Overexpression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD) provides protection against AZT- or 3TC-induced endothelial dysfunction

Antiviral Research
Mitzi GloverTammy R Dugas

Abstract

Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the backbone of current combination therapies for HIV. These therapies have significantly decreased mortality and morbidity in HIV-infected patients, but some are associated with cardiovascular complications, including endothelial dysfunction, an early marker for atherosclerosis. Our prior studies demonstrated that co-treatment of cells with an antioxidant therapy reversed NRTI-induced endothelial injury. Thus, as a proof of concept that mitochondrially-targeted antioxidants may be useful in preventing NRTI toxicity, in the current study, mice overexpressing a mitochondrial antioxidant, manganese superoxide dismutase (MnSOD), were compared with wild-type (WT) mice. Mice were treated chronically with either zidovudine (AZT), lamivudine (3TC), or tenofovir (TDF) to determine whether overexpression of MnSOD protected them from endothelial dysfunction. Endothelial function was assessed using vessel reactivity experiments on thoracic aortas as well as measures of endothelium derived factors nitric oxide (NO), endothelin-1 (ET-1), and prostacyclin. Oxidative stress was evaluated as levels of plasma 8-isoprostane. Alterations in vessel reactivity, NO, and ET-1 in WT mi...Continue Reading

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Citations

Jul 2, 2016·Neurotoxicity Research·Ankit ShahAnil Kumar
Jul 28, 2016·Environmental and Molecular Mutagenesis·Yongmin LiuMiriam C Poirier
Sep 24, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yi-Fan ChenTammy R Dugas
Jun 1, 2018·Oxidative Medicine and Cellular Longevity·Longman Li, Xiaobo Yang
Nov 30, 2016·Journal of Animal Science and Biotechnology·Sung Jae YoonMyung Geol Pang
Nov 2, 2019·Free Radical Biology & Medicine·Anne Negre-SalvayreRobert Salvayre

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