DNA polymerase-γ hypothesis in nucleoside reverse transcriptase-induced mitochondrial toxicity revisited: A potentially protective role for citrus fruit-derived naringenin?
Level 5 - mechanism / opinion, no new human data
Narrative review and mechanistic hypothesis without new empirical clinical data
PubMed 30876974 · doi:10.1016/j.ejphar.2019.03.017
What was done
This narrative review examined the mechanistic basis of nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity—focusing on DNA polymerase-γ inhibition and oxidative stress—and evaluated the potential protective role of citrus fruit-derived naringenin as an antioxidant and therapeutic adjunct.
What was found
The abstract reports no quantitative experimental or clinical data. It outlines known mechanisms of NRTI toxicity (inhibition of viral and mitochondrial DNA polymerases leading to myopathy, neuropathy, lactic acidosis, and lipoatrophy) and notes that prior antioxidant trials have had limited success. It summarizes the theoretical rationale for naringenin's antioxidant and free-radical-scavenging properties.
Why it matters
It highlights oxidative stress pathways in antiretroviral-related metabolic complications and outlines a biochemical rationale for testing citrus bioflavonoids as supportive adjuncts.
Limits
As a conceptual review, no new empirical human or animal data are presented in the abstract. Clinical efficacy, safety, optimal dosing, and pharmacokinetic interactions between naringenin and antiretroviral regimens remain untested in formal clinical trials.
Cited by
- supports Certain HIV therapeutics impair mitochondrial function.