Browsing by Author "Nzuza, Sanelisiwe."

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Naringing reverses HIV-1 protease inhibitors-associated pancreatic beta-cell dysfunction in vitro.
Nzuza, Sanelisiwe.; Owira, Peter Mark Oroma.
Introduction: Chronic exposure to HIV-1 Protease Inhibitors (PIs) has been associated with pancreatic β-cell dysfunction and impairment of insulin secretion. PIs have been suggested to induce β-cell dysfunction through increasing oxidative stress leading to impaired insulin secretion. The study investigated whether naringin, a naturally occurring antioxidant, could reverse PIs-induced β-cell dysfunction by reducing oxidative stress. Methods: The RIN-5F cells were cultured in RPM1-1640 medium, allowed to grow to 80% confluence, exposed to different concentrations of PIs [nelfinavir (1-10 μM), saqanavir (1-10 μM) and atazanavir (5-20 μM)] in the presence of 11 mM glucose for 24 hr then subjected to insulin ELISA assay to assess dose-dependent suppression of insulin of secretion by PIs. To determine glucose-induced insulin secretion, the cells were exposed to nelfinavir (10 μM), saquinavir (10 μM), atazanavir (20 μM) 24 hr with or without glibenclamide (10 μM) in the presence of varying glucose concentrations (11-25 mM) then harvested and subjected to biochemical assays for the measurement of insulin levels, lipid peroxidation, ATP generation, Glutathione levels (GSH), Superoxide dismutase (SOD) and caspase-3 and -9 activities. Cells were further exposed to naringin (0-50 μM) in the presence of 11 mM glucose for 24 hr then subjected to insulin ELISA for insulin secretion determination. To investigate the role of PIs relative to naringin on RIN-5F cells, the cells were exposed to nelfinavir (10 μM), saquinavir (10 μM) and atazanavir (20 μM) with or without naringin (10 μM) also in the presence of 11 mM for 24 hr and similarly subjected to biochemical assays. Results: Linear regression analysis showed significant decrease in insulin levels in response to nelfinavir, saqunavir and atazanavir (r2= 0.86, 0.76, 0.95, respectively) in a dose-dependent manner. PIs significantly (p < 0.05) reduced insulin secretion and ATP production, increased lipid peroxidation, SOD and caspase-3 and -9 activities and also reduced GSH in a glucosexv dependent manner. These effects were reversed by glibenclamide. Naringin (0-50 μM) caused dose-dependent increased in insulin secretion and also reduced lipid peroxidation, SOD, caspase-3 and -9 activities, increased GSH and ATP levels in cells that were exposed to PIs. Conclusion: PIs induced β-cell dysfunction and impairment of insulin secretion by increasing oxidative stress and ATP depletion. Naringin ameliorated PIs-induced impairment of β-cell dysfunction by reducing oxidative stress.