DNA polymerase-γ hypothesis in nucleoside reverse transcriptase-induced mitochondrial toxicity revisited: A...

Area of Science:

• Biochemistry
• Pharmacology
• Toxicology

Background:

• Nucleoside reverse transcriptase inhibitors (NRTIs) are crucial in combination antiretroviral therapy (cARVs) for HIV treatment.
• NRTIs can inhibit both viral and human DNA polymerases, including mitochondrial DNA polymerase-γ, leading to mitochondrial toxicity.
• Clinical manifestations of NRTI-induced mitochondrial toxicity include myopathy, neuropathy, and metabolic disturbances.

Purpose of the Study:

• To review the mechanisms of NRTI-induced mitochondrial toxicity, focusing on the role of mitochondrial DNA polymerase-γ and oxidative stress.
• To evaluate the potential of naringenin, a citrus-derived flavonoid, as a therapeutic agent to mitigate NRTI-induced mitochondrial toxicity.

Main Methods:

• Literature review of studies on NRTI mechanisms, mitochondrial toxicity, oxidative stress, and naringenin's properties.
• Analysis of existing hypotheses regarding NRTI-induced mitochondrial damage.
• Evaluation of naringenin's antioxidant and free radical scavenging capabilities.

Main Results:

• NRTIs impair mitochondrial DNA polymerase-γ, contributing to toxicity, with oxidative stress also implicated in metabolic complications.
• Previous attempts at clinical intervention with antioxidants have shown limited success.
• Naringenin exhibits significant antioxidant and free radical scavenging properties.

Conclusions:

• Naringenin shows promise as a nutritional supplement or therapeutic adjunct to prevent or reduce NRTI-induced mitochondrial toxicity.
• Further research is warranted to explore naringenin's efficacy and optimal use in managing NRTI-related side effects.
• Understanding the interplay between mtDNA polymerase-γ inhibition and oxidative stress is key to developing effective interventions.