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Citations to this article

Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy.
T M Sinnwell, … , A C McLaughlin, M C Dalakas
T M Sinnwell, … , A C McLaughlin, M C Dalakas
Published July 1, 1995
Citation Information: J Clin Invest. 1995;96(1):126-131. https://doi.org/10.1172/JCI118012.
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Research Article

Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy.

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Abstract

Patients on long-term zidovudine (AZT) therapy experience muscle fatigue and weakness attributed to AZT-induced mitochondrial toxicity in skeletal muscle. To determine if the clinico-pathological abnormalities in these patients correspond to abnormal muscle energy metabolism, we used 31P in vivo magnetic resonance spectroscopy to follow phosphorylated metabolites during exercise. We studied 19 normal volunteers, 6 HIV-positive patients never treated with AZT, and 9 HIV-positive patients who had been treated with AZT for a mean period of 33 mo (range 12-48 mo) and had muscle biopsy-proven AZT-myopathy with abnormal mitochondria. Changes in phosphocreatine, ATP, and intracellular pH in the gastrocnemius muscle were followed during a graded steady state exercise protocol, and the recovery of phosphocreatine was followed on cessation of exercise. We found that graded steady state exercise produced a greater depletion of muscle phosphocreatine levels in the AZT-treated patients, compared to either HIV-positive patients who were not treated with AZT or normal controls. No differences in the effects of steady state exercise on muscle phosphocreatine levels were observed between the control group and the HIV-positive patients who had not been treated with AZT. The results suggest that the effect of AZT on muscle energy metabolism is significant, and similar to the effect observed in patients with known mitochondrial myopathies. Using a well-known model for control of mitochondrial metabolism, the observed differences in steady state phosphocreatine levels during exercise suggest that AZT treatment decreases the maximal work output and the maximal rate of muscle ATP synthesis.

Authors

T M Sinnwell, K Sivakumar, S Soueidan, C Jay, J A Frank, A C McLaughlin, M C Dalakas

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Total citations by year

Year: 2019 2016 2014 2013 2011 2010 2009 2008 2007 2006 2004 2003 2002 2001 2000 1999 1998 1997 Total
Citations: 1 2 2 1 1 1 2 1 3 2 2 5 3 1 4 2 1 3 37
Citation information
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Citations to this article (37)

