scholarly journals Glutathione peroxidase in acute coronary syndromes

2021 ◽  
Author(s):  
◽  
Ana Simone Holley

<p>Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are among the primary antioxidant enzymes that scavenge reactive oxygen species in the blood (ROS), thereby protecting against high levels of oxidative stress. The consequences of oxidative stress include cellular injury and tissue damage. High levels of oxidative stress have been implicated in the pathogenesis of acute coronary syndromes (ACS), however large clinical trials involving dietary antioxidant supplements have not shown a reduction in the rate of major adverse cardiovascular events (MACE).  In a cohort of 262 ACS patients we examined the relationship between GPx activity, SOD activity and MACE. Patients with MACE were found to have significantly lower levels of GPx activity than those without MACE, whereas SOD activity did not differ between the groups. Furthermore, dividing the patients into quartiles corresponding to levels of GPx activity demonstrated significantly higher rates of MACE in the lower quartile of GPx activity compared to the highest quartile.  Previous studies have demonstrated that deficiencies in GPx activity are associated with vascular dysfunction and platelet-dependent thrombosis, leading to the hypothesis that low levels of GPx activity would be associated with increased levels of platelet reactivity. In 51 ACS patients we did not observe a significant relationship between these two parameters, however we did demonstrate that increasing levels of GPx activity was associated with lower levels of ROS. ROS measures were based on the response of the platelets to addition of exogenous nitric oxide. Such an inverse relationship between GPx activity and levels of ROS is consistent with the view that GPx activity may play an important role in an ACS by reducing ROS-mediated damage, thereby protecting against MACE.  We examined levels of GPx activity, protein concentration and mRNA expression across populations of ACS patients, stable coronary disease patients and healthy subjects. Cardiovascular risk factors thought to influence levels of GPx activity were controlled for in all three cohorts. These studies demonstrated that GPx activity, protein and mRNA levels were significantly elevated in the ACS patients compared to the stable coronary disease patients and healthy subjects. Oxidised low-density lipoprotein (oxLDL), a widely used marker of oxidative stress, was also significantly elevated in the ACS patients compared to the other two cohorts.  In a study examining the temporal changes in GPx activity in the acute phase of an ACS, GPx activity was found to be highly dynamic, with no consistent single time point that identified when peak activity occurred. In the majority of patients, levels of oxLDL were found to peak prior to, or at the same time, as peak GPx activity, suggesting that GPx activity was modulated by changes in oxidative stress.  In conclusion, the elevated levels of GPx activity observed in ACS patients were found to be highly dynamic throughout an ACS event. However those with lower levels of GPx activity have an increased risk of adverse clinical outcomes that may be due to an inadequate defence against levels of ROS. Whether these patients can be accurately identified and targeted with an appropriate therapeutic intervention warrants further investigation.</p>

