Nucleoside Analogues and Mitochondrial Toxicity

Nucleoside analogues and mitochondrial toxicity.

An evaluation of the US Food and Drug Administration's Adverse Event Reporting System identified that patients coinfected with human immunodeficiency virus and chronic hepatitis C virus who were treated with a regimen of ribavirin and didanosine, with or without stavudine, were at increased risk for events associated with mitochondrial toxicity, including fatal hepatic failure, peripheral neuro...

Nucleoside Analogues and Mitochondrial Toxicity

Infectious Diseases Unit, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Received for publication: January 17, 2006. Reprint request: Ubonvan Jongwutiwes, M.D., Infectious Diseases Unit, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. E-mail: [email protected]

Mitochondrial toxicity of nucleoside analogues in primary human lymphocytes.

OBJECTIVE To evaluate if nucleoside analogue reverse transcriptase inhibitors (NRTIs) and polymerase-gamma inhibitors deplete mitochondrial DNA (mtDNA) in cultured primary lymphocytes and if such depletion might be associated with functional defects. METHODS Primary peripheral blood CD4 and CD8 lymphocytes were purified from six healthy humans (three male and three female), stimulated mitotic...

Chemical Synthesis of Nucleoside Analogues Chemical Synthesis of Nucleoside Analogues

NUCLEOSIDE ANALOG TOXICITY AND NUCLEOSIDE KINASE DEFICIENCY; effects on mitochondrial DNA

Nucleoside analogs are modified nucleosides used in treatment of cancer and viral infections. They are dependent on intracellular phosphorylation to be pharmacologically active. Deoxyribonucleoside kinases catalyze the rate-limiting step in the phosphorylation of many clinically used nucleoside analogs. Human cells contain four distinct deoxyribonucleoside kinases that have partially overlappin...