Cardiac Thiobarbituric Acid Reactive Substances Research Articles

The protective effect of rivaroxaban with or without aspirin on inflammation, oxidative stress, and platelet reactivity in isoproterenol-induced cardiac injury in rats.

Coronary artery diseases are principal sources of mortality and disability in global human population. Progressively, rivaroxaban is being evaluated for the prevention of atherosclerotic thrombi, particularly with anti-platelet agents. Hence, the current report aimed to investigate the cardioprotective effect of rivaroxaban on isoproterenol (ISO)-induced cardiac injury model in rats and the possible synergistic effect when combined with aspirin. Male Wistar rats were randomly assigned into five different groups. Cardiac injury was induced by subcutaneous injection of ISO (85mg/kg) for 2 consecutive days. Rat tail bleeding time was performed prior to sacrifice. Cardiac enzymes, platelet activity, inflammatory, and oxidative stress biomarkers levels were measured using enzyme-linked immunoassay (ELISA). Pre-administration of rivaroxaban alone and on combination with aspirin prevented ISO-induced increase in cardiac thiobarbituric acid reactive substances (TBARS), interleukin 6 (IL-6), and thromboxane B2 (TXB2) levels. Moreover, a significant prolongation of bleeding time was demonstrated among aspirin, rivaroxaban, and aspirin plus rivaroxaban treated groups. On the other hand, the combination treatment of aspirin plus rivaroxaban showed no marked difference in these biomarkers and bleeding time relative to either drug administered separately. However, a prominent decrease of cardiac 6-keto prostaglandin F1α (6-Keto-PGF1α) level was displayed in the combination treatment when compared with ISO and rivaroxaban-treated groups, whereas no significant improvement was seen in cardiac glycoprotein V (GPV) levels except in aspirin-treated group. The study results demonstrated that rivaroxaban decreases cardiac oxidative stress, inflammation, and platelets reactivity. However, the addition of rivaroxaban to aspirin did not seem to show synergistic antioxidant, anti-inflammatory, or antiplatelet effect.

Impact of atorvastatin on plasma and cardiac biomarkers of inflammation, oxidative stress, and fibrosis in a rat model of streptozotocin-induced diabetes.

Oxidative stress and fibrosis foster the development of cardiovascular disease (CVD) in diabetes. Atorvastatin protects against cardiovascular diseases in diabetes patients. However, the mechanisms are not completely known. This study evaluated the impact of atorvastatin on vascular and myocardial oxidative stress, inflammation, and fibrosis in a model of diabetes. Male Wistar rats were assigned into four groups; control rats, atorvastatin-treated rats (Ator, 40mg/kg given by oral gavage for 6weeks), diabetes rats (DM, single IP 40mg/kg streptozotocin), and diabetes rats treated with atorvastatin (DM + Ator). Serum and cardiac inflammatory, oxidant, and fibrotic markers were measured. Cardiac fibrosis was evaluated by Masson trichrome stain. Streptozotocin-induced diabetes as documented by the marked elevation in blood glucose. Levels of oxidant biomarkers of serum and cardiac nitrite, cardiac nitrate, and cardiac thiobarbituric acid reactive substances (TBARS) were increased in the DM group. The use of atorvastatin reduced nitrite and TBARS levels. Serum and cardiac inflammatory factors of endothelin-1 (ET-1) were elevated in the DM group, and the use of atorvastatin reduced these increases. Cardiac C-reactive protein tended to increase in the DM group and the use of atorvastatin reduced its level. Cardiac interstitial fibrosis was increased in the DM group with a parallel increase in the platelet-derived growth factor level. The use of atorvastatin reduced cardiac fibrosis. Diabetes was associated with an increase in serum and/or myocardial markers of oxidative stress, inflammation, and fibrosis. The use of atorvastatin reduced cardiac interstitial fibrosis and decreased cardiac oxidant and inflammatory biomarkers.

Origanum majorana L. Extract Protects Against Isoproterenol-Induced Cardiotoxicity in Rats.

