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Teratogenic effects of voriconazole (anti-fungal drug) on Swiss albino mice
Hansa Gupta1, Pradeep Bhatnagar1, Lata Shahani1
1Department of life science and environmental science, Research scholar, Professor and Associate Professor, IIS (deemed to be University), Jaipur, Rajasthan 302020, India.
Abstract:
Antifungals are a class of drugs that target the treatment of invasive fungal infections. This includes polyenes, triazoles, and echinocadins. Among these, azoles are being extensively used nowadays. Triazoles have become standard for the azoles and have replaced amphotericin B as the first line of defence for fungal infections. With the increased cases of fungal infection, which affect a majority of the population at different stages and situations, one such section of the population is pregnant females. The rate and susceptibility of fungal infections are particularly higher in pregnant females, as the immunity of the mother is highly compromised. Systemic fungal infections like invasive aspergillosis, esophageal candidiasis, and candidemia are being treated with new age triazole antifungals like voriconazole. Prolonged and high concentrations of this drug are associated with various developmental anomalies. With this aim, teratogenic studies were performed on pregnant female mice during gestation and the weaning/lactation period to observe the effects of voriconazole at different dosages (8 mg/kg b.w., 10 mg/kg b.w., and 20 mg/kg b.w.). Pregnant dams were subjected to 20 mg/kg b.w. Voriconazole had a small litter size and a high number of resorptions. Craniofacial defects in the form of reduced ossification and widely open sutures, the presence of the 14th rib, asymmetry in the sternebrae, and the absence of ossified distal phalanges were some of the skeletal anomalies which were significant in the foetus and pups subjected to both 10 mg/kg b.w. and 20 mg/kg b.w. doses of voriconazole.
Insights
Voriconazole, a triazole antifungal, caused developmental anomalies in mouse fetuses and pups. High doses led to skeletal defects, reduced litter size, and increased resorptions during pregnancy.
Area of Science:
- Pharmacology
- Developmental Toxicology
- Mycology
Background:
- Antifungal drugs, including triazoles, are crucial for treating invasive fungal infections.
- Pregnant women are more susceptible to fungal infections due to compromised immunity.
- Voriconazole is a new-age triazole antifungal used for systemic infections but may cause developmental anomalies.
Purpose of the Study:
- To investigate the teratogenic effects of voriconazole in pregnant mice.
- To evaluate the impact of different voriconazole dosages on fetal development and offspring health.
Main Methods:
- Teratogenic studies were conducted on pregnant mice during gestation and lactation.
- Mice were administered varying doses of voriconazole (8, 10, and 20 mg/kg body weight).
- Effects on litter size, resorptions, and skeletal anomalies in fetuses and pups were assessed.
Main Results:
- Voriconazole administration, particularly at 10 and 20 mg/kg, resulted in significant skeletal anomalies.
- Observed defects included reduced ossification, widely open sutures, extra ribs, sternal asymmetry, and absent phalanges.
- Higher doses also led to smaller litter sizes and increased resorptions.
Conclusions:
- Voriconazole exposure during pregnancy is associated with significant teratogenic effects, including skeletal malformations.
- These findings highlight potential risks of voriconazole use in pregnant populations.
- Further research is needed to understand the precise mechanisms and clinical implications.

