scholarly journals Assessment of the Dynamics of Oxidative Stress Indicators and Early Markers of Myocardial Damage and Dysfunction in Patients with Aggressive Lymphoproliferative Diseases During of Anticancer Therapy

Kardiologiia ◽  
2021 ◽  
Vol 60 (12) ◽  
pp. 76-82
Author(s):  
O. N. Antyufeeva ◽  
D. A. Budanova ◽  
I. S. Ilgisonis ◽  
I. Yu. Gadaev ◽  
O. V. Bochkarnikova ◽  
...  

Aim      To evaluate the dynamics of indexes of oxidative stress and markers of myocardial injury and dysfunction in patients with aggressive type lymphomas during the antitumor therapy.Material and methods  This study included 75 patients with lymphoproliferative diseases of aggressive type. The main group consisted of 53 patients who received one course of antitumor therapy during the study. The comparison group consisted of 22 patients who have not received any specific treatment so far. Troponin I (TnI), high-sensitivity troponin (hsTnI), heart-type fatty acid binding protein (Н-FAВР), N-terminal pro-brain natriuretic peptide (NT-prоBNP), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in patients of both groups at baseline, and in the main group, they were measured at 4 hours after administration of antitumor agents and on completion of the course. Functional status of the cardiovascular system was evaluated by electrocardiography in all patients at baseline and after the course of antitumor treatment and by echocardiography.Results The chemotherapy was associated with increased levels of NT-prоBNP, SOD, and MPO (30.670±15.367 vs. 52.309±25.718 pmo l/l; 1.61±0.135 vs. 1.74±0.193 U/ml; and 507.54±91.51 vs. 742.3±49.01 ng/ml, respectively). The study results indicated activation of oxidative stress on the background of the administered antitumor therapy, progressive myocardial dysfunction, and increased frequency of arrhythmic episodes.Conclusion      The study results allowed identifying NT-prоBNP, MPO, and SOD as important indexes for determining a patient group at high risk of cardiotoxicity during the antitumor treatment. 

2011 ◽  
Vol 111 (5) ◽  
pp. 1242-1248 ◽  
Author(s):  
Damien Vitiello ◽  
Julien Boissière ◽  
Grégory Doucende ◽  
Sandrine Gayrard ◽  
Anne Polge ◽  
...  

Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P < 0.001]. However, no differences in MDA were observed between groups. These data suggest that myocardial dysfunction observed after PSE was not due to β-adrenergic receptor desensitization but could be due to a signaling oxidative stress from the Nox enzyme.


2021 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  

Abstract Background: Sodium–glucose co-transporter 2 (SGLT2) inhibition reduces hyperglycaemia and has beneficial effects in heart failure. However, the effect of SGLT2 inhibition with empagliflozin on acute myocardial dysfunction after cardiac arrest (CA) remains unknown.Methods: Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 minutes after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. Results: Empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial contraction band necrosis, myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as myocardial expression of the 𝛽-hydroxy butyrate dehydrogenase 1. Together these metabolic changes were associated with an increase in cardiac ATP production.Conclusions: Empagliflozin favorably affects cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might be of benefit in patients with acute myocardial dysfunction after CA.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yunke Tan ◽  
Kai Yu ◽  
Lian Liang ◽  
Yuanshan Liu ◽  
Fengqing Song ◽  
...  

Empagliflozin is a newly developed antidiabetic drug to reduce hyperglycaemia by highly selective inhibition of sodium–glucose co-transporter 2. Hyperglycaemia is commonly seen in patients after cardiac arrest (CA) and is associated with worse outcomes. In this study, we examined the effects of empagliflozin on cardiac function in rats with myocardial dysfunction after CA. Non-diabetic male Sprague–Dawley rats underwent ventricular fibrillation to induce CA, or sham surgery. Rats received 10 mg/kg of empagliflozin or vehicle at 10 min after return of spontaneous circulation by intraperitoneal injection. Cardiac function was assessed by echocardiography, histological analysis, molecular markers of myocardial injury, oxidative stress, mitochondrial ultrastructural integrity and metabolism. We found that empagliflozin did not influence heart rate and blood pressure, but left ventricular function and survival time were significantly higher in the empagliflozin treated group compared to the group treated with vehicle. Empagliflozin also reduced myocardial fibrosis, serum cardiac troponin I levels and myocardial oxidative stress after CA. Moreover, empagliflozin maintained the structural integrity of myocardial mitochondria and increased mitochondrial activity after CA. In addition, empagliflozin increased circulating and myocardial ketone levels as well as heart β-hydroxy butyrate dehydrogenase 1 protein expression. Together, these metabolic changes were associated with an increase in cardiac energy metabolism. Therefore, empagliflozin favorably affected cardiac function in non-diabetic rats with acute myocardial dysfunction after CA, associated with reducing glucose levels and increasing ketone body oxidized metabolism. Our data suggest that empagliflozin might benefit patients with myocardial dysfunction after CA.


