scholarly journals Cardiac Inflammation, Oxidative Stress, Nrf2 Expression, and Coagulation Events in Mice with Experimental Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Abderrahim Nemmar ◽  
Suhail Al-Salam ◽  
Sumaya Beegam ◽  
Nur Elena Zaaba ◽  
Javed Yasin ◽  
...  

Chronic kidney disease (CKD) is known to be associated with cardiovascular dysfunction. Dietary adenine intake in mice is also known to induce CKD. However, in this experimental model, the mechanisms underlying the cardiotoxicity and coagulation disturbances are not fully understood. Here, we evaluated cardiac inflammation, oxidative stress, DNA damage, and coagulation events in mice with adenine (0.2% w / w in feed for 4 weeks)-induced CKD. Control mice were fed with normal chow for the same duration. Adenine increased water intake, urine output, relative kidney weight, the plasma concentrations of urea and creatinine, and the urinary concentrations of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It also decreased the body weight and creatinine clearance, and caused kidney DNA damage. Renal histological analysis showed tubular dilation and damage and neutrophilic influx. Adenine induced a significant increase in systolic blood pressure and the concentrations of troponin I, tumor necrosis factor-α, and interleukin-1β in heart homogenates. It also augmented the levels of markers of lipid peroxidation measured by malondialdehyde production and 8-isoprostane, as well as the antioxidants superoxide dismutase and catalase. Immunohistochemical analysis of the hearts showed that adenine increased the expression of nuclear factor erythroid-derived 2-like 2 by cardiomyocytes. It also caused cardiac DNA damage. Moreover, compared with the control group, adenine induced a significant increase in the number of circulating platelet and shortened the thrombotic occlusion time in pial arterioles and venules in vivo, and induced a significant reduction in the prothrombin time and activated partial thromboplastin time. In conclusion, the administration of adenine in mice induced CKD-associated cardiac inflammation, oxidative stress, Nrf2 expression, and DNA damage. It also induced prothrombotic events in vivo. Therefore, this model can be satisfactorily used to study the cardiac pathophysiological events in subjects with CKD and the effect of drug treatment thereon.

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.


2018 ◽  
Vol 7 (8) ◽  
pp. 209 ◽  
Author(s):  
Mateusz Maciejczyk ◽  
Julita Szulimowska ◽  
Anna Skutnik ◽  
Katarzyna Taranta-Janusz ◽  
Anna Wasilewska ◽  
...  

There are still missing non-invasive biomarkers of chronic kidney disease (CKD) in children. Therefore, the aim of the study was to evaluate oxidative stress indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD children (n = 25) and healthy controls (n = 25). Salivary antioxidants (catalase (CAT), peroxidase (Px), superoxide dismutase (SOD), uric acid (UA), reduced glutathione (GSH), albumin), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were evaluated. We have demonstrated the significantly higher activity of SWS GPx and SOD, as well as elevated concentrations of UA and albumin in NWS and SWS of CKD children vs. the control group. TAC, TOS and OSI were significantly higher only in SWS, while oxidative damage products (AGE, AOPP and MDA) were significantly higher in both NWS and SWS of CKD children. ROC analysis showed a considerably high diagnostic value of AOPP in both NWS and SWS of CKD children compared to controls (AUC = 0.92; 0.98). CKD is responsible for disturbances in salivary antioxidant systems and oxidative damage to proteins and lipids. Salivary AOPP can be a potential biomarker of CKD in children.


