Protective role of peroxiredoxin-4 in heart failure

2020 ◽  
Vol 134 (1) ◽  
pp. 71-72
Author(s):  
Naseer Ahmed ◽  
Masooma Naseem ◽  
Javeria Farooq

Abstract Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471–1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that ‘antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.’ We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

2018 ◽  
Vol 132 (13) ◽  
pp. 1471-1485 ◽  
Author(s):  
Jaime Ibarrola ◽  
Vanessa Arrieta ◽  
Rafael Sádaba ◽  
Ernesto Martinez-Martinez ◽  
Amaia Garcia-Peña ◽  
...  

Galectin-3 (Gal-3) is increased in heart failure (HF) and promotes cardiac fibrosis and inflammation. We investigated whether Gal-3 modulates oxidative stress in human cardiac fibroblasts, in experimental animal models and in human aortic stenosis (AS). Using proteomics and immunodetection approaches, we have identified that Gal-3 down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. In parallel, Gal-3 increased peroxide, nitrotyrosine, malondialdehyde, and N-carboxymethyl-lysine levels and decreased total antioxidant capacity. Gal-3 decreased prohibitin-2 expression without modifying other mitochondrial proteins. Prx-4 silencing increased oxidative stress markers. In Gal-3-silenced cells and in heart from Gal-3 knockout mice, Prx-4 was increased and oxidative stress markers were decreased. Pharmacological inhibition of Gal-3 with modified citrus pectin restored cardiac Prx-4 as well as prohibitin-2 levels and improved oxidative status in spontaneously hypertensive rats. In serum from 87 patients with AS, Gal-3 negatively correlated with total antioxidant capacity and positively correlated with peroxide. In myocardial biopsies from 26 AS patients, Gal-3 up-regulation paralleled a decrease in Prx-4 and in prohibitin-2. Cardiac Gal-3 inversely correlated with Prx-4 levels in myocardial biopsies. These data suggest that Gal-3 decreased Prx-4 antioxidant system in cardiac fibroblasts, increasing oxidative stress. In pathological models presenting enhanced cardiac Gal-3, the decrease in Prx-4 expression paralleled increased oxidative stress. Gal-3 blockade restored Prx-4 expression and improved oxidative stress status. In AS, circulating levels of Gal-3 could reflect oxidative stress. The alteration of the balance between antioxidant systems and reactive oxygen species production could be a new pathogenic mechanism by which Gal-3 induces cardiac damage in HF.


2020 ◽  
Vol 134 (1) ◽  
pp. 73-74
Author(s):  
Natalia López-Andrés

Abstract We thank Ahmed et al. for their letter regarding our study ‘Galectin-3 down-regulates antioxidant peroxiredoxin-4 in human cardiac fibroblasts’ [1]. As emphasized by Ahmed et al., Prx-4 levels decrease [2] whereas MFN-2, OPA-1 and PGC-1α levels increase [3] in dilated cardiomyopathy (DCM). Moreover, Gal-3 expression is also increased in DCM [4]. In our study, we showed in vitro that Gal-3 decreased Prx-4 without modifying MFN-2 or PGC-1α levels in human cardiac fibroblasts. Although cardiac Prx-4 decrease could be a direct consequence of Gal-3 effects on cardiac fibroblasts, we cannot exclude the possibility that other factors increase MFN-2, OPA-1 and PGC-1α levels in both cardiac fibroblasts or cardiomyocytes in the context of DCM. Further studies are needed to clarify the association between Prx-4 decrease and the increase in other mitochondrial proteins in DCM.


Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Shima Fathi ◽  
Mohammad Taghi Goodarzi ◽  
Shiva Borzouei ◽  
Jalal Poorolajal ◽  
...  