Coronary artery diseases are the major causes of disabilities and death worldwide. Evidence from the literature has demonstrated that Origanum majorana L. (marjoram) acts as an antioxidant, anti-inflammatory, antiplatelet, and assists in hormonal regulation. However, there is limited scientific evidence describing the signaling pathways associated with the marjoram's positive effect on cardiac injury. Therefore, we aimed to understand the mechanistic protective effects of marjoram on isoproterenol (ISO)-induced myocardial injury in rats. Sprague Dawley rats were randomly assigned into six groups. Marjoram was administrated by oral gavage and isoproterenol was administrated subcutaneously (ISO; 85mg/kg). Heart weight, cardiac enzymes, inflammatory, and oxidative stress biomarkers were measured. The ISO-induced cardiac injury was confirmed by the significant increase in the levels of cardiac enzymes (P value < 0.05), whereas pre-treatment with marjoram normalized these cardiac injury parameters. We also determined that marjoram had a protective effect against ISO-induced increase in C-reactive protein (CRP), IL-6, IL-13, and TNF-α. Additionally, marjoram significantly decreased cardiac thiobarbituric acid reactive substances (TBARS) levels (P value < 0.05) and protected against ISO-induced oxidative stress. We have demonstrated that marjoram decreased both cardiac oxidative stress and inflammation, thus establishing the beneficial effects of marjoram on ISO-induced cardiac injury in rats.

Changes in the cardiac phosphotransfer network associated with oxidative stress in experimentally infected Brucella ovis mice

The aim of this study was to evaluate whether Brucella ovis infection altered the activities of cardiac enzymes belonging to the phosphotransfer network and cause an oxidative imbalance in mice, used as an experimental model. We used hearts from 48 mice in two groups (n = 24 each): uninfected (control group) and infected by B. ovis, collected on days 7, 15, 30, and 60 post-infection (PI). Cardiac cytosolic creatine kinase (CK) activity was higher in infected animals than in the control group on days 30 and 60 PI, while cardiac mitochondrial CK activity was lower at the same moments of infection. Cardiac pyruvate kinase (PK) activity was lower in infected animals than in the control group on day 60 PI, while no significant difference was observed between groups regarding cardiac adenylate kinase (AK) activity. Cardiac thiobarbituric acid reactive substances (TBARS) were higher in infected animals than in the control group on days 30 and 60 PI, while non-protein thiol (NPSH) levels were lower on days 30 and 60 PI. Finally, cardiac SOD activity was higher in infected animals than in the control group on day 60 PI. The inhibition on mitochondrial CK activity caused an impairment of cardiac energy homeostasis, possibly through depletion of ATP production, although cytosolic cardiac CK activity acted in an attempt to restore the mitochondrial ATP levels through a feedback mechanism.

Biochemical effect of cranberry extract on experimentally induced myocardial infarction

Myocardial infarction (MI) is characterized by an inequity of coronary blood supply and demand, which results inmyocardial ischemic injury and damages the cardiomyocytes. Isoproterenol (ISO) is a synthetic catecholamine causetoxicity leading to severe stress in the myocardium of experimental animals. The aim of the present article is to investigatecardioprotective activity of cranberry extract against ISO-induced cardiotoxicity in adult rats. Oral administration ofcranberry extract at a concentration of 75 and 150 mg/kg b.wt. daily for 28 days showed a significant protection againstinducedalteration in plasma total cholesterol (TC), triacyclglycerols (TG), high density lipoprotein (HDL-C), low densitylipoprotein (LDL-C), tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) as well as cardiac superoxide dismutase(SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), catalase (CAT) levels. In addition, cranberry extractreduced plasma Creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) aswell as cardiac thiobarbituric acid reactive substances (TBARS) levels (MDA) as compared to control group. Inconclusion, cranberry extract renders resiliency against isoproterenol cardiotoxicity due to its antioxidant and free radicalscavenging activity

High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension.

Evaluation of in vitro and in vivo antioxidant potential of polysaccharides from Aloe vera (Aloe barbadensis Miller) gel

In the present study, the antioxidant activity of the polysaccharides from aloe vera (Aloe barbadensis Miller) gel was evaluated, in vitro by five established methods, 1,1-diphenyl-2-picrylhydrazyl (DPPH–) radical scavenging, nitric oxide (NO) scavenging, hydrogen peroxide scavenging, superoxide radical (O-2) scavenging and reducing power assay, and in vivo against doxorubicin (DOX)-induced myocardial oxidative stress (OS) in albino wistar rats. The polysaccharides exhibited significant inhibitory activity against DPPH–, superoxide, NO and hydrogen peroxide scavenging assay with significant reducing activity at all concentrations used. DOX-induced (7.5 mg/kg, intravenously) cardiotoxicity manifested biochemically by a significant decrease in blood and tissue glutathione (GSH) along with elevated levels of serum lactate dehydrogenase and creatine phosphokinase. In addition, cardiotoxicity was further confirmed by the significant increase in lipid peroxidation expressed as thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD). Administration of aloe vera polysaccharides for 14 days produced a marked protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum lactate dehydrogenase, serum creatine phosphokinase, cardiac TBARS, CAT and SOD along with increased levels of blood and tissue GSH in a dose-dependent manner. The present investigation is the first to establish the antioxidant potency of the polysaccharides from aloe vera against DOX-induced myocardial OS.

