Important note: Information in this article was accurate in December 2001. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, December 3, 2001
Michael Greer, Senior Medical Writer
NewsRx -- Researchers in the United States and Italy have devised a novel method for measuring mitochondrial toxicity caused by antiretroviral HIV drugs.
"Mitochondrial toxicity is a serious side effect of antiretroviral drugs, especially nucleoside reverse transcriptase inhibitors (NRTI)," explained Andrea Foli and colleagues at the Research Institute for Genetic and Human Therapy, based in Pavia, Italy, and Washington DC, IRCSS Policlinico San Matteo in Pavia, and the University of Modena in Modena, Italy. "An in vitro assay to predict mitochondrial toxicity of in-use and developmental NRTI would be invaluable."
Foli and coworkers have developed just such an assay, using cellular fluorometry to quantify mitochondrial damage, according to their report.
Changes in the mitochondrial membrane due to toxicity enables entry by the lipophilic cation JC-1, they said. This entry changes the color of mitochondria, and this discoloration can be precisely measured with cytofluorometric techniques.
The researchers used their assay to test the pancreatic and hepatic toxicity of the NRTI didanosine (ddI) and the DNA synthesis inhibitor hydroxyurea (HU). Significant and dose-dependent damage to pancreatic cell mitochondria was seen after two weeks in culture with ddI, study data showed. Moreover, while HU alone had no adverse effect on pancreatic cells, it exacerbated ddI-induced damage when the NRTI was present at high levels. These results were consistent with in vivo data on ddI and HU toxicity, Foli and team noted.
Neither ddI alone nor the combination of ddI and hydroxyurea had any toxic effect on hepatic mitochondria, which was also consistent with in vivo data (Direct analysis of mitochondrial toxicity of antiretroviral drugs, AIDS 2001 Sep 7;15(13):1687-94.
"The in vitro assay described here might be used to predict the mitochondrial toxicity of other NRTI, alone or in combination," Foli and coauthors concluded.
The corresponding author for this report is Franco Lori, IRCCS Policlinico San Matteo, Research Institute for Genetic and Human Therapy (RIGHT), I-27100 Pavia, Italy.
A search at www.NewsRx.net using the term "AIDS and HIV therapy" yielded 872 articles in 20 specialized reports.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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