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Title: Absence of effect of the antiretrovirals duovir and viraday on mitochondrial bioenergetics
Authors: Fadel, Jessy
Bahr, George M. 
Echtay, Karim 
Affiliations: Faculty of Medicine 
Faculty of Medicine 
Keywords: Antiretroviral
Nonnucleoside reverse-transcriptase inhibitor
Nucleoside ornucleotide reverse-transcriptase inhibitor
Nucleotide reversetranscriptaseinhibitors
Respiratory control ratio
Reactive oxygen species
Uncoupling protein 2
Subjects: Mitochondria
Issue Date: 2018
Part of: Journal of cellar biochemistry
Volume: 119
Issue: 12
Start page: 10384
End page: 10392
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.
DOI: 10.1002/jcb.27384
Ezproxy URL: Link to full text
Type: Journal Article
Appears in Collections:Faculty of Medicine

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