Fenugreek seed extract inhibit fat accumulation and ameliorates dyslipidemia in high fat diet-induced obese rats.

This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28), respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD)) activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.

Effect of soybean oil on atherogenic metabolic risks associated with estrogen deficiency in ovariectomized rats

The aim of the present study was to investigate the cardiac biomarker changes in experimental bilateral ovariectomized (OVX) rats in addition to evaluating the role of soybean oil-supplemented diet to attenuate these alterations. Female rats were divided into four groups and treated for 2 months as follows: groups 1 and 2 fed with standard diet with or without 15% soybean oil. Groups 3 and 4 were bilateral OVX and received the standard diet with or without 15% soybean oil. The results revealed that rats subjected to ovariectomy exhibited an inhibition in estrogen and high-density lipoprotein cholesterol levels and marked increase of lipid profile, low-density lipoprotein cholesterol, and VLDL-C accompanied with a marked elevation in atherogenic index, cardiac enzyme activity, tumor necrosis factor-α, and C-reactive protein. Signs of cardiovascular injury which included an increase in cardiac thiobarbituric acid-reactive substances were concomitantly noticed with a reduction in the reduced glutathione, total antioxidant capacity, and superoxide dismutase. However, supplementation of soybean oil resulted in the restoration of the changed lipid profile and improved cardiac biomarkers near to normal values as well as improved inflammatory and antioxidant status. It was concluded that consumption of soybean oil may have a role in retarding atherosclerosis and risk of cardiovascular disorders associated with estrogen deficiency in ovariectomy status.

Cardiac Contractile Dysfunction and Apoptosis in Streptozotocin-Induced Diabetic Rats Are Ameliorated by Garlic Oil Supplementation

Previous studies have suggested that garlic oil could protect the cardiovascular system. However, the mechanism by which garlic oil protects diabetes-induced cardiomyopathy is unclear. In this study, streptozotocin (STZ)-induced diabetic rats received garlic oil (0, 10, 50, or 100 mg/kg of body weight) by gastric gavage every 2 days for 16 days. Normal rats without diabetes were used as control. Cardiac contractile dysfunction examined by echocardiography and apoptosis evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay were observed in diabetic rat hearts. Additionally, a shift in cardiac myosin heavy chain (MHC) gene expression from α- to β-MHC isoform, decreased levels of superoxide dismutase-1 (SOD-1) and cardiac α-actin, and elevated cardiac thiobarbituric acid reactive substances (TBARS) and caspase- and p38-NFκB-leading apoptosis signaling activities were demonstrated in diabetic hearts. However, these diabetes-related cardiac dysfunctions were almost dose-dependently ameliorated by garlic oil administration. In conclusion, garlic oil possesses significant potential for protecting hearts from diabetes-induced cardiomyopathy.

Enhancement of amlodipine cardioprotection by quercetin in ischaemia/reperfusion injury in rats

AbstractObjectivesTo investigate the possible modification of the cardioprotective effect of amlodipine when co-administered with quercetin in myocardial ischaemia/reperfusion-induced functional, metabolic and cellular alterations in rats.MethodsOral doses of amlodipine (15 mg/kg) and quercetin (5 mg/kg), alone or in combination, were administered once daily for 1 week. Rats were then subjected to myocardial ischaemia/reperfusion (35min/10min). Heart rates and ventricular arrhythmias were recorded during ischaemia/reperfusion progress. At the end of reperfusion, activities of plasma creatine kinase (CK) and cardiac myeloperoxidase were determined. In addition, cardiac contents of lactate, ATP, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total nitrate/nitrite (NOx) were estimated. Finally, histological examination was performed to visualize the protective cellular effects of different pretreatments.Key findingsCombined therapy provided significant improvement in the amlodipine effect toward preserving cardiac electrophysiologic functions, ATP and GSH contents as well as reducing the elevated plasma CK, cardiac TBARS and NOx contents.ConclusionQuercetin could add benefits to the cardioprotective effect of amlodipine against injury induced in the heart by ischaemia/reperfusion.