Kardiologiia ◽  
2020 ◽  
Vol 60 (11) ◽  
pp. 49-56
Author(s):  
D. A. Budanova ◽  
O. N. Antyufeeva ◽  
I. S. Ilgisonis ◽  
I. Ya. Sokolova ◽  
Yu. N. Belenkov ◽  
...  

Aim      To study changes in markers for myocardial direct injury and dysfunction and endothelial dysfunction (ED) indexes in patients with indolent lymphoma during the antitumor treatment.Material and methods  Current antitumor therapy for lymphoma is often associated with cardio- and vasculotoxicity, studying of which is a relevant scientific direction. Markers for myocardial direct injury and dysfunction and ED indexes were studied in patients with indolent lymphomas receiving polychemotherapy (PCT). The study included 77 patients with newly diagnosed indolent type lymphoma. The main group (n=52): mean age, 63.4±2.8 years, 15 (28.8 %) men who had received one course of PCT. The comparison group (n=25): mean age, 61.8±3.7 years, 8 (32 %) men who had not received PCT. Troponin I (TnI), high-sensitivity troponin I (hs-сTnI), heart-type fatty acid binding protein (h-FAВР), and N-terminal pro-B-type natriuretic peptide (NT-prоBNP) were measured in patients of both groups. ED was evaluated by measuring the level of vascular cell adhesion molecule (VCAM) and by assessing the structure and function condition of small blood vessels using photoplethysmography. In both groups, the study parameters were determined at the start of the study (T1) and following the PCT course in the main group; if the PCT schedule included anthracycline antibiotics, the second point (T2) was assessed at 6 h following the drug administration.Results In both groups, the level of NT-proBNP was increased. This increase was significantly more pronounced in the comparison group (49.896±23.228 vs 20.877±8.534 pmol/l, respectively, p=0.011) whereas a tendency to its increase was observed after the PCT course. Before the start of the treatment, laboratory and instrumental signs of ED were noticed: the level of VCAM was 4951±1297 and 3225±757 ng/ml in the comparison group and the main group, respectively (р=0.246); reflection index was <1.8 in 23 (44.2%) patients of the main group and in 16 (64%) patients of the comparison group (р=0.098). During the PTC course, the endothelial function significantly improved; the level of VCAM decreased by 748 ng/ml (p=0.016), which was associated with significant decreases in erythrocyte sedimentation rate by 2.71 mm/h (р=0.027) and lactate dehydrogenase level by 62.38 U/l (р=0.026). Statistically significant decreases in other inflammatory markers (alpha-2-globulin, fibrinogen, C-reactive protein, neutrophil count) were not observed.Conclusion      The level of NT-proBNP showed the highest sensitivity in assessing the cardiotoxic effect of PCT. The dynamics of VCAM level suggested a possible role of the disease itself in the development of ED in this patient group. 


2018 ◽  
Vol 2 (S1) ◽  
pp. e000127
Author(s):  
Kushali Tanna ◽  
K M Mehariya ◽  
Suchita Munsi ◽  
Charul Pujani

Aims and Objectives: To study an incidence of myocardial dysfunction in neonates admitted with perinatal asphyxia, to find out its correlation with severity of birth asphyxia and its outcome. Methods: This prospective study was conducted among 40 term neonates admitted in NICU of Civil Hospital Ahmedabad who had suffered with perinatal asphyxia (defined by WHO ), resuscitated as per NRP guidelines-2015 including both intramural and extramural admissions and who developed to hypoxic ischemic encephalopathy as defined by Levene staging. Neonates with congenital heart diseases, major central nervous system malformations and neonatal sepsis were excluded. Myocardial involvement was assessed by clinical evaluation, ECG, Creatinine Kinase Total (25-200IU/L), CK-MB (0-25IU/L) and Troponin I (0-0.03ug/L) measurements. Results: Among 40 cases, 10(25%) neonates had moderate birth asphyxia while 30(75%) had severe birth asphyxia. Respiratory distress was observed in 34(77.5%), poor spontaneous respiration 4(10%),shock in 14(35%),CCF 19(47.5%) while ECG was abnormal in 30(76.7%). Serum levels of CPK Total, CPK- MB and Troponin I were raised in 34(85%), 32(80%) and 28 (70%) neonates, respectively.  Conclusion: There was a direct correlation between ECG changes and enzymatic levels which showed increasing abnormalities with increasing with severity of HIE.  


