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

Abstract

We aimed in this article to assess the likeliness of efavirenz to induce functional senescence in Drosophila melanogaster (fruit fly). Ten different concentrations of EFV were mixed with fly food and fed to 3-day-old flies orally for a 7day LC50 calculation. Drug concentrations from LC50 were selected for a 28day 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. The calculated LC50 of EFV was 118mg/10-g fly diet. The test drug induced a significant (P<0.05) increase in fly mortality, climbing difficulty, and procreative deficits after a 5day 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. 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.