Affordable Access

Publisher Website

Senescence and oxidative stress toxicities induced by lamivudine and tenofovir in Drosophila melanogaster.

Authors
  • Iorjiim, W M1
  • Omale, S2
  • Etuh, M A3
  • Ubani, A4
  • Alemika, E T5
  • Gyang, S S6
  • 1 Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria. Electronic address: [email protected]. , (Niger)
  • 2 Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria; Africa Centre of Excellence in Phytomedicine Research and Development, University of Jos, Jos, Nigeria. , (Niger)
  • 3 Department of Zoology (Applied Entomology and Parasitology), University of Jos, Jos, Nigeria. , (Niger)
  • 4 Department of Pharmaceutical and Medicinal Chemistry, University of Jos, Jos, Nigeria. , (Niger)
  • 5 Africa Centre of Excellence in Phytomedicine Research and Development, University of Jos, Jos, Nigeria; Department of Pharmaceutical and Medicinal Chemistry, University of Jos, Jos, Nigeria. , (Niger)
  • 6 Department of Pharmacology and Toxicology, University of Jos, Jos, Nigeria. , (Niger)
Type
Published Article
Journal
Annales Pharmaceutiques Françaises
Publisher
Elsevier
Publication Date
Nov 01, 2022
Volume
80
Issue
6
Pages
864–875
Identifiers
DOI: 10.1016/j.pharma.2022.02.006
PMID: 35231396
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lamivudine and tenofovir disoproxil fumarate act against the replication of hepatitis B and human immunodeficiency viruses via inhibition of the reverse transcriptase enzyme activity, thereby preventing the synthesis of viral DNA. Chronic administration of these drugs has been associated with toxicities, including senescence, oxidative stress and premature death. A study of these toxicities in Drosophila melanogaster, which share 75% genomic similarity with humans could help to develop a pharmacologic intervention. Susceptibility of D. melanogaster for lamivudine and tenofovir-induced toxicities were investigated. First, flies (≤3 days old) were fed with drugs-supplemented diet at varying concentrations (1mg to 300mg/10-gram diet) or distilled water for seven days to determine LD50. Secondly, five groups of 60 flies were fed with four concentrations of test drugs: 2.9mg, 5.82mg, 11.64mg and 23.28mg each per 10-gram diet for 28 days survival and lifespan assays. Then 5-day treatment plan was utilized to determine drugs toxicities on climbing ability and some biomarkers of oxidative stress. Finally, molecular docking was carried out using the Auto-dock vina mode to predict the biological interactions between the test drugs and D. melanogaster acetylcholinesterase (AChE) or glutathione-S-transferase (GST). The LD50 of lamivudine or tenofovir was 47.07 or 43.95mg/10g diet, respectively. Each drug significantly (P<0.05) reduced the survival rate, longevity and climbing performance of the flies dose-dependently. These drugs also altered levels of biochemical parameters: AChE, GST, superoxide dismutase (SOD), catalase (CAT), total thiol (T-SH), and malondialdehyde (MDA) of the flies significantly (P<0.05). In silico molecular analysis showed that the test drugs interacted with significantly (P<0.05) higher binding affinities at the same catalytic sites of D. melanogaster GST and AChE compared with substrates (glutathione or acetylcholine). The significant lamivudine and tenofovir-induced toxicities observed as increased mortality, climbing deficits and compromised antioxidant defence in D. melanogaster demands further research for possible pharmacological intervention. Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Report this publication

Statistics

Seen <100 times