Reproductive and Oxidative Stress Toxicity of Dolutegravir-Based Combination Antiretroviral Therapy in Drosophila melanogaster
Walter Mdekera Iorjiim *
Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria.
Simeon Omale
Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria and Africa Centre of Excellence in Phytomedicine Research and Development, University of Jos, Jos, Nigeria.
Great David Bagu
Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria.
Steven Samuel Gyang
Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria.
Emmanuel Taiwo Alemika
Africa Centre of Excellence in Phytomedicine Research and Development, University of Jos, Jos, Nigeria and Department of Pharmaceutical and Medicinal Chemistry, University of Jos, Jos, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: Dolutegravir, superoxide dismutase, Drosophila melanogaster, malondialdehyde