Author(s):  
M. Kolesnyk ◽  
L. Korol ◽  
L. Migal ◽  
O. Burdeyna ◽  
V. Novakivskyy

The object was to study the effect of oxidative factors and methods of renal replacement therapy (RRT) on indices of oxidative stress (OS) and resistance cells in blood in patients with chronic kidney disease stage V(CKD VD) and anemic syndrome. Material and methods. The study involved 47 patients with CKD VD: 14patients were treated by hemodiafiltration (HDF), 14 patients by hemodialysis (HD) and 19 patients by peritoneal dialysis (PD). The severity ofanemia was assessed according to the KDIGO (2012) criteria. The control group consisted of30 healthy people of the same age and sex. Along with the standard diagnostic methods, we defined the content of malonic dialdehyde in serum (MDAs) and in erythrocytes (MDAe), the content of ceruloplasmin (CPs), transferrin (TRs) and SH - groups in the blood serum, the index of the OS (IOS), catalase activity in serum (CTs), glucose - 6 - phosphate dehydrogenase (G - 6 - PDHe) and total peroxidase activity (TPA) in erythrocyte, osmotic (OR) and peroxide resistance (PR) of red blood cells and erythrocyte membrane permeability (EMP). Statistical analysis was performed using the programs Microsoft Excel 5,0 and MedStat. Results. It has been stated that in the CKD VD patients agains the rates in control group the MDAs content increased by 3.3 times and MDAe - 1.2 times, TRs content reduced by 34%, SH - groups - by 31%, TPAe - by 41% and G - 6 - FDGe - by 58%, marcers of OR by 30%, PR - by 60%; 4.6 times increased CTs activity and OSI; 2 times grew peroxide hemolysis (PH) and 1.3 times - EMP. The analysis (depending on the RRT modality) showed that the patients treated by HDF had typical MDAs increase by 3.9 times on a background of CPs by 24%o, TRs - 33%, SH - groups - 25%, TPAe - 51%, G6 - PDHe - 42%; the increase in serum OSI - 5.4 times and 2.6 times in erythrocytes, PR - by 3.6 times and CTs activity by 3,5 times; HD group were characterized by the highest value of MDAe, OSI, PH and CTs, along with more expressed decrease of indices TRs, SH - groups, TPA and G - 6 - FDHe activity compared with rates in patients with HDF. The patients treated with PD had the lowest content of MDAs and the highest values on the background ofTPAe, the significant increase of CPs by 1.7 times and lowest TRs and G - 6 - PDHe. The patients with PD showed twice lower OS activity by OSI. Conclusion.Thus, in patients with CKD VD, who had HD, HDF or PD an anemic syndrome was associated with high OS activity and the increased degree of hemolysis. These changes are stipulated by RRT methods: for patients receiving HDF were typical the lowest rates of hemolysis and the highest degree of protection for erythrocytes, and for patients treated with HD - the highest OS.


2010 ◽  
Vol 1 (3) ◽  
pp. 146
Author(s):  
MOCHAMMAD THAHA ◽  
Widodo Widodo ◽  
Moh. Yogiantoro ◽  
WENNY PUTRI NILAMSARI ◽  
MOCHAMAD YUSUF ◽  
...  

Background: Uremic patients are in a pro-oxidant state and show an increased level of asymmetric dimethylarginine (ADMA), which is due to increased PRMT1 activity and reduced dimethylarginine dimethylaminohydrolase (DDAH) as degradation enzymes. Reactive oxidant species may play an important role in increasing the action of PRMT1 and in inhibiting the action of DDAH. Albuminuria and ADMA are closely correlated with progression of cardiovascular disease in chronic kidney disease (CKD) patients as well as indicators for decreasing renal function. Although ACEIs and/or ARBs reduced albuminuria in CKD patients, the results are still conflicting. Several factors in these patients may play important roles in the mechanism of albuminuria such as oxidative stress. The antioxidant N-acetylcysteine may prove to have beneficial therapeutic effect, because it can reduce oxidative stress as shown by evidence in humans, and subsequently increase ADMA. The objective of the present study is to explore the contribution of the antioxidant N-acetylcysteine (NAC) to the decrease of ADMA and albuminuria in non-diabetic CKD patients. Material and Methods: Patients with non-DM CKD stage 1–4 with albuminuria were randomized to receive ACEI and/or ARB alone (control group) or with antioxidant NAC 600 mg orally twice a day (treatment group). Observations were performed for 3 months to measure ADMA and albuminuria before and after-treatment. 80 patients in total 40 in the control group and 40 in the treatment group were used. Results: After oral treatment with NAC, the plasma level of ADMA in the treatment group increased from 0.604 µmol/l to 0.689 µmol/l, whereas ADMA level in the control group exhibited a higher increase from 0.561 µmol/l to 0.743 µmol/l. The increases in these groups were significantly different (p < 0.02). Moreover, the level of albuminuria was reduced from 148.12 µg/mg • cr to 132.7 µg/mg • cr in the treatment group, and from 75.25 µg/mg • cr to 71.85 µg/mg • cr in the control group. The difference was significant (p < 0.001). Conclusion: The anti-oxidant N-acetylcysteine can be used as adjuvant therapy to inhibit the progression of CKD in patients by decreasing the ADMA level and albuminuria.