Enhancement of amlodipine cardioprotection by quercetin in ischaemia/reperfusion injury in rats

To investigate the possible modification of the cardioprotective effect of amlodipine when co-administered with quercetin in myocardial ischaemia/reperfusion-induced functional, metabolic and cellular alterations in rats. Oral doses of amlodipine (15 mg/kg) and quercetin (5 mg/kg), alone or in combination, were administered once daily for 1 week. Rats were then subjected to myocardial ischaemia/reperfusion (35(min)/10(min)). Heart rates and ventricular arrhythmias were recorded during ischaemia/reperfusion progress. At the end of reperfusion, activities of plasma creatine kinase (CK) and cardiac myeloperoxidase were determined. In addition, cardiac contents of lactate, ATP, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and total nitrate/nitrite (NO(x)) were estimated. Finally, histological examination was performed to visualize the protective cellular effects of different pretreatments. Combined therapy provided significant improvement in the amlodipine effect toward preserving cardiac electrophysiologic functions, ATP and GSH contents as well as reducing the elevated plasma CK, cardiac TBARS and NO(x) contents. Quercetin could add benefits to the cardioprotective effect of amlodipine against injury induced in the heart by ischaemia/reperfusion.

Activation of peroxisome proliferator-activated receptor-α by fenofibrate prevents myocardial dysfunction during endotoxemia in rats*

To investigate the effects of fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, on cardiac function in a rat endotoxemia model. Prospective, randomized, controlled study. University research laboratory. Three-month-old male Wistar rats. Animals were fed with standard diet containing no drug or fenofibrate (0.2%) for 14 days. They were then injected intravenously with either 5 mg/kg lipopolysaccharide (LPS and fenofibrate + LPS groups) or saline (control and fenofibrate groups). In the LPS group, body weight loss, metabolic acidosis, and thrombocytopenia confirmed presence of systemic endotoxemia. LPS administration resulted in an early peak in plasma tumor necrosis factor-alpha, decreased cardiac contractility (isolated and perfused heart), reduced myofilament Ca2+ sensitivity (Triton-skinned cardiac fibers), and increased left ventricular nitric oxide (NO) end-oxidation products (NO(x) and NO2), without evidence of myocardial oxidative stress (thiobarbituric acid-reactive substances and antioxidant enzyme activities). Fenofibrate pretreatment (fenofibrate + LPS group) did not alter signs of endotoxemia but prevented reductions in both cardiac contractility and myofilament Ca2+ sensitivity. The peak of plasma tumor necrosis factor-alpha was attenuated, whereas myocardial NO(x) and NO2 remained similar to the LPS group. Oxidative stress was suggested from moderate increase in cardiac thiobarbituric acid-reactive substances and reduced glutathione peroxidase activity. Fenofibrate, an activator of peroxisome proliferator-activated receptor-alpha, may prevent endotoxemia-induced cardiac dysfunction and reduction in myofilament Ca2+ sensitivity. Our data also suggest a mediating role for early peak plasma tumor necrosis factor-alpha, but not for myocardial NO production or oxidative stress.

Endothelin-1–Mediated Increase in Reactive Oxygen Species and NADPH Oxidase Activity in Hearts of Aryl Hydrocarbon Receptor (AhR) Null Mice

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor characterized to play a role in detection and adaptation to environmental stimuli. Genetic deletion of the AhR results in cardiac hypertrophy that is mediated primarily by endothelin-1 (ET-1); ET-1 has been implicated in the elevation of reactive oxygen species (ROS) in the heart, which are thought to contribute to several cardiovascular disorders, including cardiac hypertrophy. Thus, we tested the novel hypothesis that ET-1 induces ROS in AhR null mice via ET(A) receptor activation. We first confirmed the presence of ROS in the hearts of AhR null mice by measuring superoxide (O2*-)-dependent oxidation of dihydroethidium. Ethidium fluorescence was increased 10-fold in the hearts of AhR null mice, compared to the wild type. Then, to elucidate whether ET-1 mediated the increase in ROS, mice were chronically treated with 100 ng/kg/day of the ET(A) receptor antagonist BQ-123. In AhR null mice, BQ-123 significantly reduced elevated plasma 8-isoprostane, a systemic end product of phospholipid oxidation by ROS, and cardiac thiobarbituric acid reactive substances (TBARS), a nonspecific assessment of ROS production. Furthermore, BQ-123 reduced both cardiac lucigenin chemiluminescence and cardiac mRNA expression of NAD(P)H oxidase subunits gp91phox, p47phox, and p67phox in AhR null mice below the levels observed in wild-type mice. These findings demonstrate that ET-1 activation of ET(A) receptors mediates an increase in ROS that is associated with cardiac hypertrophy in AhR null mice. In addition, the ET-1-mediated increase in ROS appears to be initiated via increased NAD(P)H oxidase activity.