Coenzyme Q10 Alleviates Chronic Nucleoside Reverse Transcriptase Inhibitor-Induced Premature Endothelial Senescence
Open accessAbstract
Human immunodeficiency virus (HIV)-infected patients undergoing antiretroviral therapy are afforded an increased lifespan but also exhibit an elevated incidence of cardiovascular disease. HIV therapy uses a combination drug approach, and nucleoside reverse transcriptase inhibitors (NRTI) are a backbone of this therapy. Endothelial dysfunction is an initiating event in cardiovascular disease etiology, and in our prior studies, NRTIs induced an endothelial dysfunction that was dependent upon mitochondrial oxidative stress. Moreover, short-term NRTI administration induced a mitophagy-associated endothelial toxicity and increased reactive oxygen species (ROS) production that was rescued by coenzyme Q10 (Q10) or overexpression of a mitochondrial antioxidant enzyme. Thus, our objective was to examine mitochondrial toxicity in endothelial cells after chronic NRTI treatment and evaluate Q10 as a potential adjunct therapy for preventing NRTI-induced mitochondrial toxicity. Human aortic endothelial cells (HAEC) were exposed to chronic NRTI treatment, with or without Q10. ROS production, cell proliferation rate, levels of senescence, and mitochondrial bioenergetic function were determined. Chronic NRTI increased ROS production but decreased population doubling. In addition, NRTI increased the accumulation of β-galactosidase, indicative of an accelerated rate of senescence. Moreover, ATP-linked respiration was diminished. Co-treatment with Q10 delayed the onset of NRTI-induced senescence, decreased ROS production and rescued the cells' mitochondrial respiration rate. Thus, our findings may suggest antioxidant enrichment approaches for reducing the cardiovascular side effects of NRTI therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Coenzyme Q10, SkQ1, mitoquinone and methylene blue are among mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied.
“Coenzyme Q10 (CoQ10), SkQ1 (a.k.a. visomitin), mitoquinone (MitoQ) and methylene blue are among the mitochondria targeted antioxidants exerting a role in counteracting OS-induced senescence, with CoQ10 being the most studied (Table 1 and Table 2) [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [59]
CoQ10 supplementation reverts in vitro the NRTI-induced oxidative damage, senescence, and endothelial toxicity phenotype in human aortic endothelial cells.
“Recently, Chen et al. demonstrated that this phenotype could be reverted in vitro when human aortic endothelial cells are supplemented with CoQ10 [59]”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [59]
Cites
The clinical implications of endothelial dysfunction
Widlansky, M. E., Gokce, N., Keaney, J. F., & Vita, J. A. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00994-x · Cited by 1,749 · see citing works
Role of PFKFB3-Driven Glycolysis in Vessel Sprouting
Bock, K. D., Γεωργιάδου, Μ., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., Quaegebeur, A., Ghesquière, B., Cauwenberghs, S., Eelen, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.037 · Cited by 1,559 · see citing works
HIV Infection and the Risk of Acute Myocardial Infarction
Freiberg, M. S., Chang, C.-C. H., Kuller, L. H., Skanderson, M., Lowy, E., Kraemer, K. L., Butt, A. A., Goetz, M. B., Leaf, D. A., Oursler, K. A., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.3728 · Cited by 1,340 · see citing works
Biochemical, physiological and medical aspects of ubiquinone function
Ernster, L., & Dallner, G. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/0925-4439(95)00028-3 · Cited by 1,227 · see citing works
Wu, M., Neilson, A., Swift, A. L., Moran, R., Tamagnine, J., Parslow, D., Armistead, S., Lemire, K., Orrell, J., Teich, J., et al. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00247.2006 · Cited by 922 · see citing works
Cristofalo, V. J., Allen, R. G., Pignolo, R. J., Martin, B. G., & Beck, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10614 · Cited by 554 · see citing works
Kurz, D. J., Decary, S., Hong, Y., Trivier, E., Akhmedov, A., & Erusalimsky, J. D. (2004) · Journal of Cell Science · doi:10.1242/jcs.01097 · Cited by 499 · see citing works
Integration of cellular bioenergetics with mitochondrial quality control and autophagy
Hill, B. G., Benavides, G. A., Lancaster, J. R., Ballinger, S. W., Dell’Italia, L., Zhang, J., & Darley-Usmar, V. M. (2012) · Biological Chemistry · doi:10.1515/hsz-2012-0198 · Cited by 481 · see citing works
Oxidative stress and aberrant signaling in aging and cognitive decline
Dröge, W., & Schipper, H. M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00294.x · Cited by 479 · see citing works
Assessing bioenergetic function in response to oxidative stress by metabolic profiling
Dranka, B. P., Benavides, G. A., Diers, A. R., Giordano, S., Zelickson, B. R., Reily, C., Zou, L., Chatham, J. C., Hill, B. G., Zhang, J., et al. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.08.005 · Cited by 436 · see citing works
