Aims:This study was designed to evaluate the effects of Efavirenz-based highly active antiretroviral therapy (EFV b -HAART, Efavirenz/Lamivudine/Tenofovir) with emphasis on survival, longevity, climbing ability, and reproductive capacity in D. melanogaster. Methods: The experiments were carried out at the Africa Center of Excellence in Phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria between January 2017 and August 2018. D. melanogaster (both sexes) 1-4 days old were exposed to different concentrations of EFV b -HAART (range 10-1200 mg) in the fly food for initial 7 days to determine the LD 50 , then 5 day fly exposure to 93.11 mg, 46.56 mg, 23.28 mg or 11.64 mg for negative geotaxis assay, and acetylcholinesterase (AChE) activity. Furthermore, 28-day fly survival and longevity were determined. Statistical significance was presumed at P< 0.05. Iorjiim et al.; JABB, 23(1): 26-38, 2020; Article no.JABB.54451 27 Results: The LD 50 of EFV b -HAART in D. melanogaster was 93.11 mg. The HAART exposed flies showed significantly (P<0.001) increased mortality, significant (P<0.001) decreased fly eclosion, acetylcholinesterse (AChE) activity and climbing ability compared to unexposed group at all experimental concentrations. Conclusion: The decreased 28-day survival, longevity, climbing ability and reproductive capacity at all experimental concentrations may be attributable to the deleterious effects of EFV b -HAART in D. melanogaster. Our findings suggest that long term use of EFV b -HAART by HIV patients may be associated with accelerated aging, decreased life expectancy, quality of life (due to possible neurotoxicity) and reproductive competence, as evidenced by increased mortality, reduced longevity, AChE activity, and 100% emergence failure respectively in D. melanogaster, and may require further study in humans. We recommend further research to expound the biochemical and molecular toxicodynamics of EFV b -HAART in D. melanogaster with the view of ameliorating same. Original Research Article
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.
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