2021 ◽  
Author(s):  
◽  
Ana Simone Holley

<p>Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are among the primary antioxidant enzymes that scavenge reactive oxygen species in the blood (ROS), thereby protecting against high levels of oxidative stress. The consequences of oxidative stress include cellular injury and tissue damage. High levels of oxidative stress have been implicated in the pathogenesis of acute coronary syndromes (ACS), however large clinical trials involving dietary antioxidant supplements have not shown a reduction in the rate of major adverse cardiovascular events (MACE).  In a cohort of 262 ACS patients we examined the relationship between GPx activity, SOD activity and MACE. Patients with MACE were found to have significantly lower levels of GPx activity than those without MACE, whereas SOD activity did not differ between the groups. Furthermore, dividing the patients into quartiles corresponding to levels of GPx activity demonstrated significantly higher rates of MACE in the lower quartile of GPx activity compared to the highest quartile.  Previous studies have demonstrated that deficiencies in GPx activity are associated with vascular dysfunction and platelet-dependent thrombosis, leading to the hypothesis that low levels of GPx activity would be associated with increased levels of platelet reactivity. In 51 ACS patients we did not observe a significant relationship between these two parameters, however we did demonstrate that increasing levels of GPx activity was associated with lower levels of ROS. ROS measures were based on the response of the platelets to addition of exogenous nitric oxide. Such an inverse relationship between GPx activity and levels of ROS is consistent with the view that GPx activity may play an important role in an ACS by reducing ROS-mediated damage, thereby protecting against MACE.  We examined levels of GPx activity, protein concentration and mRNA expression across populations of ACS patients, stable coronary disease patients and healthy subjects. Cardiovascular risk factors thought to influence levels of GPx activity were controlled for in all three cohorts. These studies demonstrated that GPx activity, protein and mRNA levels were significantly elevated in the ACS patients compared to the stable coronary disease patients and healthy subjects. Oxidised low-density lipoprotein (oxLDL), a widely used marker of oxidative stress, was also significantly elevated in the ACS patients compared to the other two cohorts.  In a study examining the temporal changes in GPx activity in the acute phase of an ACS, GPx activity was found to be highly dynamic, with no consistent single time point that identified when peak activity occurred. In the majority of patients, levels of oxLDL were found to peak prior to, or at the same time, as peak GPx activity, suggesting that GPx activity was modulated by changes in oxidative stress.  In conclusion, the elevated levels of GPx activity observed in ACS patients were found to be highly dynamic throughout an ACS event. However those with lower levels of GPx activity have an increased risk of adverse clinical outcomes that may be due to an inadequate defence against levels of ROS. Whether these patients can be accurately identified and targeted with an appropriate therapeutic intervention warrants further investigation.</p>


2017 ◽  
Vol 65 (5) ◽  
pp. 919-925 ◽  
Author(s):  
Ana Holley ◽  
Janet Pitman ◽  
John Miller ◽  
Scott Harding ◽  
Peter Larsen

High levels of the antioxidant enzyme, glutathione peroxidase (GPx), have been associated with improved outcomes following acute coronary syndromes (ACS), suggesting a protective role. How GPx levels are altered with coronary disease is not clearly established. This study examined GPx activity, protein, and mRNA levels in healthy controls, patients with stable coronary artery disease (CAD), and patients with ACS. We studied 20 individuals from each of the healthy control, stable CAD, and ACS groups. GPx activity and protein levels, along with oxidized low-density lipoprotein (oxLDL) were assayed in plasma. GPx mRNA levels from whole blood were quantified using real-time PCR. Levels of GPx activity in the plasma were higher in ACS (109±7.7 U/mL) compared with patients with stable CAD (95.2±16.4 U/mL, p<0.01) and healthy controls (87.6±8.3 U/mL, p<0.001). Plasma GPx protein levels were also elevated in ACS (21.6±9.5 µg/mL) compared with patients with stable CAD (16.5±2.8 µg/mL, p<0.05) and healthy controls (16.3±5.3 µg/mL, p<0.05). Levels ofGPX1,GPX3, andGPX4mRNA were significantly higher in the patients with ACS. Levels of oxLDL were also significantly higher in patients with ACS (61.9±22.2 U/L) than in patients with stable CAD (47.8±10.4 U/L, p<0.05) and healthy controls (48.9±11.9 U/L, p<0.05). Levels of oxLDL, GPx activity, protein, and mRNA are all significantly higher in patients with ACS compared with patients with stable CAD and healthy controls. These findings suggest that GPx may be upregulated in response to a change in oxidative stress during an ACS.


2018 ◽  
Vol 27 (4) ◽  
pp. 223-8 ◽  
Author(s):  
Citra Praditi ◽  
Ani R. Prijanti ◽  
Sri W.A. Jusman ◽  
Mohamad Sadikin

