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

Iorjiim, Walter Mdekera; Omale, Simeon; Etuh, Monday Alexander; Ubani, Amaka; Alemika, Taiwo E.; Gyang, Steven Samuel

doi:10.1016/j.pharma.2022.02.006

Cited by 5 publications

(5 citation statements)

References 31 publications

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“…The interaction of DTG with TYR A:208 was through an H-bond interaction, which could form a stable ligand-enzyme complex 34 . This observation in the current study agrees with the previous findings of Iorjiim et al 43 and Johnson et al 34 where in silico ligands and Drosophila GST interaction via the amino acid TYR A: 208 reduced the activity of the enzyme.…”

Section: Discussionsupporting

confidence: 94%

“…The increased MDA result in the current investigation agrees with that of Adaramoye et al 45 , who reported a significant increase in MDA levels after four weeks of exposure to nevirapine or tenofovir in Wistar rats 46 . Similarly, in the previous investigation 43 , lamivudine or tenofovir disoproxil fumarate significantly impaired antioxidant capacity in fruit flies. The altered antioxidant biomarkers in the current study (T-SH, GST, SOD and CAT) (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…7a-c). An interaction between AChE with other antiretroviral drugs such as lamivudine and tenofovir disoproxil fumarate that revealed toxic potentials both in silico and in vivo has been reported by Iorjiim et al 43 . However, in this study, the in silico result revealed a weak interaction between DTG and AChE (Fig.…”

Section: Discussionmentioning

confidence: 72%

“…Huperzine-A is a plant antioxidant from Huperzia serrata 41 , therefore, its fertility-enhancing activity could be driven by the antioxidant property of the compound as reported by Agarwal et al 42 and not an AChE inhibitory effect. This result indicated that DTG induced no noticeable reproductive toxicity against fruit flies, unlike lamivudine and tenofovir disoproxil fumarate, which significantly (p<0.05) impaired both AChE activity and reproductive capacity after oral exposure in the study of Iorjiim et al 43 .…”

Section: Discussionmentioning

confidence: 79%

“…Also, Oyeyipo et al 50 found a significant reduction of these enzymes in ratʼs testicles exposed to EFV-containing HAART 50 . Similarly, lamivudine or tenofovir significantly decreased CAT and SOD activities in D. melanogaster 43 .…”

Section: Discussionmentioning

confidence: 88%

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Dolutegravir Increased Mortality Rate, Climbing Deficits and Altered Biomarkers of Oxidative Injury in Harwich Drosophila melanogaster

Iorjiim¹,

Omale²,

Bagu³

et al. 2023

J. of Pharmacology and Toxicology

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Background and Objective: Dolutegravir (DTG) is safer compared to Efavirenz (EFV) as a component of antiretroviral combination therapy.However, recent studies suggested that DTG might be associated with oxidative stress toxicity in humans. This study intended to assess whether a non-target organism, Drosophila melanogaster, could replicate the DTG-induced oxidative stress and to determine the potential toxicity of a finished dolutegravir product because of possible environmental contamination. Materials and Methods: Flies (mixed sexes) were exposed to a series of ten DTG concentrations (0-50 mg per 10 g fly food) for a 7 days LD 50 determination, followed by a 28 days survival assay, then a 5 days treatment to evaluate the effects of the test drug on negative geotaxis, fertility and some antioxidant biomarkers. Also, in silico molecular docking was performed to predict the possible molecular interactions of Drosophila acetylcholinesterase (AChE) and glutathione-S-transferase (GST) enzymes with the test drug. Results: The LD 50 of DTG in D. melanogaster was 16.53 mg/10 g of food. The DTG showed a significant (p<0.05) reduction in 28 days survival and climbing ability as well as alterations in the levels of biochemical markers [total thiols (T-SH), AChE, GST, catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA)] of the exposed flies. The test drug interacted with similar amino acid residues with a significantly (p<0.05) higher molecular attraction for the active sites of GST but a lower (p>0.05) binding affinity for those of AChE compared to the respective natural substrates and standard inhibitors. Conclusion: Oral administration of DTG in D. melanogaster significantly increased mortality rate, climbing and antioxidant deficits through a competitive antagonism of GST and AChE activities. The DTG-induced oxidative stress was replicated in the flies. Thus, environmental contamination with dolutegravir sodium could adversely affect non-target organisms in an ecosystem.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 88%

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Dolutegravir Increased Mortality Rate, Climbing Deficits and Altered Biomarkers of Oxidative Injury in Harwich Drosophila melanogaster

Iorjiim¹,

Omale²,

Bagu³

et al. 2023

J. of Pharmacology and Toxicology

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

Iorjiim,

Omale,

Ede

et al. 2023

Toxicology Research

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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.

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Factors Associated with Periodontitis in Patients with and without HIV

Pereira

Amorim

Sampaio

et al. 2023

International Journal of Dentistry

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Purpose. The aim of this study was to compare clinical periodontal conditions in HIV-positive people on HAART with an HIV-negative group, in addition to investigating factors associated with periodontitis in the entire sample. Methods. This was a cross-sectional study. Data were collected by oral clinical examination for the diagnosis of periodontitis, review of medical records, and application of a questionnaire containing personal data, deleterious habits, and oral hygiene habits for the other variables. The results were analyzed by Pearson’s χ2 test and Student’s t-test. A logistic regression model was constructed for the multivariate analysis and periodontitis was defined as a dependent variable. The analysis was performed on the entire sample (HIV+ and HIV−) and also on the group consisting of only people living with HIV. Results. Individuals older than 43 years old and with HIV were more likely to develop moderate and severe periodontitis (47.80 and 4.84 times, respectively). When analyzing only HIV+, in addition to age (OR = 2.795; CI = 1.080−7.233), the use of nonnucleoside reverse transcriptase inhibitors (NNRTIs) (OR = 2.841; CI = 1.135−7.112) was also associated with moderate and severe periodontitis. Conclusion. It was possible to observe a higher prevalence of periodontitis among individuals with HIV, showing an association between the virus, advanced age, and moderate or severe periodontitis.

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

Cited by 5 publications

References 31 publications

Dolutegravir Increased Mortality Rate, Climbing Deficits and Altered Biomarkers of Oxidative Injury in Harwich Drosophila melanogaster

Dolutegravir Increased Mortality Rate, Climbing Deficits and Altered Biomarkers of Oxidative Injury in Harwich Drosophila melanogaster

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

Factors Associated with Periodontitis in Patients with and without HIV

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