Zidovudine Phosphorylation and Mitochondrial Toxicity in Vitro

• Published in: Toxicology and applied pharmacology Vol. 177; no. 1; pp. 54 - 58
• Main Authors: Sales, S.D., Hoggard, P.G., Sunderland, D., Khoo, S., Hart, C.A., Back, D.J.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.11.2001; Elsevier
• Subjects: Biological and medical sciences; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Humans; In Vitro Techniques; intracellular phosphorylation; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Lymphocytes - drug effects; Lymphocytes - metabolism; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial toxicity; Monocytes - drug effects; Monocytes - metabolism; Pharmacology. Drug treatments; Phosphorylation; Phytohemagglutinins - pharmacology; Succinate Dehydrogenase - metabolism; Thymidine Kinase - metabolism; U937 Cells - cytology; U937 Cells - drug effects; U937 Cells - metabolism; Zidovudine; Zidovudine - metabolism; Zidovudine - toxicity; Zidovudine; intracellular phosphorylation; mitochondrial toxicity; Human; Cell culture; Mitochondria; Phosphorylation; Metabolite; Toxicity; Dideoxynucleoside; Metabolism toxicity relation; Antiviral; In vitro; Pyrimidine nucleoside

Zidovudine (ZDV) is a thymidine analogue activated to its triphosphate (ZDVTP) by the host's intracellular enzymes. The initial phosphorylation step is conversion to ZDV monophosphate (ZDVMP). The poor affinity of ZDVMP for thymidylate kinase results in intracellular accumulation of ZDVMP. Clin...