2020 ◽  
Vol 16 (7) ◽  
pp. 1083-1102
Author(s):  
Mohamed A. Shreadah ◽  
Nehad M.A. El Moneam ◽  
Samy A. El-Assar ◽  
Asmaa Nabil-Adam

Background: Aspergillus Versicolor is a marine-derived fungus isolated from Hyrtios Erectus Red Sea sponge. Methods: The aim of this study was to carry out a pharmacological screening and investigation for the in vitro biological activity (antioxidant, cholinergic, antidiabetic and anticancer) of Aspergillus Versicolor crude extract’s active compounds by using different qualitative and quantitative methods. Results: The present study results showed that Aspergillus Versicolor crude extracts contain 0.6 mg total phenolic/mg crude extract. Aspergillus Versicolor also showed a potent antioxidative capacity by decreasing the oxidation of ABTS. The anticancer and inhibitory effects of Aspergillus Versicolor crude extracts on PTK and SHKI were found to be 75.29 % and 80.76%; respectively. The AChE inhibitory assay revealed that Aspergillus Versicolor extracts had an inhibitory percentage of 86.67%. Furthermore, the anti-inflammatory activity using COX1, COX2, TNF, and IL6 was 77.32, 85.21 %, 59.83%, and 56.15%; respectively. Additionally, the anti-viral effect using reverse transcriptase enzyme showed high antiviral activity with 92.10 %. Conclusion: The current study confirmed that the Aspergillus versicolor crude extract and its active constituents showed strong effects on diminishing the oxidative stress, neurodegenerative damage, antiinflammatory, anti-cancer and anti-viral, suggesting their beneficial role as a promising fermented product in the treatment of cancer, oxidative stress, Alzheimer's, anti-inflammatory and anti-viral diseases.


2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Nermin Isik ◽  
Ozlem Derinbay Ekici ◽  
Ceylan Ilhan ◽  
Devran Coskun

 Background: Theileriosis is a tick-borne disease caused by Theileria strains of the protozoan species. Buparvaquone is the mostly preferred drug in the treatment theileriosis, while it is safety in sheep, has not been detailed investigated. It has been hypothesized that buparvaquone may show side effects and these effects may be defined some parameters measured from blood in sheep when it is used at the recommended dose and duration. The aim of this research was to determine the effect of buparvaquone on the blood oxidative status, cardiac, hepatic and renal damage and bone marrow function markers.Materials, Methods & Results: In this study, ten adult (> 2 years) Akkaraman rams were used. Healthy rams were placed in paddocks, provided water ad libitum, and fed with appropriate rations during the experiment. Buparvaquone was ad­ministered at the dose of 2.5 mg/kg (IM) intramuscularly twice at 3-day intervals. Blood samples were obtained before (0. h, Control) and after drug administration at 0.25, 0.5, 1, 2, 3, 4 and 5 days. The blood samples were transferred to gel tubes, and the sera were removed (2000 g, 15 min). During the study, the heart rate, respiratory rate, and body temperature were measured at each sampling time. In addition, the animals were clinically observed. Plasma oxidative status mark­ers (Malondialdehyde, total antioxidant status, catalase, glutathione peroxidase, superoxide dismutase), serum cardiac (Troponin I, creatine kinase-MBmass, lactate dehydrogenase), hepatic (Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, globulin) and renal (Creatinine, blood urea nitrogen) damage markers and hemogram values (white blood cell, red blood cell, platelet, hemogram, hematocrit) were measured. Buparvaquone caused statistically significantly (P < 0.05) increases in the troponin I and blood urea nitrogen levels and fluctuations in alkaline phosphatase activity, but there was no any statistically significance difference determined in the other parameters.Discussion: In this study, buparvaquone was administered two times at a dose of 2.5 mg/kg (IM) at 3-day intervals. Al­though the result was not statistically significant (P > 0.05), it was determined that buparvaquone gradually increased the levels of the main oxidative stress marker, MDA, by approximately 2.8 fold. CAT and GPX levels were also found to have decreased by 2.2 fold. Buparvaquone may cause lipid peroxidation by producing free radicals. Some other antiprotozoal drugs may affect the oxidative status and may increase MDA level and decrease SOD level. In this study, MDA, which is an indicator of lipid peroxidation in vivo, was used to partially detect developing lipid peroxidation. Changes in the levels of reduced GPX and CAT enzymes could be attributed to their use in mediating the hydrogen peroxide detoxification mechanisms. The absence of significant changes in the TAS levels in this study suggests that buparvaquone may partially induce oxidative stress by producing hydrogen peroxide, but no significant changes occurred in the oxidative stress level because of the high antioxidant capacity of sheep. In this study, buparvaquone caused a statistically significant increase (P < 0.05) in the level of Tn-I, which is a marker of specific cardiac damage (P < 0.05), whereas there was no statistically (P > 0.05) significant increase in CK-MBmass. Tn-I and CK-MB levels, which are used to define heart damage in humans, have been successfully used to determine heart damage in sheep. In this research study, the statistically significant increases in Tn-I but not CK-MBmass levels could be considered indicative of mild cardiac damage.Keywords: ram, buparvaquone, safety.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1453
Author(s):  
Haoran Wang ◽  
Jianhua Wei ◽  
Hong Jiang ◽  
Ye Zhang ◽  
Caina Jiang ◽  
...  

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a–6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 110
Author(s):  
Yifei Wang ◽  
Yasuharu Shinoda ◽  
An Cheng ◽  
Ichiro Kawahata ◽  
Kohji Fukunaga

The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.


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