Effect of cardiovascular drugs on adenosine deaminase activity.

OBJECTIVE: Adenosine deaminase catalyzes the conversion of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. Because raising adenosine concentration can affect several physiological processes we studied the effect of a selection of cardiological drugs on adenosine deaminase activity in red blood cells and rabbit plasma after 21 days administration. METHODS AND RESULTS: We determined the activity of adenosine deaminase isoenzymes (ADA(1) and ADA(2)). Simvastatin, aspirin, metoprolol, and isosorbide mononitrate significantly decreased plasma total adenosine activity (by 50%, 34%, 29%, and 19%, respectively; P < .05 to P < .001) mainly by decreasing the activity of ADA(2). CONCLUSIONS: As a consequence of decreased ADA(2) activity , the half-life of adenosine will be lengthened. This may, at least in part, explain some of the beneficial effects of analyzed drugs. Our results might be clinically relevant in patients with coronary artery disease, acute coronary syndromes, heart failure, or stroke where the investigated drugs are commonly used. However, our results should be confirmed in large studies in humans.

[The effect of nonsteroidal anti-inflammatory drugs on oxidative/antioxidative balance]. / Wplyw wybranych niesteroidowych leków przeciwzapalnych na równowage oksydacyjno/antyoksydacyjna.

UNLABELLED: Arachidonic acid cascade activated by cyclooxygenase is an important source of reactive oxygen species. Nonsteroidal anti-inflammatory drugs (NSAIDs) can shift an oxidative-antioxidative balance towards antioxidation by inhibiting cyclooxygenase. The aim of the study was to assess the influence of nonsteroidal antiinflammatory drugs on the oxidative-antioxidative balance using animal model. MATERIAL AND METHODS: . In the study acetylsalicylic acid (ASA) as COX-1 and COX-2 inhibitors, and nimesulide as selective COX-2 inhibitor were used. An investigation was carried out on rats (of both sex), divided into two groups of ten animals each. Rats were given intragastrically for three weeks: acetylsalicylic acid (ASA) at doses of 2 and 10 mg/kg bw/day diclofenac at doses of 1 and 5 mg/kg bw/day, and nimesulide at doses of 2.5 mg and 12.5 mg/kg bw/day. Control group received water. Total antioxidant capacity, nitrotyrosine and TBARS in plasma, sulfhydryl groups in whole blood, and thiobarbiturate (TBARS) in hemolysates of erythrocytes concentrations were assessed. RESULTS: The applied doses of diclofenac significantly increased TBARS and nitrotyrosine concentrations and decreased total antioxidant capacity whereas ASA quite the opposite: decreased TBARS and nitrotyrosine concentrations and increased total antioxidant capacity. Nimesulide only at the dose of 12.5 mg/kg bw/day caused a decrease in plasma TBARS and nitrotyrosine concentration. CONCLUSION: This study demonstrated the potential antioxidant properties of ASA and nimesulide but not the other non-selective NSAIDs--diclofenac which turned out to exert pro-oxidative effects. ASA appears to possess stronger antioxidant activity than nimesulide.

[Nonsteroidal antiinflammatory drugs and nitric oxide]. / Niesteroidowe leki przeciwzapalne a tlenek azotu.

UNLABELLED: Despite of belonging to different chemical groups all nonsteroidal antiinflammatory drugs (NSAIDs) exert on antiinflammatory, antypyretic and analgetic effects inhibiting prostaglandin synthesis, preciseley inhibiting first enzyme in arachidonic acid- cyclooxygenase. The aim of the study was to investigate the influence of NSAIDs on nitric oxide synthesis and releasing to bloodstream Acetylsalicic acid (ASA) and diclofenac as COX-1 and COX-2 inhibitors and nimesulide as selective COX-2 inhibitor were used in study. MATERIAL AND METHODS: An experiment was carried out on male Wistar rats administered intragastrically with acetylsalicylic acid in doses: 2.0 and 10.0 mg/kg of body weigh, diclofenac in doses: 1.0 and 5.0 mg/kg body weigh and nimesulide in doses: 2.5 and 12.5 mg/kg body weigh for three weeks. Results compared to control group which received water instead of achive drugs. Nitric oxide was determined by Nitric Oxide Non-Enzymatic Assay of Oxis International. RESULTS: ASA and nimesulide use did not significantly influence NO plasma concentration. Diclofenac administration at the 1.0 and 5.0 mg/kg of body weigh was associated with increased NO concentration by 48.7% and 73.5% respectively. CONCLUSION: NO concentration is not relevant to selective or non selective inhibition of COX by NSAIDs. ASA (a non selective NSAIDs) and nimesulide (sective NSAIDs) do not influence NO concentration, while diclofenac (non selective NSAIDs) causes an increase in NO blood concentration in rats.

