Mitochondrial compromise in 3-year old patas monkeys exposedin uteroto human-equivalent antiretroviral therapies
Autor: | Ruth A. Woodward, Rao L. Divi, Alexander T. Gibbons, Yongmin Liu, Eunwoo Shim Park, Miriam C. Poirier, Eric Shide |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Nevirapine Epidemiology Offspring Health Toxicology and Mutagenesis Physiology Pharmacology 03 medical and health sciences Zidovudine 0302 clinical medicine immune system diseases Patas monkey Abacavir Medicine 030212 general & internal medicine Genetics (clinical) biology business.industry Erythrocebus patas virus diseases Lamivudine biology.organism_classification 030104 developmental biology In utero business medicine.drug |
Zdroj: | Environmental and Molecular Mutagenesis. 57:526-534 |
ISSN: | 0893-6692 |
Popis: | Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P |
Databáze: | OpenAIRE |
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