Title and authors Publication Year
Muscle Toxicity of Drugs: When Medication Turns Physiology into Pathophysiology
L Janssen, N Allard, C Saris, J Keijer, MT Hopman, S Timmers
Physiological reviews 2019
Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial
H Makimura, TL Stanley, C Suresh, AL de Sousa-Coelho, WR Frontera, S Syu, LR Braun, SE Looby, MN Feldpausch, M Torriani, H Lee, ME Patti, SK Grinspoon
The Journal of clinical endocrinology and metabolism 2016
Skeletal muscle cellular metabolism in older HIV‐infected men
HK Ortmeyer, AS Ryan, C HaferMacko, KA Oursler
Physiological Reports 2016
Heteronuclear complexes of phosphocreatine with copper(II) and magnesium(II) ions
R Jastrzab, M Nowak, M Zabiszak
Journal of the Iranian Chemical Society 2014
In Vivo Mitochondrial Function in HIV-Infected Persons Treated with Contemporary Anti-Retroviral Therapy: A Magnetic Resonance Spectroscopy Study
BA Payne, KG Hollingsworth, J Baxter, E Wilkins, V Lee, DA Price, M Trenell, PF Chinnery, RJ Wilkinson
PloS one 2014
Effect of Zidovudine and its interaction with rocuronium on neuromuscular transmission
MJ Barvaliya, TK Patel, JC Patel, CB Tripathi
Indian journal of pharmaceutical sciences 2013
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U Gandapu, RK Chaitanya, G Kishore, RC Reddy, AK Kondapi, M Antopolsky
PloS one 2011
Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action:
C Bazzoli, V Jullien, CL Tiec, E Rey, F Mentré, AM Taburet
Clinical Pharmacokinetics 2010
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A Fleischman, M Kron, DM Systrom, M Hrovat, SK Grinspoon
The Journal of clinical endocrinology and metabolism 2009
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GK Sakkas, K Mulligan, M DaSilva, JW Doyle, H Khatami, T Schleich, JA Kent-Braun, M Schambelan, G Parise
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Drug Discovery Today 2008
Side Effects of Drugs Annual
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Side Effects of Drugs Annual 2007
Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults
A Fleischman, S Johnsen, DM Systrom, M Hrovat, CT Farrar, W Frontera, K Fitch, BJ Thomas, M Torriani, HC Côté, SK Grinspoon
American journal of physiology. Endocrinology and metabolism 2007
Zidovudine Inhibits Thymidine Phosphorylation in the Isolated Perfused Rat Heart
D Susan-Resiga, AT Bentley, MD Lynx, DD LaClair, EE McKee
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3'-Azido-3'-deoxythymidine (AZT) is a competitive inhibitor of thymidine phosphorylation in isolated rat heart and liver mitochondria
MD Lynx, EE McKee
Biochemical Pharmacology 2006
3'-Azido-3'-deoxythymidine (AZT) inhibits thymidine phosphorylation in isolated rat liver mitochondria: a possible mechanism of AZT hepatotoxicity
MD Lynx, AT Bentley, EE McKee
Biochemical Pharmacology 2006
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AIDS Research and Human Retroviruses 2004
Aerobic Exercise Dysfunction in Human Immunodeficiency Virus: A Potential Link to Physical Disability
WT Cade, L Peralta, RE Keyser
Physical therapy 2004
Mitochondrial dysfunction and nucleoside reverse transcriptase inhibitor therapy: experimental clarifications and persistent clinical questions
W Lewis
Antiviral Research 2003
Decreased peak arteriovenous oxygen difference during treadmill exercise testing in individuals infected with the human immunodeficiency virus
WT Cade, LE Fantry, SR Nabar, RE Keyser
Archives of Physical Medicine and Rehabilitation 2003
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W Lewis
Progress in Cardiovascular Diseases 2003
Drug-induced and toxic myopathies
S Guis, JP Mattéi, F Lioté
Best Practice & Research Clinical Rheumatology 2003
Mitochondrial toxicity of nrti antiviral drugs: an integrated cellular perspective
W Lewis, BJ Day, WC Copeland
Nature Reviews Drug Discovery 2003
Impaired glucose phosphorylation and transport in skeletal muscle causes insulin resistance in HIV-1 infected patients with lipodystrophy
Georg M.N. Behrens, Anne-Rose Boerner, Klaus Weber, Joerg van den Hoff, Johann Ockenga, Georg Brabant, Reinhold E. Schmidt
Journal of Clinical Investigation 2002
Changes in Mitochondrial DNA as a Marker of Nucleoside Toxicity in HIV-Infected Patients
HC Côté, ZL Brumme, KJ Craib, CS Alexander, B Wynhoven, L Ting, H Wong, M Harris, PR Harrigan, MV O'Shaughnessy, JS Montaner
New England Journal of Medicine 2002
Mitochondrial dysfunction and antiretroviral nucleoside analog toxicities: what is the evidence?
T Dagan, C Sable, J Bray, M Gerschenson
Mitochondrion 2002
Mitochondrial DNA Depletion, Oxidative Stress, and Mutation: Mechanisms 0f Dysfunction from Nucleoside Reverse Transcriptase Inhibitors
W Lewis, WC Copeland, BJ Day
Laboratory Investigation 2001
Rheumatic manifestations of current pharmacopeia
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Current Rheumatology Reports 2000
Fetal Mitochondrial Heart and Skeletal Muscle Damage inErythrocebus patasMonkeys Exposedin Uteroto 3'-Azido-3'-Deoxythymidine
M Gerschenson, SW Erhart, CY Paik, MC st. Claire, K Nagashima, B Skopets, SW Harbaugh, JW Harbaugh, W Quan, MC Poirier
AIDS Research and Human Retroviruses 2000
Differential effects of antiretroviral nucleoside analogs on mitochondrial function in HepG2 cells
XR Pan-Zhou, L Cui, XJ Zhou, JP Sommadossi, VM Darley-Usmar
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Functional aerobic impairment in adolescents seropositive for HIV: A quasiexperimental analysis
RE Keyser, L Peralta, WT Cade, S Miller, J Anixt
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The Fatigue Experience for Women With Human Immunodeficiency Virus
KA Lee, CJ Portillo, H Miramontes
Journal of Obstetric, Gynecologic, & Neonatal Nursing 1999
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3′-Azido-3′-deoxythymidine uptake into isolated rat liver mitochondria and impairment of ADP/ATP translocator
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Normalized metabolic stress for 31 P-MR spectroscopy studies of human skeletal muscle: MVC vs. muscle volume
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