Mitochondria and Cardiovascular Aging
Dai, D., Rabinovitch, P. S., & Ungvari, Z. I. (2012) · Circulation Research · doi:10.1161/circresaha.111.246140 · Cited by 435 · see citing works
Islam, F., Wu, J., Jansson, J., & Wilson, D. (2012) · HIV Medicine · doi:10.1111/j.1468-1293.2012.00996.x · Cited by 432 · see citing works
The contributions of respiration and glycolysis to extracellular acid production
Mookerjee, S. A., Goncalves, R. L. S., Gerencser, A. A., Nicholls, D. G., & Brand, M. D. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.10.005 · Cited by 347 · see citing works
Nolan, D. A., Hammond, E., Martin, A. M., Taylor, L., Herrmann, S., McKinnon, E., Metcalf, C., Latham, B. I., & Mallal, S. A. (2003) · AIDS · doi:10.1097/00002030-200306130-00007 · Cited by 265 · see citing works
Regulation of mitochondrial oxidative phosphorylation through cell signaling
Hüttemann, M., Lee, I., Samavati, L., Yu, H., & Doan, J. W. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.10.001 · Cited by 265 · see citing works
An analysis of the role of coenzyme Q in free radical generation and as an antioxidant
Beyer, R. E. (1992) · Biochemistry and Cell Biology · doi:10.1139/o92-061 · Cited by 250 · see citing works
Pamukcu, B., Lip, G. Y. H., & Shantsila, E. (2011) · Thrombosis Research · doi:10.1016/j.thromres.2011.03.025 · Cited by 218 · see citing works
Mechanisms linking mtDNA damage and aging
Pinto, M., & Moraes, C. T. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.05.005 · Cited by 179 · see citing works
Mitochondrial respiratory chain super-complex I–III in physiology and pathology
Lenaz, G., Baracca, A., Barbero, G., Bergamini, C., Dalmonte, M. E., Sole, M. D., Faccioli, M., Falasca, A. I., Fato, R., Genova, M. L., et al. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.025 · Cited by 120 · see citing works
Caron, M., Auclair, M., Vissian, A., Vigouroux, C., & Capeau, J. (2008) · Antiviral Therapy · doi:10.1177/135965350801300103 · Cited by 114 · see citing works
Premature senescence of human endothelial cells induced by inhibition of glutaminase
Unterluggauer, H., Mazurek, S., Lener, B., Hütter, E., EIGENBRODT, E., Zwerschke, W., & Jansen‐Dürr, P. (2008) · Biogerontology · doi:10.1007/s10522-008-9134-x · Cited by 107 · see citing works
McCarthy, C., & Kenny, L. C. (2016) · Scientific Reports · doi:10.1038/srep32683 · Cited by 100 · see citing works
Kline, E. R., & Sutliff, R. L. (2008) · Journal of Investigative Medicine · doi:10.1097/jim.0b013e3181788d15 · Cited by 93 · see citing works
JIANG, B., Hebert, V. Y., Li, Y., Mathis, J. M., Alexander, J. S., & Dugas, T. R. (2007) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2007.06.010 · Cited by 85 · see citing works
Self-citationAbsence of a Universal Mechanism of Mitochondrial Toxicity by Nucleoside Analogs
Lund, K. C., Peterson, L., & Wallace, K. B. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00039-07 · Cited by 77 · see citing works
Wang, L. H., Chittick, G. E., & McDowell, J. A. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.7.1708 · Cited by 65 · see citing works
Antiretrovirals Induce Direct Endothelial Dysfunction In Vivo
Jiang, B., Hebert, V. Y., Zavecz, J. H., & Dugas, T. R. (2006) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000228790.40235.0c · Cited by 64 · see citing works
Self-citationMitochondrial stress induces cellular senescence in an mTORC1-dependent manner
Nacarelli, T., Azar, A., & Sell, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.008 · Cited by 58 · see citing works
Effects of HIV Drug Combinations on Endothelin-1 and Vascular Cell Proliferation
Hebert, V. Y., Crenshaw, B. L., Romanoff, R. L., Ekshyyan, V., & Dugas, T. R. (2004) · Cardiovascular Toxicology · doi:10.1385/ct:4:2:117 · Cited by 57 · see citing works
Self-citationClay, A. S., Behnia, M. M., & Brown, K. M. (2001) · CHEST Journal · doi:10.1378/chest.120.2.634 · Cited by 56 · see citing works
Kline, E. R., Bassit, L., Hernández-Santiago, B. I., Detorio, M., Liang, B., Kleinhenz, D. J., Walp, E. R., Dikalov, S., Jones, D. P., Schinazi, R. F., et al. (2008) · Cardiovascular Toxicology · doi:10.1007/s12012-008-9029-8 · Cited by 55 · see citing works
McComsey, G. A., Bai, R., Maa, J., Seekins, D. W., & Wong, L. (2005) · PubMed · Cited by 51 · see citing works
Jiang, B., Khandelwal, A. R., Rogers, L. K., Hebert, V. Y., Kleinedler, J. J., Zavecz, J. H., Shi, W., Orr, A. W., & Dugas, T. R. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq213 · Cited by 37 · see citing works
Self-citationGlover, M. C., Hebert, V. Y., Nichols, K., Xue, S. Y., Thibeaux, T. M., Zavecz, J. H., & Dugas, T. R. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.09.010 · Cited by 33 · see citing works
Self-citationXue, S. Y., Hebert, V. Y., Hayes, D. M., Robinson, C. N., Glover, M. C., & Dugas, T. R. (2013) · Toxicological Sciences · doi:10.1093/toxsci/kft105 · Cited by 26 · see citing works
Self-citationCanadian multicenter azidothymidine trial: AZT pharmacokinetics.
