Absence of effect of the antiretrovirals Duovir and Viraday on mitochondrial bioenergetics.

Abstract

Most toxicity associated with antiretroviral drugs is thought to result from disruption of mitochondrial function. Unfortunately, there are no validated laboratory markers for clinically assessing the onset of mitochondrial toxicity associated with antiretroviral therapy. In a previous study on mitochondrial hepatocytes, the protease inhibitor lopimune was shown to induce mitochondrial toxicity by increasing reactive oxygen species (ROS) production and decreasing respiratory control ratio (RCR) reflecting compromised mitochondrial efficiency in adenosine triphosphate production. Mitochondrial dysfunction and ROS production were directly correlated with the expression of uncoupling protein 2 (UCP2). In the current study we aim to determine the toxicity of nucleoside or nucleotide and nonnucleoside reverse-transcriptase inhibitors, Duovir and Viraday on liver mitochondria isolated from treated mice by monitoring UCP2 expression. Our results showed that both Duovir and Viraday had no effect on mitochondrial respiration states 2, 3, 4, and on RCR. In addition, ROS generation and UCP2 expression were not affected. In conclusion, our results indicate the difference in the mechanism of action of distinct classes of antiretroviral drugs on mitochondrial functions and may associate UCP2 expression with subclinical mitochondrial damage as marker of cellular oxidative stress.

• Authors: Jessy J Fadel, Georges M Bahr, Karim S Echtay
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 12 Pg. 10384-10392 (12 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 30187948 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Anti-Retroviral Agents
• Drug Combinations
• Ion Channels
• Mitochondrial Proteins
• Reactive Oxygen Species
• lopinavir-ritonavir drug combination
• Lopinavir
• Adenosine Triphosphate
• Ritonavir

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Anti-Retroviral Agents (administration & dosage)
• Drug Combinations
• Energy Metabolism
• HIV Infections (drug therapy, pathology, virology)
• Hepatocytes (drug effects, virology)
• Ion Channels (drug effects)
• Lopinavir (administration & dosage)
• Mice
• Mitochondria (drug effects)
• Mitochondria, Liver (drug effects, virology)
• Mitochondrial Proteins (genetics)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)
• Ritonavir (administration & dosage)