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Updated: May 3, 2026
Humanized NOG Mice for Intravaginal HIV Exposure and Treatment of HIV Infection
Published on: January 31, 2020
Effect of antiretroviral drugs on the DNA damage in mice
Hugo Martins de Oliveira1, Adriani Paganini Damiani1, Renata de Oliveira Dias1
1Laboratório de Biologia Celular e Molecular-LABIM, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
Abstract:
In order to investigate the effects of two non-nucleoside reverse transcriptase inhibitors (NNRTIs) on the DNA damage in vivo, nevirapine (NVP; 3.3 mg/kg), efavirenz (EFV; 10 mg/kg) or saline were administered orally. Acute effects were analyzed 24 h after the administration of a single NNRTI dose, and subchronic effects 24 h after the last dose. Peripheral blood, brain, heart and liver samples were subjected to genotoxicity analyses and polychromatic erythrocytes from the bone marrow to micronucleus test. The micronucleus test did not reveal any significant differences between animals from the acute or subchronic groups. Comet assay showed that acute and subchronic NNRTI treatment did not cause any significant DNA damage in heart, liver or peripheral blood cells. However, increased damage indexes and frequencies were observed in the brain of mice, subchronically treated with EFV. This result suggests for the first time that this drug might induce genotoxicity in the brain.
Insights
This study found that while nevirapine and efavirenz (non-nucleoside reverse transcriptase inhibitors) did not cause DNA damage in most tissues, efavirenz may induce genotoxicity in the brain after subchronic exposure.
Area of Science:
- Pharmacology
- Toxicology
- Neuroscience
Background:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are crucial antiretroviral drugs.
- Understanding the genotoxic potential of NNRTIs is essential for patient safety.
- Previous studies have not fully elucidated the in vivo genotoxicity of NNRTIs, particularly in the central nervous system.
Purpose of the Study:
- To investigate the in vivo genotoxicity of nevirapine (NVP) and efavirenz (EFV) in mice.
- To assess both acute and subchronic effects of NNRTI administration on DNA damage.
- To evaluate potential neurotoxic effects of these antiretroviral drugs.
Main Methods:
- Oral administration of NVP (3.3 mg/kg) or EFV (10 mg/kg) or saline to mice.
- Genotoxicity assessment using the micronucleus test and comet assay.
- Analysis of peripheral blood, brain, heart, and liver tissues at acute (24h post-single dose) and subchronic (24h post-last dose) time points.
Main Results:
- The micronucleus test showed no significant genotoxicity for either NNRTI in any tissue.
- Comet assay revealed no significant DNA damage in heart, liver, or peripheral blood cells after acute or subchronic NNRTI treatment.
- Subchronic EFV administration significantly increased DNA damage indexes and frequencies in the brain.
Conclusions:
- Neither NVP nor EFV demonstrated significant genotoxicity in peripheral blood, heart, or liver tissues.
- Subchronic exposure to EFV may induce genotoxicity specifically within the brain.
- This study highlights a potential neurotoxic risk associated with long-term efavirenz use, warranting further investigation.