Child, S., Montaner, J. S. G., Tsoukas, C. M., Fanning, M. M., Le, T., Wall, R. A., & Ruedy, J. (1991) · PubMed · Cited by 22 · see citing works
Wang, H., Zhou, J., He, Q., Dong, Y., & Liu, Y. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6549 · Cited by 21 · see citing works
Cressey, T. R., Avihingsanon, A., Halue, G., Leenasirimakul, P., Sukrakanchana, P.-O., Tawon, Y., Jaisieng, N., Jourdain, G., Podany, A. T., Fletcher, C. V., et al. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ346 · Cited by 18 · see citing works
Canadian Multicenter Azidothymidine Trial
Child, S., Montaner, J., Tsoukas, C. M., Fanning, M. M., Le, T. N., Wall, R. A., & Ruedy, J. R. (1991) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-199109000-00007 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing
Ajoolabady, A., Aslkhodapasandhokmabad, H., Aghanejad, A., Zhang, Y., & Ren, J. T. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101129 · Cited by 103 · see citing works
The struggle of a good friend getting old: cellular senescence in viral responses and therapy
Kohli, J., Veenstra, I., & Demaria, M. (2021) · The EMBO Reports · doi:10.15252/embr.202052243 · Cited by 52 · see citing works
Human Immunodeficiency Virus as a Risk Factor for Cardiovascular Disease
Lembas, A., Załęski, A., Peller, M., Mikuła, T., & Wiercińska‐Drapało, A. (2023) · Cardiovascular Toxicology · doi:10.1007/s12012-023-09815-4 · Cited by 27 · see citing works
Coenzyme Q homeostasis in aging: Response to non-genetic interventions
López‐Lluch, G. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.01.024 · Cited by 28 · see citing works
Guo, M., & Buch, S. J. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146446 · Cited by 19 · see citing works
Chen, Y.-F., & Dugas, T. R. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.09.018 · Cited by 16 · see citing works
Self-citationEmerging roles of senolytics/senomorphics in HIV-related co-morbidities
Kaur, G., Rahman, M. S., Shaikh, S. B., Panda, K., Chinnapaiyan, S., Estevez, M. S., Xia, L., Unwalla, H. J., & Rahman, I. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116179 · Cited by 6 · see citing works
Quercetin from edible Rutaceae plants: phytochemical profiling and therapeutic applications
Ghosh, S., Debnath, I., & Saha, P. (2025) · Prospects in Pharmaceutical Sciences · doi:10.56782/pps.581 · Cited by 3 · see citing works
Introductory background to telomere shortening
Mantle, D. (2025) · Journal of Kidney Care · doi:10.12968/jokc.2025.0013
- Authors
- Chen, Y.-F., Hebert, V. Y., Stadler, K., Xue, S. Y., Slaybaugh, K., Luttrell-Williams, E., Glover, M. C., Krzywanski, D. M., & Dugas, T. R.
- Affiliations
- Louisiana State University Health Sciences Center Shreveport (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Louisiana State University (US)
- Corresponding author
- Dugas, Tammy R.
- Venue
- Cardiovascular Toxicology
- Published
- 2019-04-24
- Volume
- 19
- Issue
- 6
- Pages
- 500-509
- ISSN
- 1530-7905 (ISSN-L)
- 1559-0259
- OpenAlex
- W2941212302
- Cited by
- 10
- References
- 39
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cardiovascular Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- School of Veterinary Medicine, Louisiana State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- coenzyme Q10, nucleoside reverse transcriptase inhibitors, endothelial cell senescence, mitochondrial toxicity, oxidative stress, reactive oxygen species, endothelial dysfunction, mitochondrial respiration, HIV, antioxidant therapy, beta-galactosidase, ATP-linked respiration, mitophagy
- MeSH terms
- Antioxidants, Cells, Cultured, Energy Metabolism, Humans, Mitochondria, Ubiquinone, Signal Transduction, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, Reverse Transcriptase Inhibitors, Cytoprotection, Endothelial Cells, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
