School of Medicine and Health Sciences Poster Presentations
Enhanced Systemic Oxidative/Nitrosative Stress and Cardiac Dysfunction in HIV-1 Transgenic Rats Receiving Combination Anti-retroviral Drug Therapy (cART)
Poster Number
158
Document Type
Poster
Publication Date
3-2016
Abstract
Introduction: We determine if clinically used cART treatment promoted systemic oxidative/nitrosative stress and cardiac toxicity in HIV-1 transgenic rats (Tg).
Methods: A protease inhibitor-based cART (atazanavir-ritonavir plus Truvada) was given orally to control (Fischer-344) and HIV-1-Tg rats at doses similar to human equivalent for 18 weeks. Plasma samples were obtained from tail-bleeding every 6 weeks; cardiac function was obtained by echocardiography.
Results: cART treatment for 6 weeks led to a 40% increase in plasma 8-isoprostane (in vivo lipid peroxidation indicator) level in controls, but to a 2.6-fold elevation in HIV-1-Tg rats. Correspondently, RBC-GSSG level of cART-Tg-rats was increased 2.5-fold vs 1.4-fold for cART-controls. HIV-1-Tg rats displayed significantly higher (25-35%) levels of total plasma triglyceride and cholesterol; after 12 weeks, both lipid levels were further elevated (40-60%) in the cART-Tg-group but not in the control rats. At 18 weeks, cART treatment induced a 17.5% (P3-fold) basal superoxide anion activity compared to the other groups. In association, significantly higher levels (>3-fold vs. other groups) of plasma nitrotyrosine were found in the cART-Tg group. At the cardiac level, intensive staining for nitrotyrosine was seen in peri-vascular connective tissue of ventricles from cART-Tg rats consistent with increased nitrosative stress. Echocardiography detected small (p
Conclusion: HIV-1 expression conferred higher degrees of susceptibility to cART-induced oxidative/nitrosative stress and cardiac dysfunction, in part due to impaired Nrf2-mediated antioxidant response; increased HO-1 and iNOS expressions were due to excessive inflammatory/oxidative stress and might also contribute to elevated peroxynitrite formation in the cART-Tg rats (Supported by NIH-R21-HL-125038, and McCormick Center Genomic Supplemental Fund).
Creative Commons License
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Open Access
1
Enhanced Systemic Oxidative/Nitrosative Stress and Cardiac Dysfunction in HIV-1 Transgenic Rats Receiving Combination Anti-retroviral Drug Therapy (cART)
Introduction: We determine if clinically used cART treatment promoted systemic oxidative/nitrosative stress and cardiac toxicity in HIV-1 transgenic rats (Tg).
Methods: A protease inhibitor-based cART (atazanavir-ritonavir plus Truvada) was given orally to control (Fischer-344) and HIV-1-Tg rats at doses similar to human equivalent for 18 weeks. Plasma samples were obtained from tail-bleeding every 6 weeks; cardiac function was obtained by echocardiography.
Results: cART treatment for 6 weeks led to a 40% increase in plasma 8-isoprostane (in vivo lipid peroxidation indicator) level in controls, but to a 2.6-fold elevation in HIV-1-Tg rats. Correspondently, RBC-GSSG level of cART-Tg-rats was increased 2.5-fold vs 1.4-fold for cART-controls. HIV-1-Tg rats displayed significantly higher (25-35%) levels of total plasma triglyceride and cholesterol; after 12 weeks, both lipid levels were further elevated (40-60%) in the cART-Tg-group but not in the control rats. At 18 weeks, cART treatment induced a 17.5% (P3-fold) basal superoxide anion activity compared to the other groups. In association, significantly higher levels (>3-fold vs. other groups) of plasma nitrotyrosine were found in the cART-Tg group. At the cardiac level, intensive staining for nitrotyrosine was seen in peri-vascular connective tissue of ventricles from cART-Tg rats consistent with increased nitrosative stress. Echocardiography detected small (p
Conclusion: HIV-1 expression conferred higher degrees of susceptibility to cART-induced oxidative/nitrosative stress and cardiac dysfunction, in part due to impaired Nrf2-mediated antioxidant response; increased HO-1 and iNOS expressions were due to excessive inflammatory/oxidative stress and might also contribute to elevated peroxynitrite formation in the cART-Tg rats (Supported by NIH-R21-HL-125038, and McCormick Center Genomic Supplemental Fund).
Comments
Presented at: GW Research Days 2016