Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.

ABSTRACT: Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of first generation NRTIs, which are rarely discussed in the literature, include inhibition of oxygen consumption

SUBMITTER: Smith RL 

PROVIDER: S-EPMC5667870 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature