Highly Active Antiretroviral Therapy Depletes Some Antioxidant Parameters and Increases Free Radical Generation in Drosophila melanogaster

Objective: This study intended to evaluate the toxic effects of Efavirenz-based highly active antiretroviral therapy (EFVb-HAART) on some antioxidant parameters, and free radical generation in D. melanogaster.

Materials and Methods: The study was carried out at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019. Sixty (60) D. melanogaster (both sexes) 1-4 days old were exposed by ingestion to graded concentrations of EFVb-HAART (93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg) or 1000 mL distilled water (control) each per 10 g fly food for five days. All concentrations were diluted with 1000 mL distilled water and incorporated in cold fly food in five replicates. Treated flies were anesthetized under ice, homogenized, centrifuged, and the supernatant used to assay for Total protein, Total thiol, Glutathione-S-transferase, Catalase, Superoxide dismutase, and Malondialdehyde levels. Statistical significance was accepted at P< 0.05.

Results: The result showed significantly (P<0.05) increased total protein (1.05±0.0 - 1.34±0.12 Vs. 0.56±0.14 mg/ml) and Malondialdehyde levels (1.63±0.20 – 3.72±0.53 Vs. 0.79±0.10 units/mg protein) in all tested groups versus unexposed. Conversely, Total thiol content (1.96±0.33-0.38±0.10 Vs. 5.31±0.31 units/mg protein) Glutathione-S-transferase (2.20±0.30-1.01±0.27 Vs. 4.31±0.24 units/mg protein), Catalase (171.70±50.13-104.34±9.56 Vs. 368.00±7.56 units/mg protein) and Superoxide dismutase (3.18±0.29-1.44±23 Vs. 5.34±1.35 units/mg protein) activities all decreased significantly (P<0.05) as concentrations increased in all test groups versus unexposed.

Conclusion: Overall, our results suggest that the mechanism of EFVb-HAART toxicity involves sterile immune response observed as increased protein contents, oxidative stress evidenced by depleted oxidative stress-antioxidant parameters, and possible free radical generation shown by increased malondialdehyde levels. Human-based studies are required for deeper understanding of these EFVb-HAART toxicities.