immunotoxicity (DIT) testing of pharmaceuticals: Current practices, state of the science, knowledge gaps, and recommendations

“…Examples of developmental immunotoxicity assessments with pharmaceutical compounds, including cyclosporine, dexamethasone, diazepam, aciclovir, and diethylstilbestrol (DES), have been described (Stahlmann et al, 1992;Schlumpf et al, 1989Schlumpf et al, , 1994Dietert et al, 2003;Fenaux et al, 2004;Hussain et al, 2005;Barrow et al, 2006;Luebke et al, 2006). Recently, it was suggested that the United States (US) Food and Drug Administration (FDA) has possibly observed a case of differential sensitivity where juvenile animals displayed effects not observed in toxicity studies conducted in the adult; however, due to confidentiality, no specific information could be shared.…”

Assessing immunotoxicity: guidelines

“…In some offspring the thymus could no longer be detected [20]. Effects on T‐cell mediated responses were observed in a host resistance model in which the exposed offspring showed a decreased resistance to Trichinella spiralis (a highly T‐cell dependent defence model) [21]. In some cases acyclovir is prescribed to pregnant women.…”