Reproductive and Oxidative Stress Toxicity of Dolutegravir-Based Combination Antiretroviral Therapy in Drosophila melanogaster
Walter Mdekera Iorjiim, Simeon Omale, Great David Bagu, Steven Samuel Gyang, Emmanuel Taiwo Alemika
Journal of Advances in Medical and Pharmaceutical Sciences · pp. 26–40 · Published 31 Jul 2020
10.9734/jamps/2020/v22i630177Abstract
Background/Objective: Dolutegravir-based highly active antiretroviral therapy (DTG-HAART) is the preferred regimen in the management of HIV/AIDS. However, the reproductive and oxidative stress toxicity of DTG-HAART is unknown. This study was designed to investigate the reproductive and oxidative stress toxicity of DTG-HAART in Drosophila melanogaster. Materials and Methods: We performed all the experiments at the Centre of Excellence in phytomedicine Research and Development (ACEPRD), University of Jos, Nigeria, in 2019. D. melanogaster, (1-4 days old), were fed with ten different concentrations of DTG-HAART (range 15 mg -595 mg) or 1000 mL distilled water per 10 g food for seven days to calculate the LD50, then treated with 93.11 mg, 46.56 mg, 23.28 mg, 11.64 mg or 1000 µL distilled water each per 10 g fly food for five days in five replicates. Subsequently, longevity, fly fecundity, and negative geotaxis evaluated. Also, activities of Acetylcholinesterase, Glutathione-S-transferase, Superoxide dismutase, Catalase, as well as Total thiol, and Malondialdehyde levels were investigated in the whole fly homogenate. Statistical values at P<0.05 were considered significant. Results: The LD50 of DTG-HAART in D. melanogaster was 106.4 mg. The result showed significantly decrease (P<0.001) in mean lifespan, fly emergence, Total thiol content, Acetylcholinesterase, Glutathione-S-transferase, Catalase, and Superoxide dismutase activities in the exposed groups compared to the unexposed. Inversely, the Malondialdehyde level in the test groups was significantly (P<0.001) elevated compared to unexposed. Conclusion: Collectively, our results suggest that DTG-HAART toxicity was associated with reproductive deficits and oxidative stress induction in D. melanogaster, here observed as reduced fly fecundity, mean lifespan, AChE activity, antioxidant parameters, and elevated MDA level. This study, thus, raised concerns for long term use of DTG-HAART by HIV patients.
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Cited by 10
Amagon Leritshimwa, Haruna Abigail Awadzi, Amagon Kennedy, Wanche Ernest Magani, Falang Kakjing Dadul, Bukar Bayero Bukata · European Journal of Medicinal Plants · 2022
ONWUKA KALU CHIMA OKPO, EJIKE FELIX CHUKWURAH · 2025
Walter Iorjiim, Simeon Omale, Great Bagu · Journal of Pharmacology and Toxicology · 2023
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Showing 4 of 10 known citations — external sources report more than can currently be individually listed.
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