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Oxidative stress in NRTI-induced toxicity

Evidence from clinical experience and experiments in vitro and in vivo

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Abstract

This article reviews the relationship of oxidative stress with nucleoside reverse transcriptase inhibitor (NRTI)-induced toxicity and suggests how oxidative stress may participate in NRT1-mediated toxicity. NRTIs are pro-drugs that require intracellular phosphorylation to their 5′ triphophates by cellular kinases to inhibit viral and mitochondrial DNA (mtDNA) replication. NRTIs in highly active antiretroviral therapy have decreased morbidity and mortality, but side effects can be limiting after prolonged use. These side effects may be linked through mitochondrial dyfunction arising from altered mtDNA replication and oxidative stress via destruction of elements of mtDNA replication, decreased oxidative phosphorylation, and cellular function. Although oxidative stress is associated with NRTI therapy, there is still debate about whether it plays a direct role in NRTI-induced toxicity. The impact of oxidative stress on cardiovascular disease is likely to increase, because patients with HIV infection are living longer as a result of effective antiretroviral therapy.

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  1. Department of Medicine, K715, National Jewish Medical & Research Center, 1400 Jackson St., 80206, Denver, CO

    Brian J. Day PhD

  2. Department of Medicine, University of Colorado Health Sciences Center, Denver, CO

    Brian J. Day PhD

  3. Department of Pharmaceutical Science, University of Colorado Health Sciences Center, Denver, CO

    Brian J. Day PhD

  4. Department of Pathology, Emyory University School of Medicine, Atlanta, GA

    William Lewis

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Day, B.J., Lewis, W. Oxidative stress in NRTI-induced toxicity. Cardiovasc Toxicol 4, 207–216 (2004). https://doi.org/10.1385/CT:4:3:207

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