[The influence of nonsteroidal anti-inflammatory drugs on deaminase adenosine activity]. / Wplyw niesteroidowych leków przeciwzapalnych na aktywnosc deaminazy adenozyny.

The aim of the study was to evaluate the influence ofnonsteroidal anti-inflammatory drugs on deaminase adenosine activity using animal model. 70 rats of Wistar breed was divided into equal groups of ten. Animals were given intragastrically for three weeks: acetylsalicylic acid (ASA) at doses of 2 and 10 mg/kg bw/day, diclofenac at doses of 1 and 5 mg/kg bw/day, nimesulide at doses of 2.5 mg and 12.5 mg/kg bw/day. Control group received only water. After 21 days rats were decapitated and blood was collected to assess deaminase adenosine activity in plasma and erythrocytes. It was found that all investigated drugs inhibit ADA activity in plasma and ADA2 isoenzyme is responsible for this inhibition. Deaminase adenosine activity in erythrocytes is inhibited by ASA and diclofenac but increased by nimesulide.

[Nitric oxide metabolism]. / Metabolizm tlenku azotu.

Nitric oxide is an important mediator of physiological and pathological processes. It is a lipophilic molecule that contains a single unpaired electron which causes NO to be chemically reactive, and to function as a free radical with a short lifetime. NO can act by direct and indirect effects. Direct effects occur between NO and specific biological molecules whereas indirect effects are mediated by reactive nitrogen oxide species (RNOS) formed from the reaction of NO either with oxygen or superoxide. This review discusses the metabolic pathways of NO.

[The influence of selected nonsteroidal anti-inflammatory drugs on antioxidative enzymes activity]. / Wplyw wybranych niesteroidowych leków przeciwzapalnych na aktywnosc enzymów antyoksydacyjnych.

Three nonsteroidal anti-inflammatory drugs were tested: two inhibitors of COX-1 and COX-2 (acetylosalicylic acid and diclofenac), one inhibitor of COX-2 (nimesulid) and superoxide dismutase, catalase and glutatione peroxidase activity was estimated. The investigations were carried out in rats fed by gastric tube for three weeks with acetylsalicylic acid in doses of 2 and 10 mg/kg body weight, diclofenac in doses 1 and 5 mg/kg body weight and nimesulid in doses 2.5 and 12.5 mg/kg body weight. The results were compared with a control group of rats which obtained water into the stomach. No statistically characteristic changes of superoxide dismutase activity were observed. Catalase activity was statistically decreased after both doses of nimesulid and acetylsalicylic acid at the dose of 10 mg/kg body weight. Both doses of diclofenac increased catalase activity. Glutatione peroxidase activity was statistically decreased after both doses of nimesulid and in the dose 10 mg/kg body weight of acetylsalicylic acid and in the dose 5 mg/kg body weight of diclofenac.

[Nitric oxide and cardiologic drugs]. / Tlenek azotu a leki kardiologiczne.

The influence of simvastatin and metoprolol on nitric oxide synthesis (measured as NO metabolites plasma concentration) was studied. Results. It was revealed that both simvastatin and metoprolol diminish significantly plasma nitric oxide concentration by 24.6% and 23.7% respectively. It was also compared nitric oxide concentrations in plasma of rabbits, after 3 week of mononitrate isosorbitol and molsidomine administration--assuming that applied doses are relevant to maximal doses applied to the human. It was found that molsidomine releases more nitric oxide than mononitrate isosorbitol.

[Nitric oxide--oxidant or antioxidant?]. / Tlenek azotu--oksydant czy antyoksydant?

Nitric oxide (NO), as a free radical, seems to be a potential antioxidant. It takes part in termination of lipid peroxidation reactions. It can be also an oxidant, particularly in indirect reactions with oxygen molecules or superoxide anion.

[Inhibition of adenosine deaminase activity by drugs influencing the cardiovascular system]. / Hamowanie deaminazy adenozyny przez leki wplywajace na uklad sercowo-naczyniowy.

Adenosine deaminase (ADA) is an unique enzyme which catalyzes conversion of adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine respectively. One of physiological roles of this enzyme is modulation of its substrate--adenosine concentration (both intracellular and extraectocellular). In presented work the influence of acetylsalicylic acid, metoprolol, simvastatin, isosorbide mononitrate and molsidomine on total activity of adenosine deaminase and its isoenzymes--ADA1 and ADA2 in vivo was studied. We have affirmed that simvastatin decreased of tADA activity by 50%, acetylsalicylic acid by 34%, metoprolol by 29.1% and isosorbide mononitrate by 19.3%. Only after molsidomine administration were no significant changes in ADA activity observed. The result showed that the decline of ADA activity was mainly due to marked decrease in ADA2 isoenzyme.

