-Zidovudine (3'-Azido-2', 3'-dideoxythymidine, AZT, ZDV) is routinely used as one of the component of antiretroviral therapy to prevent transmission of the HIV infection from mother to child. The drug, when given during pregnancy can give rise to myriad toxicities as reported in previous studies on human, animal and in-vitro experiments. The present study was an attempt to explore the Zidovudine teratogenesis in F1 and F2 generation of mice following initial maternal exposure to Zidovudine during pregnancy, through delivery and lactation. The F1 generation actually would have got the exposure during embryonic development and infant stages. Pregnant Swiss mice were treated orally with ZDV 50 mg/ kg/day or distilled water (control), from day eighth of gestation, through delivery and continued for first ten days of lactation. The F1 generation litters were raised and mated to produce F2 generation mice. An interesting phenotype of "healthy" and "sick" was noted in F2 generation but not in the F1 generation. In F2 generation 35% died on different postnatal day during 120 days of follow up period. Chromosomal study from bone marrow of F1 and F2 showed various chromosomal aberrations. Lipodystrophy and hepatotoxicity was observed in "sick" mice. The study generated a hypothesis of recessive mutation and concludes that Zidovudine is a transplacental genotoxic agent. The result of present study therefore suggests the need to study the effect of zidovudine in human subjects for a longer period of time to rule out similar genotoxic effect.
Objective: Zidovudine, the first antiretroviral drug is used to prevent vertical transmission of HIV infection. Without any adequate proof of its safety to fetus, the drug was administered to pregnant women. The present experiment aims to study at the light microscopic level, the effect of zidovudine in fetus exposed in-utero to the drug. Material and method: Sixty Swiss mice were divided into two groups of control (n=20) and experimental (n=40). A dose of 50 mg/kg/day was administered orally to experimental group and an equivalent amount of normal saline to control group. Drug was administered from day 8 to day 16 of gestation and on day 19 the animal was sacrificed. Fetus collected after laparotomy were fixed in 10% neutral formalin and then subjected to light microscopic study to assess the histopathological changes. H&E stained sections of liver, lung, kidney, brain and maternal ovary was analysed. Result: Fatty degeneration of liver, degenerative changes in kidney section, dilatation of alveoli with thinning of alveolar wall, microcystic degeneration in cerebral cortex was observed. The maternal ovary of experimental group had small corpus luteum. Conclusion: Multiple tissues are affected by in-utero administration of ZDV. Further study at ultrastructural level is needed.
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