Effect of antiretroviral drugs on the DNA damage in mice |
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Affiliation: | 1. Laboratório 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;2. Laboratório de Imunologia, Programa de Pós-Graduação em Ciências da Saúde, Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil;1. IFISE, CONICET-UNR, Rosario, S2002LRL, Argentina;2. IBR, CONICET-UNR, Rosario, S2002LRL, Argentina;3. Facultad de Ciencias Médicas, Universidad Nacional de Rosario (UNR), Rosario, S2002LRL, Argentina;4. Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Rosario, S2002LRL, Argentina;1. Laboratório de Histologia e Patologia, Departamento de Biologia e Farmácia, Universidade de Santa Cruz do Sul, Santa Cruz do Sul, Rio Grande do Sul, Brazil;2. Curso de Ciências Biológicas, Departamento de Biologia e Farmácia, Universidade de Santa Cruz do Sul, Santa Cruz do Sul, Rio Grande do Sul, Brazil;3. Programa de Pós-Graduação em Biologia Celular e Molecular, Universidade Federal do Rio Grande do Sul, Campus do Vale, Porto Alegre, Rio Grande do Sul, Brazil;4. Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;5. Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;1. Pharmacology Laboratory, Pharmacy Department, Faculty of Technology and Engineering, The M.S. University of Baroda, India;2. Pharmaceutical Quality Assurance Laboratory, Pharmacy Department, Faculty of Technology and Engineering, The M.S. University of Baroda, India;1. Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, 92 North 2nd Road, Heping District, Shenyang, China;2. Department of Otolaryngology, First Affiliated Hospital of China Medical University, Shenyang, China;3. Department of Occupational and Environmental of Health, Dalian Medical University, No. 9 Western Section of Lushun South Road, Dalian, Liaoning, China;4. Department of Occupational and Environmental of Health, School of Public Health, China Medical University, Shenyang, China |
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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. |
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Keywords: | Antiretroviral drugs Efavirenz Nevirapine Micronucleus test Comet assay DNA damage |
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