Influence of selected cardiological drugs on oxidative status.

The aim of the study was to determine the effect of the often applied drugs in cardiovascular diseases (metoprolol, acetylsalicylic acid, simvastatin and molsidomine) on antioxidative/oxidative balance in vivo. The determination of oxidative status was based on measurements of concentration of: thiobarbituric acid reactive substances (TBARS - lipid peroxidation products), protein carbonyl groups (marker of proteins oxidative injury), nitrotyrosine (marker of NO-mediated tissue damage) and sulfhydryl groups (protein oxidation product). The assays were performed in the plasma and whole blood of rabbits after three weeks of daily intragastric administration of the drugs mentioned above. It was shown that all drugs except acetylsalicylic acid caused an increase in the plasma and hemolysate levels of TBARS. No changes in nitrotyrosine concentration were observed after drug administration. The content of carbonyl groups did not change after administration of metoprolol, but increased significantly after simvastatin and molsidomine administration. Blood sulfhydryl group concentration was not changed by metoprolol but it significantly decreased after acetylsalicylic acid and increased significantly after molsidomine administration.

[Prognostic value of the parameters of left ventricular systolic function in patients with heart failure]. / Wartosc prognostyczna wskazników funkcji skurczowej lewej komory u chorych z niewydolnoscia serca.

UNLABELLED: There are several parameters of left ventricular (LV) systolic function assessment. The calculation of the ejection fraction (EF) strongly relates to the preload and afterload conditions. Wall motion score index (WMSI) seems to be to impractical as the semi-quantitative method. Measurement of the LV pressure rise by Doppler evaluation of mitral regurgitation is a reproducible and an accurate method for dP/dt evaluation. As a method for LV systolic function estimation it does not depend on loading conditions. We have compared the prognostic value of these three methods in patients with a broad spectrum of systolic dysfunction. The study group consisted of 75 patients evaluated by all these methods in years 1995-1999 in our echocardiographic laboratory (73%--men, mean 54 +/- 12 years). In 13 patients the coronary artery disease was diagnosed but LV function was apparently normal, in 35--regional dysfunction after myocardial infarction was described, and in 27--global dysfunction due to idiopathic dilated cardiomyopathy. The EF ranged from 11% to 70% (mean 34 +/- 14%), WMSI--from 1 to 3.6 points (mean 2.2 +/- 0.7), and dP/dt from 235 to 4000 mmHg/s (mean 1108 +/- 698 mmHg/s). The closest relationship was noted between EF and dP/dt (R2=0.50). During 38 +/- 19 months of follow-up, 40 patients died (53%). In the multivariate logistic analysis the only significant parameter related to prognosis was EF (p=0.001). WMSI (p=0.12) and dP/dt (p=0.16) were not statistically significant correlated to death. CONCLUSION: The left ventricular ejection fraction still remains the most important parameter for the evaluation of prognosis in patients with depressed systolic function. Left ventricular pressure rise describes the systolic function but does not have impact on the prognostic evaluation.

[Effect of hyperthyreosis on the concentration of antioxidative vitamins and microelements]. / Wplyw hipertyreozy na zawartosc antyoksydacyjnych witamin i mikroelementów.

In the course of hyperthyreosis reactive oxygen production increases and oxidative stress develops. The consequences of oxidative stress comprise disturbances in balance of pro- and antioxidative agents, including changes in concentration of antioxidative vitamins and microelements. Although the results of published studies concerning changes of concentrations of vitamins and microelements in hyperthyreosis are contradictory, most frequently a decrease of zinc and magnesium concentrations was observed.

[Regional aortic function studied by three-dimensional echocardiography]. / Regionalna funkcja aorty badana metoda echokardiografii trójwymiarowej.

