Co-administration of HAART and antikoch triggers cardiometabolic dysfunction through an oxidative stress-mediated pathway

Abstract

Background Antikoch and highly active anti-retroviral therapy are effective drugs in the management of tuberculosis and Human Immunodeficiency Virus, respectively. However, these cocktails have been independently associated with the aetiopathogenesis of metabolic syndrome. This study investigated whether or not the co-administration of antikoch and anti-retroviral, as seen in tuberculosis/Human Immunodeficiency Virus co-infection, will produce a similar effect. Also, it evaluated the role of glutathione and adenine deaminase/xanthine oxidase/uric acid signaling in antikoch/anti-retroviral-induced cardiometabolic dysfunction. Methods Male rats of Wistar strain were randomized into four groups: the control, which had 0.5 mL of distilled water as a vehicle, anti-Koch-treated rats that were administered a cocktail of anti-Koch, HAART-treated rats that had a combination of anti-retroviral drugs, and anti-Koch + HAART-treated rats that had treatments as anti-Koch-treated and HAART-treated rats. The treatment was once daily and lasted for eight weeks. One way-analysis of variance followed by Tukey’s posthoc test was used to test for significance and pairwise comparisons respectively. Results Although no changes in body weight gain and cardiac weight were noted, it was found that antikoch and/or HAART caused insulin resistance and elevated blood glucose level. In addition, antikoch and/or HAART led to dyslipidaemia, increased atherogenic indices, and elevated cardiac injury markers. These were accompanied by increased plasma and cardiac concentrations of malondialdehyde and nitric oxide, C-reactive protein, and myeloperoxidase activity, as well as suppressed activities of glutathione peroxidase and glutathione-S-transferase, and a fall in reduced glutathione level. The observed alterations were more pronounced in animals that received a combination of antikoch and HAART. Conclusions This study provides the first evidence that antikoch and/or HAART induce cardiometabolic dysfunction via glutathione suppression and up-regulation of adenine deaminase/xanthine oxidase/uric acid-dependent oxidative stress and inflammatory response. These events were associated with dyslipidaemia and increased atherogenic indices. This infers that regular monitoring of glucose level, insulin sensitivity, lipid profile, and oxido-inflammatory markers is important in patients on antikoch and/or HAART for prompt diagnosis and management of cardiometabolic disorder if it ensues.

Oxidative stress, microparticles, and E-selectin do not depend on HIV suppression

“…20 ). Moreover, there is evidence that key antioxidant enzymes may be inhibited by antiretrovirals or their metabolites 1,2,31,42 , indicating they might further potentiate the functional activity of ROS.…”

Zinc improves sexual performance and erectile function by preventing penile oxidative injury and upregulating circulating testosterone in lead-exposed rats

“…Penile xanthine oxidase (XO) activities (Fortress Diagnostic, Antrim, UK), and uric acid (UA) concentrations (Precision Kit, India) were analyzed by colorimetric methods using standard assay kits. XO assay was based on the color intensity generated from the oxidation of xanthine to H 2 O 2 by XO [ 39 ], while UA assay was based on the conversion of UA by uricase into allantoin, carbon dioxide, and hydrogen peroxide that gives a color indicator reaction that is measured at a wavelength of about 520 nm with the action of hydrogen peroxidase [ 48 , 49 ].…”

Factors Influencing Survival Status of HIV/AIDS after HAART in Huzhou City, Eastern China

“…HAART can effectively reduce the mortality risk of HIV/AIDS, improve quality of life, and reduce the risk of opportunistic infections [ 8 , 9 ]. The main purpose of HAART for patients is to inhibit the replication of HIV, reduce the viral load to the lower limit of detection, increase the CD4 + T lymphocyte count (CD4), rebuild or maintain immune function, prolong survival, and improve the quality of life [ 10 ].…”