Background: Lymphocytes activated by immunization must increase their metabolism to meet the energy requirements for mitosis, differentiation, and protein synthesis, which may subject the cell to conditions of relative hypoxia and oxidative stress. This study was conducted to investigate the increase in the levels of transcription factors involved in both conditions.Methods: Male Balb/c mice were divided into the following four groups, each consisting of six animals: the control and three experimental groups. The experimental groups were immunized by injection of 0.2 ml of 2% sheep red blood cells (SRBC) suspended in phosphate-buffered saline (PBS). Lymphocytes were harvested from the spleens of each group at time intervals of 24-, 48-, and 72-h post-immunization. The buffy coat from splenocytes was separated using Ficoll Histopaque as the medium. The lymphocytes were separated from adherent cells by incubating the purified splenocytes in microtubes for 2-h. Cells were lysed by three freeze–thaw cycles (−80°C and 37°C) and used to analyze the levels of HIF-1α and HIF-2α (mRNA and protein), Nrf2 (protein), and glutathione peroxidase (GPx) activity.Results: The treatment caused an increase in GPx activity and HIF-1α protein concentration 24-h post-immunization, whereas the HIF-1α mRNA levels remained static. Elevated Nrf2 protein levels were detected within 48-h after treatment. Meanwhile, the HIF-2α mRNA and protein levels increased within72-h after immunization.Conclusion: Immunization with SRBC suspension induced relative hypoxia, elevated reactive oxygen species (ROS), and oxidative stress in the lymphocytes as indicated by the increase in both HIF-1α and HIF-2α protein and mRNA levels, GPx activity, and Nrf2 protein levels.


1998 ◽  
Vol 79 (3) ◽  
pp. 305-309 ◽  
Author(s):  
D. A. Adelekan ◽  
D. I. Thurnham

Riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. The objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (EC1.11.1.9; GPx) and superoxide dismutase (EC1.15.1.1; SOD) in rats infected withPlasmodium bergheimalaria. Riboflavin in its co-enzyme form, FAD, is required by glutathione reductase (EC1.6.4.1) to regenerate GSH and GSH is an important cellular antioxidant both in its own right and also as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for 8 weeks before intraperitoneal injection of 1 × 106P. bergheiparasites. Control animals were weight-matched to the respective riboflavin-deficient group. At 10d post-infection, parasite counts were higher in the weight-matched control group than the riboflavin-deficient group (P= 0.004). GPx activity was higher in erythrocytes of rats parasitized withP. bergheithan comparable non-infected rats regardless of riboflavin status (P< 0.05). As mature erythrocytes do not synthesize new protein, the higher GPx activities were probably due to the presence of the parasite protein. In erythrocytes from riboflavin-deficient rats, GPx activity tended to be lower than in those rats fed on diets adequate in riboflavin (weight-matched controls) whether parasitized or not, but the difference was not significant. Neither riboflavin deficiency nor malaria had any effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency has no marked effect on erythrocyte GPx or SOD activity in the rat.


2020 ◽  
Vol 9 (40) ◽  
pp. 2970-2975
Author(s):  
Rohit John Chaudhary ◽  
Bharti Kwatra Uppal

BACKGROUND Severe oxidative stress has been reported in TB patients because of infection associated with malnutrition and poor immunity. Mycobacteria can induce reactive oxygen species (ROS) production by activating phagocytes, and enhanced ROS production may promote tissue injury and inflammation. We wanted to compare the effect of antioxidant administration in the outcome of ATT treatment between the test and the control group. METHODS This perspective study was conducted in the Departments of Biochemistry and Chest Medicine, CMC & Hospital. Hundred patients (fifty controls and fifty tests) who were diagnosed as pulmonary tuberculosis and started on DOT therapy under RNTCP during this period were included in the study. Each participant in the study was subjected to the following test at the first visit, 2nd month and 6th month follow up (biochemical markers Nitric oxide, SOD, Glutathione Peroxidase and Vitamin E levels). Statistical analysis was done using SPSS version. RESULTS The results were based on four categories (male / female, alcoholic / non-alcoholic, smoker / non-smoker, and younger / older age group). Females had responded better with greater fall in percentage of nitric oxide values (69 %) than males (64.1 %). The mean of SOD activity (277.5 + / - 31.5) was more in smokers than non-smokers (261.3 + / - 36.0) & percentage fall of nitric oxide in smokers (65 %) & non-smokers (67 %). In alcoholics the percentage fall of nitric oxide (68.3 %) was higher with more SOD activity (Mean 278.7 + / - 27.6) than non-alcoholics (Mean 256 + / - 38.0) indicating a positive correlation of smoking & alcoholism with tuberculosis. Younger age group responded better with more fall in the percentage of nitric oxide (67 %) & mean SOD activity (265.8 + / - 30.1) than older age group. CONCLUSIONS Antioxidant supplementation reduces oxidative stress, improves the effectiveness of ATT therapy, and thus helps in improving the outcome in pulmonary tuberculosis. KEY WORDS Pulmonary TB, ATT (Anti-Tubercular Treatment), Antioxidants & Free Radicals