UNLABELLED: Aortic pulsation is caused by the arterial blood pressure variation during the cardiac cycle. Thickening of arterial intima, as well as the presence of atherosclerotic plaques may influence vessel pulsation by increasing wall stiffness. There is no data available concerning regional changes in aortic elasticity in relation with local wall thickness and the magnitude of atherosclerosis. The study group comprised 36 patients (27 men, 9 women, mean age 53 +/- 10 years) referred to our echocardiographic laboratory for transesophageal echocardiography (TEE). TEE probe was placed at the depth of 35 cm. The spatial interval between acquired images was 3 degrees. The reconstructed data sets were reviewed and the border between the aortic wall, plaque and lumen was determined. The reconstruction of a two-centimeter-long segment of aorta was divided by coaxial planes into four longitudinal sections. Thereafter the diastolic and systolic radius of each section, thickness of atherosclerotic plaques and intima-media thickness in each section were measured. The regional beta-index was calculated as Ln (systolic pressure/diastolic pressure)/relative change in regional aortic lumen, where relative change in regional aortic lumen was calculated as the difference between aortic lumen volume in systole and diastole divided by aortic lumen volume in diastole. In total, 144 aortic sections were analyzed. The volume of two-centimeter-long segments of descending aorta ranged from 6.9 cm3 to 31.5 cm3 (mean 12.8 +/- 5.2 cm3) in systole and from 4.9 cm3 to 29.2 cm3 (mean 11.2 +/- 4.9 cm3) in diastole. The volume of the examined sections of the aortic segments ranged from 1.3 cm3 to 10.6 cm3 (mean 3.2 +/- 2.6 cm3) in systole and from 1.1 cm3 to 8.7 cm3 (mean 2.8 +/- 1.5 cm3) in diastole. The pulsation of the aortic sections varied from 0.01 cm3 to 2.7 cm3 (mean 0.4 +/- 0.3 cm3), which constituted 0 to 37% (mean 13 +/- 8%) of the section volume. The thickness of atherosclerotic plaques in the studied aortic sections ranged from 0.0 mm to 1.1 mm (mean 0.3 +/- 0.2 mm) and the intima-media thickness was within the range 1.3 mm to 2.5 mm (mean 1.9 +/- 0.3 mm). The regional beta-index of the individual section ranged from 1.1 to 253.9 (mean 9.3 +/- 24.3). The regional beta-index was statistically significantly dependent on the intima-media thickness (p=0.02). We found no significant correlation between beta-index and the thickness of atherosclerotic plaques in the studied segments (p=0.38). CONCLUSIONS: Transoesophageal three-dimensional echocardiography facilitates quantitative analysis of aortic wall stiffness and regional beta-index measurements. The local variability of beta-index is correlated with intima-media thickness, whereas the correlation with the thickness of atherosclerotic plaques is not statistically significant. These measurements may be of importance in the assessment of the degree of atherosclerosis advancement. It forms new perspectives in diagnostics with the ability to evaluate the influence of pharmacotherapy and life-style modifications.

[The influence of hyperthyroidism on selected parameters of oxidant-antioxidant balance on animal model]. / Wplyw hipertyreozy na wybrane parametry równowagi oksydacyjno-redukcyjnej badane na modelu zwierzecym.

The aim of the experiment was to examine the influence of increased concentration of thyroid hormones on selected parameters of oxidant-antioxidant balance through the analysis of the antioxidant enzymes activity, the content of antioxidant vitamins, and the concentration of the unsaturated fatty acids peroxidation (TBARS). Administration of levothyroxine of the dose 100 micrograms/kg of body mass to rabbits for 21 days caused the increase of TBARS concentration, the decrease of concentration of vitamins C and E, and the increase of SOD activity.

Effect of anthocyanins on selected biochemical parameters in rats exposed to cadmium.

Cadmium is a dangerous occupational and environmental toxin. It accumulates in the human organism mainly in liver and kidneys. Cadmium half-life is about 10 years, so the symptoms of cadmium intoxication may occur several years after the exposure. Until now in treating intoxication with this metal chelating compounds have been used, burdened with numerous undesirable symptoms. In our investigations anthocyanins from Aronia melanocarpa were used to reduce the harmful results caused by cadmium. Administering anthocyanins with cadmium chloride resulted in a statistically significant decrease of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, concentration of bilirubin and urea in blood serum and decreased cadmium cumulation in liver and kidneys in relation to animals receiving cadmium chloride only.

Anthocyanins--an adjunct to cardiovascular therapy?

BACKGROUND: Anthocyanins are one of the most important water-soluble plant pigments. They belong to flavonoids and are derivatives of 2-phenylo-benzo-gamma pyren. They have antioxidant and anti-inflammatory properties and, therefore, may be potentially used to combat oxidative stress, frequently present in cardiovascular diseases. AIM: To assess the effects of anthocyanins from chokeberry (Aronia Melanocarpa) on some parameters of oxidation-reduction balance in an animal model. METHODS: Of 20 male Wistar rats, 10 received for 3 months pure water, and the other rats 10-100 mg/l of anthocyanins from Aronia melanocarpa. Afterwards, blood samples were collected for assessment of the (1) content of substances reacting with thiobarbitural--TBARS, (2) antioxidant status and glutathione peroxidase activity, (3) concentration of sulphydryl groups, and (4) nitrite concentration. RESULTS: Anthocyanins significantly reduced the content of TBARS and thiol protein groups and non-significantly increased glutathione peroxidase activity, total content of antioxidants and nitrite concentration. CONCLUSIONS: Anthocyanins from chokeberry decrease lipid peroxidation which may be potentially used to combat oxidative stress.