Effect of antiretroviral drugs on the DNA damage in mice

Environ Toxicol Pharmacol. 2014 Jan;37(1):390-5. doi: 10.1016/j.etap.2013.12.011. Epub 2014 Jan 1.

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.

Keywords: Antiretroviral drugs; Comet assay; DNA damage; Efavirenz; Micronucleus test; Nevirapine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Animals
  • Anti-HIV Agents / toxicity*
  • Benzoxazines / toxicity*
  • Bone Marrow Cells / cytology
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism
  • Comet Assay
  • Cyclopropanes
  • DNA Damage
  • Erythrocytes / drug effects
  • Liver / cytology
  • Male
  • Mice
  • Micronucleus Tests
  • Myocardium / cytology
  • Nevirapine / toxicity*
  • Reverse Transcriptase Inhibitors / toxicity*

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • efavirenz