2017 ◽  
Vol 20 (10) ◽  
pp. 940-947 ◽  
Author(s):  
Ines Matos ◽  
Pedro Azevedo ◽  
L Miguel Carreira

Objectives Chronic kidney disease (CKD) is the most common renal pathology diagnosed in geriatric cats, and its prevalence increases with age. The arterial resistive index (RI) is important when evaluating vascular resistance and compliance, and can be applied in the kidney (renal RI [RRI]), allowing the evaluation of its vascular haemodynamics. The present study aimed to: (1) investigate in cats with CKD the relationships between the RRI and the following parameters: age, sex, body weight, plasmatic creatinine, blood urea nitrogen, potassium, urine specific gravity, urine protein:creatinine ratio and systolic arterial pressure; and (2) evaluate the potential use of the RRI as a preliminary diagnostic tool in cats with CKD. Methods The present study involved 24 cats of both sexes. Six were healthy cats (control group [CG]) and 18 had CKD, but did not have any concomitant diseases and were not being treated with any medications (study group [SG]). For RRI measurement we used colour Doppler ultrasound (CDUS). Results RRI differed significantly between the CG and SG ( P <0.01) and was higher in the SG. A statistically significant correlation was only achieved between the RRI and the body weight of the patients and it was negative. A strong and positive correlation was noted between the mean RRI of both kidneys (r = 0.66). Receiver–operating curve analysis allowed us to establish an admissible cut-off for the RRI value of 0.639 for a preliminary diagnosis of CKD for both kidneys. Conclusions and relevance No differences were found for the RRI between the left and right kidneys, suggesting that evaluation of only one kidney is sufficient to provide an estimate of the RRI value for both organs. RRI measurement, which can be achieved with CDUS, is an easy-to-use diagnostic tool that, with a cut-off value of 0.639 for both kidneys, is useful in establishing a preliminary diagnosis of CKD.


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.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S154-S154
Author(s):  
A S Boraik ◽  
M Abdelmonem ◽  
M Shedid ◽  
H M Abd Elaal ◽  
A Elhusseny ◽  
...  

Abstract Introduction/Objective Chronic kidney disease (CKD) is affecting about 14% of the general population. CKD is associated with a decrease in calcium level in the body. In the early stages of (CKD), dialysis may not be needed. The late stages of CKD will require dialysis or a kidney transplant to save a life. Secondary hyperparathyroidism is a crucial disorder in CKD patients. It explains why the illness causes a significant change in bone and mineral metabolism. This study aims to study renal hyperparathyroidism (rHPT) in dialysis patients with late-stage of chronic kidney disease (CKD). Methods/Case Report A total of 55 subjects were enrolled in this study for late-stage dialysis patients from Egypt. Serum creatinine and PTH levels were measured. Among the 55 subjects; 41 subjects (74.5%) were males, 14 subjects (25.5%) were females with a mean age of 52.7 and 34.3 years for males and females, respectively. Subjects were divided into two groups; Study group I consists of 33 dialysis patients; three patients were females (9%) while 30 patients were males (91%), and control group II consists of 22 healthy individuals, 11 subjects were females (50%), and 11 subjects were males (50%). Results (if a Case Study enter NA) In our study, in comparison between two groups as regards blood investigations. The means of creatinine and PTH in the study group I were 8.93 mg/dl and 316.8, while in the control group II were 0.9, and 38.4 respectively. Comparing the two groups shows that mean of Creatinine and PTH in the study group was statistically significantly higher than the control group (p-value less than 0.001). Conclusion In patients with CKD, accurate measurement of (PTH) is critical for treatment decision-making to reduce the risk of bone and cardiovascular diseases. We recommend that patients with diabetes and high blood pressure be aware that they must take their medications consistently to avoid kidney problems.


