Abstract
Chronic kidney disease (CKD) is accompanied by a disturbed redox homeostasis, especially in end-stage patients, which is associated with pathological complications such as anemia, atherosclerosis, and muscle atrophy. However, limited evidence exists about redox disturbances before the end stage of CKD. Moreover, the available redox literature has not yet provided clear associations between circulating and tissue-specific (muscle) oxidative stress levels. The aim of the study was to evaluate commonly used redox status indices in the blood and in two different types of skeletal muscle (psoas, soleus) in the predialysis stages of CKD, using an animal model of renal insufficiency, and to investigate whether blood redox status indices could be reflecting the skeletal muscle redox status. Indices evaluated included reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PC), and thiobarbituric acid reactive substances (TBARS). Results showed that blood GSH was higher in the uremic group compared to the control (17.50 ± 1.73 vs. 12.43 ± 1.01, p = 0.033). In both muscle types, PC levels were higher in the uremic group compared to the control (psoas: 1.086 ± 0.294 vs. 0.596 ± 0.372, soleus: 2.52 ± 0.29 vs. 0.929 ± 0.41, p < 0.05). The soleus had higher levels of TBARS, PC, GSH, CAT, and GR and lower TAC compared to the psoas in both groups. No significant correlations in redox status indices between the blood and skeletal muscles were found. However, in the uremic group, significant correlations between the psoas and soleus muscles in PC, GSSG, and CAT levels emerged, not present in the control. Even in the early stages of CKD, a disturbance in redox homeostasis was observed, which seemed to be muscle type-specific, while blood levels of redox indices did not seem to reflect the intramuscular condition. The above results highlight the need for further research in order to identify the key mechanisms driving the onset and progression of oxidative stress and its detrimental effects on CKD patients.
Highlights
IntroductionRedox homeostasis encompasses the balance between oxidants (or prooxidants) and antioxidants and is maintained by several complex mechanisms
Redox homeostasis encompasses the balance between oxidants and antioxidants and is maintained by several complex mechanisms
Chronic kidney disease is accompanied by enhanced oxidative stress, which in turn is associated with higher risk of developing cardiovascular disease (CVD), leading to high rates of morbidity and mortality [3, 4]
Summary
Redox homeostasis encompasses the balance between oxidants (or prooxidants) and antioxidants and is maintained by several complex mechanisms. The harmful effects of oxidative stress have been associated with the progression of CKD, its role during the different stages of the disease has not yet, been fully clarified. Patients may progress to renal insufficiency as a secondary outcome of variable primary conditions, from hypertension, diabetes, nephrotic syndrome, etc. Oxidative stress in predialysis CKD can be attributed to the cytotoxic effects of the progressive loss of renal function as well as insufficient antioxidant defense [11]. Several mechanisms link CKD and oxidative stress, such as uremic toxin-induced endothelial nitric oxide synthase (eNOS) uncoupling [12] and increased nicotinamide adenine dinucleotide phosphate-oxidases (NADPH oxidases (NOX)) activity [13]. An emerging antioxidant deficit has been attributed mainly to dietary restrictions, diuretics use, protein energy wasting, and/or decreased intestinal absorption [14, 15]
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