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Harshi Prasadini Gunawardena ◽  
Renuka Silva ◽  
Ramiah Sivakanesan ◽  
Pathmasiri Ranasinghe ◽  
Prasad Katulanda

Glycaemic control is the main focus of managing diabetes and its complications. Hyperglycaemia induces oxidative stress favouring cellular damage and subsequent diabetic complications. The present study was conducted to compare the plasma total antioxidant capacity (TAC) and individual antioxidant marker antioxidant status of type 2 diabetics (T2D) with good ((+) GC) and poor ((-) GC) glycaemic control with prediabetic (PDM) and normoglycaemic (NG) individuals. T2D (n=147), PDM (n=47), and NGC (n=106) were recruited as subjects. T2D and PDM had lower plasma TAG than NG subjects. T2D and PDM had significantly higher GPx activity and plasma MDA concentrations than NG. PDM showed the highest SOD activity. T2D (-) GC showed significantly elevated GPx activity and higher MDA level and significantly lower SOD activity among all study groups. Lower plasma TAC and higher plasma MDA indicate the presence of oxidative stress in T2D and PDM. Elevated GPx activity in T2D, PDM, and particularly in T2D (-) GC suggests a compensatory response to counteract excess lipid peroxidation in the hyperglycaemic state. Decline in SOD activity advocates the presence of glycation and excess lipid peroxidation in T2D.


Foods ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 455
Author(s):  
Lee ◽  
Hur

This study was conducted to determine the effect of beef peptide extract on oxidative stress in the brains of spontaneously hypertensive rats (SHRs). A 3-kDa peptide extract was obtained from beef myofibrillar protein using alkaline-AK (AK3K). Oxidative stress in SHR brains was measured by assessing malondialdehyde (MDA) and reactive oxygen species (ROS) concentrations and superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activity. The SHR brains treated with the AK3K peptide extract (400 mg/kg body weight, AK3K400) showed a significant decrease in MDA and ROS contents by 0.33 and 23.92 μM, respectively (p < 0.05) compared to the control. The SOD activity for AK3K400 was 61.26%, around 20% higher than the control. Furthermore, the SHRs treated with the AK3K peptide extract showed results similar to those obtained using captopril, a hypertension drug, except for the MDA level. The study demonstrates that the beef peptide extract inhibits the generation of oxidative stress in the SHR brain and could possibly be used for neuronal hypertension therapy.


Author(s):  
Towseef Amin Rafeeqi ◽  
Farhat Jabeen ◽  
M A Waheed ◽  
Gulam Mohammed Husain ◽  
Alokananda Chakraborthy

AbstractBackgroundVitiligo, a skin disorder is viewed as a multifactorial process with major role of reactive oxygen species in concert to destroy or incapacitate melanocytes. In Unani system of medicine the treatment of Bars (Vitiligo) starts with removal of harmful materials from the body with Munzij and Mushil (MM), a poly herbal Unani formulation.MethodsHerein, oxidative stress related parameters as MDA, SOD, GPx and CAT have been estimated in the 21 clinically diagnosed Vitiligo in-patients and subsequently these parameters were evaluated during and after administration of MM therapy and compared with 21 healthy subjects.ResultsThere was significant difference in the parameters viz., SOD (p<0.001) and CAT (p<0.005) activity at the baseline with no statistical significant difference in MDA and GPx activity among Vitiligo subjects and controls. After MM therapy there was no statistical significant difference among the values of these parameters in Vitiligo subjects.ConclusionsThe results suggest that there is imbalance in the oxidant-antioxidant status of Vitiligo subjects and the MM therapy is not found to significantly change the levels of oxidative stress related parameters.


2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mahmoud A. Ali ◽  
Hassan Abu Damir ◽  
Osman M. Ali ◽  
Naheed Amir ◽  
Saeed Tariq ◽  
...  

Abstract Background Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression. Results The cytokines IL-1β and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days. Conclusions Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.


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