2019 ◽  
Vol 9 (6) ◽  
pp. 412
Author(s):  
Amrendra K. Ajay ◽  
Shritu Vig ◽  
Venkata S. Sabbisetti

Chronic kidney disease (CKD) is a general term for a diverse variety of cause affecting kidney structure and function. The term “chronic” is because the damage to the kidneys happens slowly over a long period of time. Damaged kidneys cannot filter extra water and wastes out of blood as compared to the healthy kidneys. The disease prognosis and control are categorized based on disease severity, which is evaluated by glomerular filtration rate (GFR) and albuminuria, and clinical diagnosis. Progression of CKD thus causes wastes to build up in the body and is associated with a number of severe complications, including increased incidence of cardiovascular disease, hyperlipidemia, anemia, and metabolic bone disease.Forty percent of CKD is a result of complications associated with diabetes. Patients with diabetes are suggested to intake reduced amount of carbohydrates and increased amount of proteins. Patients with CKD are suggested to intake a low protein diet. Thus, there is a fine need for CKD patients to understand the food constituents and functional components. Given the intricacies of the renal diet and the difficulties faced by patients due to conflicting recommendations and complexities faced in understanding processed food labels, there is a lot of emphasis in the present world to change the focus in CKD away from what not to eat to the concept of good nutrition as positive medicine or therapy for kidney patients.Specifically, there has been a surge in consumer interest on the beneficial role of specific foods with physiologically-active food components, so-called functional foods benefitting CKD. In the past century, increased attention to lifestyle and healthy diets has led to an increase in demand for functional foods.Thus, this review will discuss the key components that have been in investigated in vivo using rodent models, some clinical trials and studies for being identified as a ‘nutraceuticals’ for patients with CKD.KEYWORDS: Chronic kidney disease, Functional food, Conjugated Linoleic acid, LDL, HDL, Protein diet, Omega fatty acids, L-Carnitine.


