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Abnormal thymus development and impaired function of the immune system in rats after prenatal exposure to aciclovir
R Stahlmann1, M Korte, H Van Loveren
1Institut für Toxikologie und Embryopharmakologie, Freie Universität Berlin, Federal Republic of Germany.
Insights
Prenatal exposure to aciclovir in rats resulted in abnormal thymus development and altered immune responses to Trichinella spiralis infection. These effects on thymus weight and antibody production highlight potential developmental risks of aciclovir.
Area of Science:
- Developmental toxicology
- Immunology
- Pharmacology
Background:
- Aciclovir is a widely used antiviral medication.
- Prenatal exposure to certain drugs can impact offspring development and immune function.
Purpose of the Study:
- To investigate the effects of prenatal aciclovir exposure on thymus development and immune system function in rats.
- To assess the impact of aciclovir on host resistance to Trichinella spiralis infection.
Main Methods:
- Pregnant rats were administered aciclovir on day 10 of gestation.
- Offspring were assessed for thymus and organ weights.
- Immune response was evaluated using a Trichinella spiralis infection model, measuring antibody titers and parasite burden.
Main Results:
- Prenatal aciclovir exposure led to reduced thymus weight in offspring.
- Liver weight decreased, while spleen weight increased in some treatment groups.
- Altered IgM antibody titers were observed post-infection, with higher levels early on.
Conclusions:
- Aciclovir exposure during gestation can cause abnormal thymus development in rats.
- Prenatal aciclovir exposure modifies the immune response to parasitic infection.
- Further research is needed to understand the long-term implications of these findings.
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)