NDT Advance Access originally published online on January 8, 2007
Nephrology Dialysis Transplantation 2007 22(4):1177-1183; doi:10.1093/ndt/gfl721
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Markers of oxidative stress in the skeletal muscle of patients on haemodialysis
1Division of Metabolic and Cellular Medicine, School of Clinical Sciences, University of Liverpool and 2Renal Unit, Royal Liverpool University and Broadgreen Hospitals NHS Trust, Liverpool, UK
Correspondence and offprint requests to: Prof. M. J. Jackson, Division of Metabolic and Cellular Medicine, University of Liverpool, Liverpool L69 3GA, UK. Email: mjj{at}liv.ac.uk
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Abstract |
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Background. Increased oxidative stress may play a role in morbidity and mortality of patients with renal failure. Most studies have examined serum markers of oxidation, but it is unclear whether oxidative stress is involved in skeletal muscle atrophy.
Methods. This study examined markers of oxidative stress in the skeletal muscle of 10 haemodialysed patients and 10 control subjects. Biopsies from the quadriceps femoris were analysed for reduced and oxidized glutathione, protein thiols, malonaldehyde and heat shock proteins (HSP27, HSP60 and HSP70), superoxide dismutase and catalase activities. A novel microdialysis procedure was used to examine hydroxyl radical activity in the interstitial fluid of the tibialis anterior.
Results. Patients had muscle atrophy with a reduced diameter of both type I and II fibres (by 15 and 20%, respectively). Muscle microdialysates contained 2,3- and 2,5-dihydroxybenzoates formed from salicylate indicating hydroxyl radical activity, with no differences between patients and control subjects. Muscle protein thiol and oxidized glutathione contents were unchanged in patients, but malonaldehyde content was reduced. In contrast, total muscle glutathione and heat shock protein contents were increased. Muscle superoxide dismutase activity was unchanged, but catalase activity was reduced in patients.
Conclusions. The muscle of patients undergoing haemodialysis undergoes some adaptive responses in total glutathione content, heat shock protein content and catalase activity that are potentially related to chronic oxidative stress. However, there is no evidence of gross oxidation, nor any clear relationship between oxidative stress and muscle fibre atrophy, arguing against a direct role of oxidants in the degenerative processes.
Keywords: free radicals; glutathione; heat shock proteins; microdialysis; reactive oxygen species
Received for publication: 20.12.05
Accepted in revised form: 7.11.06