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Abstract The prevalence of both prediabetes and cardiovascular diseases (CVD) is a public health concern in high-risk individuals using HIV pre-exposure prophylaxis (HIV-PrEP) treatment. The combined effect of prediabetes and HIV-PrEP use on endothelial function remains underexplored. Hence, the aim of this study was to investigate the effects of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) on endothelial function, oxidative stress, inflammation and lipid markers. Prediabetes was induced using a high-fat high-carbohydrate diet over a 20-week period. Prediabetes diagnosis was confirmed using fasting blood glucose and an oral glucose tolerance test. FTC/TDF was orally administered to the rats for a further 12 weeks. Biochemical analysis was performed using colorimetric assays. The prediabetic animals had higher fasting blood glucose (FBG), vascular endothelial growth factor A (VEGF-A), endothelin-1(ET-1), nitric oxide (NO), NO/ET-1 ratio, hydrogen peroxide (H2O2), interleukin-6, tumour necrosis factor α (TNF-α), triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), endothelial nitric oxide synthase (eNOS), total antioxidant capacity (TAOC) and lower high-density lipoprotein cholesterol (HDL-C) when compared to the non-prediabetic control. However, the FTC/TDF treatment increased VEGF-A, HDL-C, LDL-C and it reduced TGs, NO, NO/ET-1 ratio, H2O2, eNOS, TAOC, interleukin-6, TNF-α and had minimal effect on FBG and ET-1 levels in prediabetic animals .In the non-prediabetic state, FTC/TDF treatment increased VEGF-A, ET-1, NO, NO/ET-1 ratio, H2O2 and interleukin-6 while decreasing eNOS, TAOC, TNF-α and HDL-C and it had a minimal effect on FBG, LDL-C and TGs. FTC/TDF treatment could increase the risk of cardiovascular complications via oxidative stress and endothelial dysfunction. Further studies are needed to fully understand the molecular mechanisms underlying these observed effects.
Maswanganyi et al. (Mon,) studied this question.