Platelet function unaffected by ozonated autohaemotherapy in chronically haemodialysed patients.

BACKGROUND: The therapeutic use of ozone is still a controversial medical strategy due to the potential toxicity of ozone, which is recognized as a highly reactive oxidant. The reactive oxygen species are known to induce platelet aggregation, the process involved in the development of atherosclerosis and cardiovascular events. In the present study, the influence of ozonated autohaemotherapy (O3-AHT) on the platelet function was evaluated in chronically haemodialysed patients with peripheral arterial disease. METHODS: This was an oxygen-controlled, cross-over study, in which nine sessions of autohaemotherapy with oxygen administration as a control were followed by nine sessions of O3-AHT. The platelet function was assessed by the extent of spontaneous aggregation (SPA) and agonist-induced aggregation (AIPA), where different concentrations of adenosine were used as an agonist. RESULTS: There were no differences between SPA and AIPA assessed after nine sessions of O3-AHT and after nine sessions of autohaemotherapy with oxygen administration. SPA and AIPA did not change after the first session of O3-AHT as compared with the levels before this procedure. CONCLUSION: O3-AHT with ozone concentration of 50 microg/ml and citrate as an anticoagulant does not induce platelet aggregation.

The role of adenosine triphosphate citrate lyase in the metabolism of acetyl coenzyme a and function of blood platelets in diabetes mellitus.

Diabetes is known to increase blood platelet activity. Activities of pyruvate dehydrogenase (PDH), adenosine triphosphate (ATP)-citrate lyase (ATPCL), acetyl-coenzyme A (acetyl-CoA) content, malonyl dialdehyde (MDA), synthesis, and platelet aggregation in resting conditions and after activation with thrombin were measured in diabetic subjects and in age- and sex-matched healthy subjects. Activities of ATPCL and PDH, acetyl-CoA content, and thrombin-evoked MDA synthesis as well as platelet aggregation in diabetes were 31%, 51%, 62%, 35%, and 21%, respectively, higher than in healthy subjects. In addition, activation of diabetic platelets caused 2 times greater release of acetyl-CoA from their mitochondria than in controls. Both 1.0 mmol/L (-)hydroxycitrate and 0.1 mmol/L SB-204490 decreased acetyl-CoA content in platelet cytoplasm along with suppression of MDA synthesis and platelet aggregation. These inhibitory effects were about 2 times greater in diabetic than in control platelets. The data presented indicate that the ATPCL pathway is operative in human platelets and may be responsible for provision of about 50% of acetyl units from their mitochondrial to cytoplasmic compartment. Increased acetyl-CoA synthesis in diabetic platelets may be the cause of their excessive activity in the course of the disease. ATPCL may be a target for its specific inhibitors as factors decreasing platelet activity.

Platelet function and acetyl-coenzyme A metabolism in type 1 diabetes mellitus.

Blood platelets take up glucose through insulin-independent GLUT-3 transporter. It is, however, unclear how diabetes affects further steps of glucose and glucose-derived acetyl-coenzyme A (CoA) metabolism in platelets. There is no evidence to explain whether these changes are linked to the disease-induced disturbances in platelet function. We found that activities of some key enzymes of glucose and acetyl-CoA metabolism in platelets were elevated in diabetes. Activities of hexokinase, pyruvate dehydrogenase and ATP-citrate lyase in diabetic platelets were found to be increased by 53, 56 and 88%, respectively. Accordingly, diabetes brought about 86% increase of platelet acetyl-CoA and activation of malonyl dialdehyde synthesis as well as spontaneous and thrombin-induced platelet aggregation by about 56, 50 and 15%, respectively. Significant correlations have been observed between some parameters of acetyl-CoA metabolism, platelet function and serum fructosamine in diabetic patients but not in healthy individuals. Our findings indicate that increased platelet activity in diabetic subjects may, at least in part, result from chronic hyperglycaemia-induced changes in acetyl-CoA metabolism, yielding an increase in its concentration in platelets.