2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Lin Luo ◽  
Ying Zhang

Objective In the past few decades, the study of skeletal muscle oxidative stress has been concerned about the increase of free radicals induced by muscle contraction. In recent years, the activation of antioxidant stress signaling pathway has gradually become one of the hot topics in the field of sports medicine. Although current research has confirmed that long-term aerobic training can bring health benefits to the body, the molecular mechanism of its role is still not very clear.Traditionally, AMPK has been regarded as the energy receptor of cells. During exercise, the energy consumption of skeletal muscle doubled, ATP decreased, AMP increased, and the ratio of AMP/ATP increased, thus inducing the activation of AMPK and regulating cell energy metabolism. Recent studies have found that AMPK not only plays an important role in the regulation of energy metabolism, but also plays a role in the body's antioxidant stress response. However, the relationship between AMPK and oxidative stress has been studied only in a small number of cells in non skeletal muscle cells. The results of this few studies show that oxidative stress in AMPK can not depend on the increase of intracellular AMP/ATP ratio, and the independent activation of AMPK, thus reducing the level of intracellular ROS, but the molecular mechanism of its action is not clear. Nrf2 is an important nuclear transcription factor in the body and plays an important role in the body's antioxidant stress response. Whether AMPK can participate in the regulation of Nrf2 mediated antioxidant activity in skeletal muscle has not been reported.In this study, the mouse skeletal muscle C2C12 cells were used in vitro cell experiments. The AMPK pharmacologic activator AICAR and the pharmacological inhibitor Compound C were used to treat the cells respectively. The role of AMPK in the regulation of Nrf2 expression in C2C12 cells and its mechanism were observed.  Methods Cell experiments were performed on C2C12 cells of skeletal muscle of mice, and AMPK activator AICAR and AMPK inhibitor Compound C were used to intervene. The fluorescence intensity of C2C12 cells in each group was qualitatively detected by fluorescence inverted microscope, and the ROS level of C2C12 cells in each group was detected by fluorescence colorimetry. Results the ROS level of each group was significantly higher than that of the control group. RT-PCR assay was used to detect the antioxidant enzyme mRNA level of C2C12 cells in each group. Western Blot assay was used to detect the expression of AMPK alpha, pAMPK alpha, Nrf2, pNrf2 and antioxidant enzyme protein in C2C12 cells of each group.  Results (1) compared with the control group, the pAMPK alpha /AMPK alpha ratio of C2C12 cells in the agonist group increased significantly, the expression of pNrf2 protein in the cells increased significantly, and the expression of NQO1mRNA, HO-1mRNA and GSR mRNA increased significantly, and the cells SOD1, GCLM, NQO1, HO-1, pNrf2, and protein were significantly increased. Low. (2) compared with the control group, the levels of NQO1mRNA, HO-1mRNA, CATmRNA, SOD1mRNA, Gpx-1mRNA and GCLc mRNA in the C2C12 cells of the inhibitor group decreased significantly, and the expression of NQO1 and GCLM proteins in the cells decreased significantly, and the ROS level of the cells increased significantly.  Conclusions  (1) the activation of AMPK by AICAR activates the increase of Nrf2 activation in skeletal muscle C2C12 cells, and then increases the expression of mRNA and protein (SOD1, GCLM, NQO1, NQO1, GSR) in the downstream of Nrf2 (NQO1, HO-1, GSR), and significantly reduces the intracellular level.(2) the inhibition of AMPK by Compound C significantly decreased the mRNA expression of C2C12 cells (NQO1, HO-1, CAT, SOD1, Gpx-1, GCLc) in skeletal muscle, and significantly decreased the expression of protein (NQO1 and GCLc)


Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 176
Author(s):  
Anna Gvozdjáková ◽  
Zuzana Sumbalová ◽  
Jarmila Kucharská ◽  
Mária Komlósi ◽  
Zuzana Rausová ◽  
...  

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and a decrease of glomerular filtration rate. Reduced mitochondrial function, coenzyme Q10 (CoQ10), and increased oxidative stress in patients with CKD contribute to the disease progression. We tested whether CoQ10 levels, oxidative stress and platelet mitochondrial bioenergetic function differ between groups of CKD patients. Methods: Twenty-seven CKD patients were enrolled in this trial, 17 patients had arterial hypertension (AH) and 10 patients had arterial hypertension and diabetes mellitus (AH and DM). The control group consisted of 12 volunteers. A high-resolution respirometry (HRR) method was used for the analysis of mitochondrial bioenergetics in platelets, and an HPLC method with UV detection was used for CoQ10 determination in platelets, blood, and plasma. Oxidative stress was determined as thiobarbituric acid reactive substances (TBARS). Results: Platelets mitochondrial respiration showed slight, not significant differences between the groups of CKD patients and control subjects. The oxygen consumption by intact platelets positively correlated with the concentration of CoQ10 in the platelets of CKD patients. Conclusion: A decreased concentration of CoQ10 and oxidative stress could contribute to the progression of renal dysfunction in CKD patients. The parameters of platelet respiration assessed by high-resolution respirometry can be used only as a weak biological marker for mitochondrial diagnosis and therapy monitoring in CKD patients.


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