Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction

2007 ◽  
Vol 112 (4) ◽  
pp. 241-250 ◽  
Author(s):  
Jorge Berlanga ◽  
Danay Cibrian ◽  
Luis Guevara ◽  
Heberto Dominguez ◽  
Jose S. Alba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Infarct Size ◽  
Myocardial Injury ◽  
Myocardial Infarct Size ◽  
Oxidative Stress Markers ◽  
Left Circumflex Artery ◽  
Stress Markers ◽  
Creatine Kinase Mb ◽  
Igf I

Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period. Animals were screened clinically before surgery and assigned randomly to receive either GHRP6 (400 μg/kg of body weight) or normal saline. Hearts were processed, and the area at risk and the infarct size were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels and pathological Q-wave-affected leads were analysed and compared. Evaluation of the myocardial effect of GHRP6 also included quantitative histopathology, local IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6 treatment did not have any influence on mortality during surgery associated with rhythm and conductance disturbances during ischaemia. Infarct mass and thickness were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01). More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of oxidative stress markers suggested that GHRP6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by GHRP6 treatment compared with the increase induced by the ischaemic episode in relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits antioxidant effects which may partially contribute to reduce myocardial ischaemic damage.

scholarly journals Remote Limb Ischaemic Postconditioning Protects Against Myocardial Ischaemia/Reperfusion Injury in Mice: Activation of JAK/STAT3-Mediated Nrf2-Antioxidant Signalling

2017 ◽  
Vol 43 (3) ◽  
pp. 1140-1151 ◽  
Author(s):  
Sumin Gao ◽  
Leyun Zhan ◽  
Zhengchao Yang ◽  
Ruili Shi ◽  
Haobo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Ischaemia ◽  
Nuclear Translocation ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Enzyme Release ◽  
Ischaemia Reperfusion ◽  
Myocardial Oxidative Stress ◽  
Creatine Kinase Mb

Background: This study aimed to evaluate the protective effect and mechanisms of remote limb ischaemic postconditioning (RIPostC) against myocardial ischaemia/reperfusion (IR) injury. Methods: Male mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. RIPostC was achieved by three cycles of 5 min of ischaemia and 5 min of reperfusion in the left hind limb at the start of the reperfusion period. After 2 h of cardiac reperfusion, myocardial infarct size, cardiac enzyme release, apoptosis and oxidative stress were assessed. Protein expression and phosphorylation were measured by Western blotting. Results: RIPostC significantly decreased cardiac IR injury, as reflected by reduced infarct size and cellular apoptosis (22.9 ± 3.3% vs 40.9 ± 6.2% and 13.4% ± 3.1% vs 26.2% ± 3.1%, respectively, both P < 0.01) as well as plasma creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) release (21.97 ± 4.08 vs 35.86 ± 2.91 ng/ml and 6.17 ± 0.58 vs 8.37 ± 0.89 U/ml, respectively, both P < 0.01) compared with the IR group. RIPostC significantly increased the phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.01). In addition, RIPostC elevated the nuclear translocation of Nrf2 and the expression of HO-1 and reduced myocardial oxidative stress (P < 0.05). Interestingly, pretreatment with the JAK/STAT3 inhibitor AG490 blocked the cardioprotective effect of RIPostC accompanied by decreased phosphorylation of myocardial STAT3, Akt and eNOS (P < 0.05), decreased nuclear translocation of Nrf2 and expression of HO-1, as well as increased oxidative stress (P < 0.05). Conclusion: RIPostC attenuates apoptosis and protects against myocardial IR injury, possibly through the activation of JAK/STAT3-mediated Nrf2-antioxidant signalling.

Oxidative stress markers in women with polycystic ovary syndrome without insulin resistance

2018 ◽  
Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oxidative Stress Markers ◽  
Ovary Syndrome ◽  
Stress Markers

Comparison of Salivary Antioxidants and Oxidative Stress Status in Gestational Diabetes Mellitus and Healthy Pregnant Women

2020 ◽  
Vol 20 ◽  
Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Shima Fathi ◽  
Mohammad Taghi Goodarzi ◽  
Shiva Borzouei ◽  
Jalal Poorolajal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Oxidative Stress Markers ◽  
Blood Samples ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Total Oxidative Stress ◽  
And Oxidative Stress

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.

