Involvement of functional senescence in efavirenz-induced toxicity in fruit fly

Background: We aimed in this article to assess the likeliness of efavirenz to induce functional senescence in Drosophila melanogaster (fruit fly).Methods: Ten different concentrations of EFV were mixed with fly food and fed to 3-day-old flies orally for a 7 day LC50 calculation. Drug concentrations from LC50 were selected for a 28 day survival to determine the duration of treatment for behavioral and biochemical assays. A 5day feeding plan was used to investigate the effects of the drug on organismal, neuromuscular, reproductive, and metabolic senescence. An in silico study was executed to decipher a molecular interaction of Drosophila enzymes glutathione-s-transferase (GST) or acetylcholinesterase (AChE) with EFV.Results: The calculated LC50 of EFV was 118 mg/10-g fly diet. The test drug induced a significant (P < 0.05) increase in fly mortality, climbing difficulty, and procreative deficits after a 5 day oral exposure. Similarly, there were significant (P < 0.05) biochemical alterations, which suggested in vivo biochemical damage against total thiols (T-SH), SOD (superoxide dismutase), CAT (catalase), GST, AChE, and MDA (malondialdehyde) in the test flies compared to the control groups. In silico study revealed a significantly (P < 0.05) higher binding energy between EFV and the active amino acids of fly AChE and GST when compared to the substrates or standard inhibitors respectively.Conclusion: EFV exhibited ecotoxic potentials evidenced by age-related deficits in the fly's functional integrity such as sluggish movement, procreative deficiency, increased mortality, and oxidant-antioxidant inequality. Results from in silico study suggested antagonism against GST and AChE activities as a likely mechanism of EFV-induced toxicity in the fruit fly.