Browsing by Author "Symington, Burger"
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- ItemThe effects of HIV protease inhibitors on the rat heart(Stellenbosch : Stellenbosch University, 2016-03) Symington, Burger; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.ENGLISH ABSTRACT: Since the early 1990’s HIV/AIDS emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardiometabolic complications such as type-2 diabetes and acute myocardial infarction. As the underlying mechanisms driving PI-mediated sideeffects remain unclear, this study set out to investigate this intriguing question by employing a rat model of chronic PI treatment (6 months). In addition, various co-treatments (Resveratrol, Aspirin, Vitamin C) were evaluated to ascertain whether such a therapeutic strategy may blunt PI-induced side-effects. Body weights and weight gains, blood metabolite levels, echocardiography and cardiac mitochondrial respiration were assessed. Our data reveal that after 2 months of PI treatment there were no significant changes for the various parameters evaluated in this study. However, after 4 months Vitamin C co-treatment ameliorated the PI-induced decrease in body weight, while it also blunted the PI-mediated inhibition of mitochondrial respiration. Aspirin co-treatment also improved mitochondrial respiration while this effect was not observed with Resveratrol. After 6 months of PI treatment all interventions prevented the PI-induced increase in body weights, while Aspirin and Vitamin C prevented the PI-induced increase in heart weight. At the later time point mitochondrial respiration was, unlike at the 4 month time point, not affected by PI treatment. However, Resveratrol co-treatment significantly increased mitochondrial respiration. This study demonstrates that early PI-mediated perturbations include alterations in body weights and inhibition of mitochondrial respiration. However, no significant changes were found for heart function or blood metabolites. Our findings show that the co-treatments triggered beneficial outcomes by reversing weight changes and enhancing mitochondrial respiratory function. As the co-treatments are already well-known and approved therapeutic agents, we are of the opinion that this study provides significant impetus to test such compounds to establish whether our basic findings can be successfully translated into the clinical setting to eventually improve the overall well-being of HIVpositive patients.
- ItemResveratrol co-treatment attenuates the effects of HIV protease inhibitors on rat body weight and enhances cardiac mitochondrial respiration(Public Library of Science, 2017-01-20) Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.; Essop, M. FaadielSince the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail.