scholarly journals Deletion of RasGRF1 Attenuated Interstitial Fibrosis in Streptozotocin-Induced Diabetic Cardiomyopathy in Mice through Affecting Inflammation and Oxidative Stress

2018 ◽  
Vol 19 (10) ◽  
pp. 3094 ◽  
Author(s):  
Tzu-Hsien Tsai ◽  
Cheng-Jei Lin ◽  
Sarah Chua ◽  
Sheng-Ying Chung ◽  
Shyh-Ming Chen ◽  
...  

Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1−/−) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1−/− mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1−/− mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1−/− mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1−/− mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

2015 ◽  
Vol 408 (1-2) ◽  
pp. 63-72 ◽  
Author(s):  
Suresh K. Gupta ◽  
Shirish Dongare ◽  
Rajani Mathur ◽  
Ipseeta Ray Mohanty ◽  
Sushma Srivastava ◽  
...  

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1263
Author(s):  
Karol Tejchman ◽  
Anita Sierocka ◽  
Katarzyna Kotfis ◽  
Maciej Kotowski ◽  
Barbara Dolegowska ◽  
...  

Ischemia-reperfusion injury (IRI) after renal transplantation is a complex biochemical process. The first component is an ischemic phase during kidney storage. The second is reperfusion, the main source of oxidative stress. This study aimed to analyze the activity of enzymes and concentrations of non-enzymatic compounds involved in the antioxidant defense mechanisms: glutathione (GSH), glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione transferase (GST), thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), measured in preservation fluid before transplantation of human kidneys (KTx) grafted from brain dead donors. The study group (N = 66) was divided according to the method of kidney storage: Group 1—hypothermic machine perfusion (HMP) in LifePort perfusion pump, n1 = 26, and Group 2—static cold storage (SCS), n2 = 40. The measurements of kidney function parameters, blood count, and adverse events were performed at constant time points during 7-day hospitalization and 3-month follow-up. Kidney perfusate in Group 2 was characterized by significantly more acidic pH (p < 0.0001), higher activity of GPX [U/mgHb] (p < 0.05) and higher concentration of MDA [μmol/L] (p < 0.05). There was a statistically significant improvement of kidney function and specific blood count alterations concerning storage method in repeated measures. There were aggregations of significant correlations (p < 0.05) between kidney function parameters after KTx and oxidative stress markers: diuresis & CAT, Na+ & CAT, K+ & GPX, urea & GR. There were aggregations of significant correlations (p < 0.05) between recipient blood count and oxidative stress markers: CAT & MON, SOD & WBC, SOD & MON. Study groups demonstrated differences concerning the method of kidney storage. A significant role of recipient’s gender, gender matching, preservation solution, and perfusate pH was not confirmed, however, basing on analyzed data, the well-established long-term beneficial impact of HMP on the outcome of transplanted kidneys might partially depend on the intensity of IRI ischemic phase and oxidative stress, reflected by the examined biomarkers.


F1000Research ◽  
2022 ◽  
Vol 10 ◽  
pp. 1161
Author(s):  
Mirasari Putri ◽  
Bening Mauliddina Rastiarsa ◽  
Raden Aliya T. M. Djajanagara ◽  
Ghaliby Ardhia Ramli ◽  
Neni Anggraeni ◽  
...  

Background: Sepsis causes several immunological and metabolic alterations that induce oxidative stress. The modulation of fatty acid-binding protein 4 (FABP4) has been shown to worsen this condition. Extract of cogon grass root (ECGR) contains flavonoids and isoeugenol compounds that exhibit anti-inflammatory and antioxidant properties. This study aimed to assess the effects of ECGR on FABP4 and oxidative stress–related factors in a sepsis mouse model. Methods: Twenty-nine male mice (Mus musculus) of the Deutsche Denken Yoken strain were divided into four groups: group 1, control; group 2, mice treated with 10 μL/kg body weight (BW) lipopolysaccharide (LPS); and groups 3 and 4, mice pre-treated with 90 and 115 mg/kg BW, respectively, and then treated with 10 μL/kg BW LPS for 14 d. Blood, liver, lymph, and cardiac tissue samples were collected and subjected to histological and complete blood examinations. Antioxidant (Glutathione peroxidase 3 (GPx3) and superoxide dismutase), FABP4 levels, and immune system-associated biomarker levels (TNF-α, IL-6 and IL-1β ) were measured. Results: Significant increases in platelet levels (p = 0.03), cardiomyocyte counts (p =0.004), and hepatocyte counts (p = 0.0004) were observed in group 4 compared with those in group 2. Conversely, compared with those in group 2, there were significant decreases in TNF-α expression in group 3 (p = 0.004), white pulp length and width in group 4 (p = 0.001), FABP4 levels in groups 3 and 4 (p = 0.015 and p = 0.012, respectively), lymphocyte counts in group 4 (p = 0.009), and monocyte counts (p = 0.000) and polymorphonuclear cell counts in the livers (p = 0.000) and hearts (p = 0.000) of groups 3 and 4. GPx3 activity was significantly higher in group 3 than in group 1 (p = 0.04). Conclusions: ECGR reduces FABP4 level and modulating oxidative stress markers in sepsis mouse model.


2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Ying Ann Chiao ◽  
Christine Light ◽  
Xiaojian Shi ◽  
Rong Tian ◽  
Junichi Sadoshima ◽  
...  

Diabetes is long linked to lowered NAD/NADH ratio, aka NAD redox imbalance, but its causal role to diabetic cardiomyopathy is not established. We used mouse models with latent decrease in cardiac NAD/NADH ratio (cardiac-specific Ndufs4-KO, cKO) and elevated cardiac NAD levels to directly test whether cardiac NAD redox imbalance accelerates diabetic cardiomyopathy. Control and cKO mice were subjected to 8-week T1D stress, and longitudinal cardiac function was measured by echocardiography. Accelerated declines in systolic and diastolic function were observed in T1D cKO mice. Insulin depletion and hyperglycemia were similar in T1D control and T1D cKO mice, and serum metabolomic analyses showed unchanged aqueous and lipid metabolite levels. These metabolite results suggested that T1D control and cKO hearts were stressed under similar diabetic conditions. Importantly, elevation of cardiac NAD levels to attenuate NAD redox imbalance mitigated the accelerated functional declines in T1D cKO hearts. The data from mouse models with manipulated NAD redox states suggested that NAD redox imbalance accelerates diabetic cardiomyopathy. Cardiac fibrosis levels were not different in T1D control and cKO hearts, while transcript levels of fibrotic genes, including Adamts proteinases, integrins, laminins, matrix metalloproteinases and collagens, also showed no difference. Therefore, the accelerated functional declines in T1D cKO hearts are not due to altered extracellular matrix environment, but are rather due to cardiomyocyte dysfunction. We next determined whether the accelerated cardiac dysfunction is mediated via protein acetylation and oxidative stress. NAD-dependent global protein acetylation and inhibitory acetylation of superoxide dismutase 2 were elevated in T1D cKO hearts. Inhibition of SOD2 concomitantly promoted elevation of protein oxidation levels in T1D cKO hearts. The results suggested that NAD redox balance-dependent protein acetylation regulates oxidative stress to promote diabetic cardiomyopathy.


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.


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