scholarly journals Advanced oxidation protein products contribute to chronic kidney disease‐induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway

Author(s):  
Hiromasa Kato ◽  
Hiroshi Watanabe ◽  
Tadashi Imafuku ◽  
Nanaka Arimura ◽  
Issei Fujita ◽  
...  
2018 ◽  
Vol 21 (6) ◽  
pp. 465-474 ◽  
Author(s):  
Emanuela Valle ◽  
Liviana Prola ◽  
Diana Vergnano ◽  
Roberta Borghi ◽  
Fiammetta Monacelli ◽  
...  

Objectives Cats are commonly affected by chronic kidney disease (CKD). Many reactive carbonyl intermediates and end products originating from the oxidative stress pathways are recognised as uraemic toxins and may play a role in CKD progression. The aim of the present study is to confirm whether carbonyl end-product formation is higher in cats affected by CKD and to assess whether an angiotensin-converting enzyme inhibitor (ACEi) might affect these hallmarks. Methods Twenty-two cats were divided into three groups: a control group (CG), cats with CKD and cats with CKD treated with an ACEi. Serum levels of pentosidine, carboxymethyllysine, advanced oxidation protein products, malondialdehyde, methylglyoxal and hexanoyl-lysine were measured. In addition, biochemical parameters and systolic blood pressure were evaluated. After checking for normality, comparisons between groups were performed followed by multiple comparison tests. P values ⩽0.05 were considered significant. Correlations between concentrations of the considered biomarkers and of the other metabolic parameters were investigated. Results Advanced oxidation protein products, malondialdehyde and hexanoyl-lysine concentrations were significantly higher in CKD and ACEi-treated groups compared with the CG ( P <0.05). Carboxymethyllysine increased in the ACEi-treated group when compared with the CG, whereas intermediate values of these biomarkers were found in the CKD group ( P <0.05). The ACEi-treated group showed the highest values of carboxymethyllysine, advanced oxidation protein products and hexanoyl-lysine. By contrast, the CKD group had the highest concentration of malondialdehyde. No statistically significant difference was found in the levels of pentosidine or methylglyoxal. End products correlated with creatinine and urea and with each other. Conclusions and relevance Significantly high concentrations of both intermediate and end products of carbonyl/oxidative stress were detected in CKD cats. This is the first study to have concurrently taken into account several uraemic toxins and biochemical parameters in cats affected by CKD.


2015 ◽  
Vol 28 (1) ◽  
pp. 17-20 ◽  
Author(s):  
Larissa Yevgenyevna Muravlyova ◽  
Vilen Borisovich Molotov-Luchankiy ◽  
Ryszhan Yemelyevna Bakirova ◽  
Anar Akylbekovna Turmukhambetova ◽  
Dmitriy Anatolyevich Klyuyev ◽  
...  

Abstract Recent findings have demonstrated the impaired functions of neutrophils of patients with chronic renal failure. The purpose of our research was to study oxidative modified proteins, as well as the histone spectrum in neutrophils drawn from patients with chronic kidney disease, and to estimate the ability of neutrophils to form spontaneous neutrophil extracellular traps. In this work, we have assumed that metabolic alteration in neutrophils may develop at early stages of chronic kidney disease. Materials and methods: Neutrophils obtained from patients with various stages of chronic kidney disease and degrees of chronic renal failure were used. As control, blood samples obtained from 32 healthy individuals was employed. In the examined neutrophils, advanced oxidation protein products, protein reactive carbonyl derivatives, as well as nucleosomal histones were detected. The ability of neutrophils to form spontaneous neutrophil extracellular traps was estimated. Our results have demonstrated an increase of nucleosomal histones in neutrophils of all patients with chronic kidney disease. Moreover, our work fixes the rate of growth of intracellular advanced oxidation protein products and the decreasing of protein reactive carbonyl derivatives in neutrophils from patients with chronic kidney disease. Furthermore, we demonstrate the presence of the neutrophils with altered oxidative status and the decomposition of the histone spectrum in the circulation of patients with chronic kidney disease.


2017 ◽  
Vol 312 (1) ◽  
pp. C47-C55 ◽  
Author(s):  
Mirandy S. Li ◽  
Sherry E. Adesina ◽  
Carla L. Ellis ◽  
Jennifer L. Gooch ◽  
Robert S. Hoover ◽  
...  

Zn2+ deficiency (ZnD) is comorbid with chronic kidney disease and worsens kidney complications. Oxidative stress is implicated in the detrimental effects of ZnD. However, the sources of oxidative stress continue to be identified. Since NADPH oxidases (Nox) are the primary enzymes that contribute to renal reactive oxygen species generation, this study's objective was to determine the role of these enzymes in ZnD-induced oxidative stress. We hypothesized that ZnD promotes NADPH oxidase upregulation, resulting in oxidative stress and kidney damage. To test this hypothesis, wild-type mice were pair-fed a ZnD or Zn2+-adequate diet. To further investigate the effects of Zn2+ bioavailability on NADPH oxidase regulation, mouse tubular epithelial cells were exposed to the Zn2+ chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) or vehicle followed by Zn2+ supplementation. We found that ZnD diet-fed mice develop microalbuminuria, electrolyte imbalance, and whole kidney hypertrophy. These markers of kidney damage are accompanied by elevated Nox2 expression and H2O2 levels. In mouse tubular epithelial cells, TPEN-induced ZnD stimulates H2O2 generation. In this in vitro model of ZnD, enhanced H2O2 generation is prevented by NADPH oxidase inhibition with diphenyleneiodonium. Specifically, TPEN promotes Nox2 expression and activation, which are reversed when intracellular Zn2+ levels are restored following Zn2+ supplementation. Finally, Nox2 knockdown by siRNA prevents TPEN-induced H2O2 generation and cellular hypertrophy in vitro. Together, these findings reveal that Nox2 is a Zn2+-regulated enzyme that mediates ZnD-induced oxidative stress and kidney hypertrophy. Understanding the specific mechanisms by which ZnD contributes to kidney damage may have an important impact on the treatment of chronic kidney disease.


Redox Report ◽  
2014 ◽  
Vol 20 (3) ◽  
pp. 126-132 ◽  
Author(s):  
Kassia S Beetham ◽  
Erin J Howden ◽  
David M Small ◽  
David R Briskey ◽  
Megan Rossi ◽  
...  

Author(s):  
Patricia Tomás-Simó ◽  
Luis D’Marco ◽  
María Romero-Parra ◽  
Mari Carmen Tormos-Muñoz ◽  
Guillermo Sáez ◽  
...  

Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. Methods: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2’-deoxyguanosine (8-oxo-dG). Results: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. Conclusions: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.


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