Background: One of the most common complications of pregnant women is gestational diabetes mellitus (GDM). Oxidative stress can play an important role in GDM. Objective: The aim of this study was to evaluate salivary antioxidants and oxidative stress markers in GDM. Method: Twenty pregnant women with GDM and 20 healthy pregnant women with normal blood glucose test participated in this study. Five mL of unstimulated saliva samples were collected. Spectrophotometric assay was carried out for sialochemical analysis. Stata software was used for data analysis. Results: The GDM group exhibited no significant difference in salivary total antioxidant capacity and malondialdehyde compared to the healthy control group. All of antioxidants markers, the uric acid, total antioxidant, peroxidase and catalase, decreased in GDM group that the difference of peroxidase and catalase was statistically significant. All of oxidative stress markers, the salivary malondyaldehid, total oxidative stress and total thiol, increased in GDM group. GDM group exhibited significantly higher salivary total oxidative stress levels. Conclusion: Catalase level was significantly lower and total oxidative stress was significantly higher. These two markers might have significant importance and might exhibit early changes compared to other factors in GDM. . Some of salivary antioxidants might have diagnostic, prognostic or therapeutic implications in GDM. Other studies with large sample size on salivary and blood samples need to be done to confirm this properties and salivary samples using instead of blood samples in GDM biomarkers changes.


2010 ◽  
Vol 25 (4) ◽  
pp. 357-361 ◽  
Author(s):  
Sergio Botelho Guimarães ◽  
Osamu Sandes Kimura ◽  
Paulo Roberto Leitão de Vasconcelos

PURPOSE: To evaluate the protective role of dimethylsulfoxide (DMSO) in a rat model of testis ischemia/reperfusion (I/R). METHODS: Twenty-four male Wistar rats were randomized in two equal groups. Control rats (G-1) received saline 2.0 ml intraperitoneally (ip) 21, 9 and 1 h before torsion. Experimental rats (G-2) received ip injections of 3% aqueous solution of DMSO, 0.1ml/10g body weight. Saline was added to complete 2.0ml when necessary. I/R injury was induced in anesthetized rats by torsion of the right testis lasting 3 hours. Testis and blood samples were collected at the end of ischemia (T-0) and 3 hours later (T-3) for assessment of testis malonaldehyde (MDA), reduced glutathione (GSH), and plasma total antioxidant power (TAP). RESULTS: MDA levels decreased significantly in G-2 rats compared with G-1 animals in all time-points. GSH levels increased significantly in T-0 and T-3 time-points in DMSO pretreated rats compared with G-1 rats. GSH levels increased significantly during reperfusion in G-2 rats. TAP was similar in both groups denoting absence of systemic effects in this study. CONCLUSION: Pretreatment with DMSO reduces testis lipid peroxidation and oxidative stress caused by torsion/detorsion of the testis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena C. Gross ◽  
Niveditha Putananickal ◽  
Anna-Lena Orsini ◽  
Deborah R. Vogt ◽  
Peter S. Sandor ◽  
...  

AbstractIncreasing evidence points towards the role of mitochondrial functioning, energy metabolism, and oxidative stress in migraine. However not all previous research has been conclusive and some mitochondrial function/oxidative stress markers have not yet been examined. To this end, alpha-lipoic acid (ALA), total thiols, total plasma antioxidant capacity (TAC), lipid peroxide (PerOx), oxidised LDL (oxLDL), HbA1c and lactate were determined in the serum of 32 higher frequency episodic migraineurs (5–14 migraine days/ months, 19 with aura, 28 females) in this cross-sectional study. The majority of patients had abnormally low ALA and lactate levels (87.5% and 78.1%, respectively). 46.9% of the patients had abnormally high PerOx values, while for thiols and TAC over one third of patients had abnormally low values (31.2% and 37.5%, respectively). 21.9% of patients had abnormally low HbA1c and none had an HbA1c level above 5.6%. oxLDL was normal in all but one patient. This study provides further evidence for a role of oxidative stress and altered metabolism in migraine pathophysiology, which might represent a suitable therapeutic target. ALA, being too low in almost 90% of patients, might represent a potential biomarker for migraine. Further research is needed to replicate these results, in particular a comparison with a control group.This study is part of the trial registration: ClinicalTrials.gov: NCT03132233, registered on 27.04.2017, https://clinicaltrials.gov/ct2/show/NCT03132233.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Alenka Nemec Svete ◽  
Barbara Verk ◽  
Nina Čebulj-Kadunc ◽  
Janez Salobir ◽  
Vida Rezar ◽  
...  