Evaluation of Salivary Antioxidants and Oxidative Stress Markers in Type 2 Diabetes Mellitus: A Retrospective Cohort Study

2020 ◽  
Vol 20 (4) ◽  
pp. 584-590 ◽  
Author(s):  
Shima Fathi ◽  
Shiva Borzouei ◽  
Mohammad Taghi Goodarzi ◽  
Jalal Poorolajal ◽  
Fatemeh Ahmadi-Motamayel
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Type 2 Dm ◽  
Patients With Diabetes ◽  
The Difference ◽  
And Oxidative Stress

Background: Diabetes Mellitus (DM) is a progressive metabolic disorder. Objective: The aim of this study was to investigate the relationship between antioxidant and oxidative stress markers in the saliva of patients with type 2 DM and a healthy control group. Methods: In this study, 20 patients with diabetes and 20 healthy individuals were evaluated. Salivary antioxidants markers consisted of total antioxidant capacity (TAC), uric acid (UA), peroxidase and catalase. Oxidative stress markers included total oxidant status (TOS), malondealdehyde (MDA) and total thiol (SH). Sialochemical analysis was performed with spectrophotometric assay. All the statistical analyses were conducted using STATA software. Results: TAC decreased significantly in patients with diabetes. Although salivary UA and peroxidase were lower in patients with diabetes compared to the control group, the difference was not significant. Salivary catalase in patients with diabetes was significantly lower than that in the control group. MDA and TOS exhibited significantly higher levels in type 2 DM. SH levels were slightly higher in DM. Conclusions: According to the results of the present study, there were some changes in the salivary levels of some antioxidants and oxidative stress markers in patients with type 2 DM and could be measured as an indicator of serum changes..

Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers

2021 ◽  
Vol 65 ◽  
pp. 126711
Author(s):  
Barbara Witt ◽  
Michael Stiboller ◽  
Stefanie Raschke ◽  
Sharleen Friese ◽  
Franziska Ebert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Excess Copper

scholarly journals Hydralazine protects the heart against acute ischaemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission

2021 ◽  
Author(s):  
Siavash Beikoghli Kalkhoran ◽  
Janos Kriston-Vizi ◽  
Sauri Hernandez-Resendiz ◽  
Gustavo E Crespo-Avilan ◽  
Ayeshah A Rosdah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Mitochondrial Fission ◽  
Vehicle Control ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Pre Treatment ◽  
Apoptotic Effects

Abstract Aims Genetic and pharmacological inhibition of mitochondrial fission induced by acute myocardial ischaemia/reperfusion injury (IRI) has been shown to reduce myocardial infarct size. The clinically used anti-hypertensive and heart failure medication, hydralazine, is known to have anti-oxidant and anti-apoptotic effects. Here, we investigated whether hydralazine confers acute cardioprotection by inhibiting Drp1-mediated mitochondrial fission. Methods and results Pre-treatment with hydralazine was shown to inhibit both mitochondrial fission and mitochondrial membrane depolarisation induced by oxidative stress in HeLa cells. In mouse embryonic fibroblasts (MEFs), pre-treatment with hydralazine attenuated mitochondrial fission and cell death induced by oxidative stress, but this effect was absent in MEFs deficient in the mitochondrial fission protein, Drp1. Molecular docking and surface plasmon resonance studies demonstrated binding of hydralazine to the GTPase domain of the mitochondrial fission protein, Drp1 (KD 8.6±1.0 µM), and inhibition of Drp1 GTPase activity in a dose-dependent manner. In isolated adult murine cardiomyocytes subjected to simulated IRI, hydralazine inhibited mitochondrial fission, preserved mitochondrial fusion events, and reduced cardiomyocyte death (hydralazine 24.7±2.5% vs. control 34.1±1.5%, P=0.0012). In ex vivo perfused murine hearts subjected to acute IRI, pre-treatment with hydralazine reduced myocardial infarct size (as % left ventricle: hydralazine 29.6±6.5% vs. vehicle control 54.1±4.9%, P=0.0083), and in the murine heart subjected to in vivo IRI, the administration of hydralazine at reperfusion, decreased myocardial infarct size (as % area-at-risk: hydralazine 28.9±3.0% vs. vehicle control 58.2±3.8%, P&lt;0.001). Conclusion We show that, in addition to its antioxidant and anti-apoptotic effects, hydralazine, confers acute cardioprotection by inhibiting IRI-induced mitochondrial fission, raising the possibility of repurposing hydralazine as a novel cardioprotective therapy for improving post-infarction outcomes.

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