Abstract Background Inflammation and oxidative stress can contribute to the development and progression of heart failure. This study aimed to investigate the association between inflammatory and oxidative stress markers in dogs with congestive heart failure (CHF). Associations between the disease severity marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) and markers of inflammation and oxidative stress were also determined. Results Thirty-seven dogs with cardiovascular diseases (dilated cardiomyopathy, DCM (16 dogs), myxomatous mitral valve disease, MMVD (21 dogs)) and ten healthy dogs were included in this prospective study. The patients were further divided into groups with (26) and without CHF (11). We found a significantly higher serum concentration of C-reactive protein (P = 0.012), white blood cell (P = 0.001), neutrophil (P = 0.001) and monocyte counts (P = 0.001) in patients with CHF compared to control dogs. The concentration of tumor necrosis factor-alpha (TNF-α) was significantly higher in patients with CHF compared to patients without CHF (P = 0.030). No significant difference was found in most of the measured parameters between MMVD and DCM patients, except for glutathione peroxidase (GPX) and NT-proBNP. In patients with CHF, TNF-α correlated positively with malondialdehyde (P = 0.014, r = 0.474) and negatively with GPX (P = 0.026, r = − 0.453), and interleukin-6 correlated negatively with GPX (P = 0.046, r = − 0.412). NT-proBNP correlated positively with malondialdehyde (P = 0.011, r = 0.493). In patients without CHF none of the inflammatory and oxidative stress markers correlated significantly. Furthermore, in the group of all cardiac patients, GPX activity significantly negatively correlated with NT-proBNP (P = 0.050, r = − 0.339) and several markers of inflammation, including TNF-α (P = 0.010, r = − 0.436), interleukin-6 (P = 0.026, r = − 0.382), white blood cell (P = 0.032, r = − 0.369), neutrophil (P = 0.027, r = − 0.379) and monocyte counts (P = 0.024, r = − 0.386). Conclusion Inflammatory and oxidative stress markers are linked in canine CHF patients, but not in patients without CHF. These results suggest complex cross communication between the two biological pathways in advanced stages of CHF.


2016 ◽  
Vol 74 (4) ◽  
pp. 149-158 ◽  
Author(s):  
Zeinab Sharifinasab ◽  
Mahdi Banaee ◽  
Mohammad Mohiseni ◽  
Ahmad Noori

Abstract The purpose of this study was to examine the effects of antioxidants, including vitamin C, chitosan or a combination of both, on oxidative stress markers in muscles, as edible tissues of fish, exposed to paraquat. Fish exposed to 0.02 mg/L paraquat for 21 days were fed different diets: a normal diet, a diet containing chitosan (1000 mg/kg diet), a diet with vitamin C (1000 mg/kg diet) or both vitamin C and chitosan. Oxidative stress markers, including the activity of catalase, total antioxidant and malondialdehyde (MDA), as well as biochemical parameters including the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), were measured in muscles. Fish exposure to paraquat increased LDH, CPK, catalase and MDA activity significantly, while it significantly decreased AST, ALT and AChE activity and total antioxidant capacity in muscles. Administration of vitamin C, combined with chitosan, to fish exposed to paraquat was effective in regulating AChE, AST, ALT, LDH, CPK and catalase activity. A significant increase in the total antioxidant status and a significant decrease in MDA levels were observed in fish fed chitosan-vitamin C complex. In conclusion, it is suggested that combined supplementation with vitamin C and chitosan may improve the detoxification system in the muscles of fish and protect common carp from paraquat toxicity.


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