Marker Of Free Radical Generation Research Articles

Urate oxidation during percutaneous transluminal coronary angioplasty and thrombolysis in patients with coronary artery disease

Thrombolysis and percutaneous transluminal coronary angioplasty (PTCA) are kinds of procedures that can be used to restore the blood flow of previously ischemic myocardium that can be the result of excessive production of reactive oxygen and nitrogen species, such as superoxide and hydroxyl radical, hypochlorous acid and peroxynitrite. Reaction of urate with some of these potent oxidants results in allantoin production. In this study, we measured the serum allantoin levels, an oxidation product of urate, and “in vivo” marker of free radical generation in reperfusion of ischemic myocardium. After an overnight fasting state, blood samples were collected from 35 patients with coronary occlusive diseases (7 women and 28 men) and 31 healthy subjects (8 women and 23 men). Serum allantoin and urate levels were measured by a GC-MS method. Serum allantoin levels of patients on PTCA therapy (mean±SD, 27.4 ± 15.2 μmol/l) and thrombolytic therapy (24.6 ± 8.6 μmol/l) were significantly higher than those of the patients without therapy (15.8 ± 6.2 μmol/l, p < 0.05 with PTCA and p < 0.006 with thrombolysis) and healthy controls (12.6 ± 6.3 μmol/l, p < 0.002 with PTCA and p < 0.0001 with thrombolysis). Although serum urate levels in PTCA (380.1 ± 72.6 μmol/l) and thrombolysis (359.5 ± 60.0 μmol/l) were higher than those in the non-therapy patients (336.6 ± 53.8 μmol/l) and controls (318.3 ± 81.0 μmol/l), there were no significant differences among groups ( p > 0.05). The results of the study are consistent with others which have demonstrated, higher urate levels are associated with coronary occlusive diseases. Our data support the hypothesis that generation of ROS occurs during myocardial reperfusion. Increased allantoin levels may be used as an index of increased oxidative stress during reperfusion.

Oxidation of Uric Acid in Rheumatoid Arthritis: Is Allantoin a Marker of Oxidative Stress?

Free radicals are implicated in many diseases including atherosclerosis, cancer and also in rheumatoid arthritis. Reaction of uric acid with free radicals, such as hydroxyl radical and hypochlorous acid (HOCl) results in allantoin production. In this study, we measured the serum allantoin levels, oxidation products of uric acid, as a marker of free radical generation in rheumatoid arthritis. Fasting blood samples were obtained from 21 rheumatoid patients and 15 healthy controls. In this study, the serum allantoin and uric acid levels were measured by a gas chromatography–mass spectrometry method and the ratios were calculated. The mean allantoin and uric acid levels and ratios in the patient group were 22.1±11.3, 280.5±65.0 and 8.0±3.7 μM, while in the control group they were 13.6±6.3, 278.3±53.6 and 4.9±2.1 μM, respectively. The effects of gender, age, menopausal status, duration of disease and medications on serum allantoin and uric acid levels of the patient and control groups were studied. Our results suggest that uric acid acts as a free radical scavenger and thus is converted to allantoin. Increased allantoin levels suggest the possible involvement of free radicals in rheumatoid arthritis.

Lipid peroxides, nitric oxide and essential fatty acids in patients with Plasmodium falciparum malaria

Long chain polyunsaturated fatty acids derived from essential fatty acids have been shown to be toxic to Plasmodium falciparum both in vitro and in vivo. Here, we present evidence to suggest that in patients with Plasmodium falciparum malaria the levels of lipid peroxides (a marker of free radical generation) nitric oxide (a potent free radical with immunomodulatory actions), and concentrations of linoleic acid (LA) and alpha-linolenic acid (ALA) are low, whereas those of eicosapentaenoic acid (EPA) are high. The ability of the fatty acids to kill P. falciparum is dependent on their capacity to stimulate free radical generation in neutrophils and macrophages. EPA is more potent than LA in killing the parasite. In view of this, the results of the present study suggest that in patients with P. falciparum malaria the decreased levels of lipid peroxides and nitric oxide may contribute to the persistence of the infection, whereas elevated levels of EPA may be a feeble attempt to overcome this defect.

Captopril Lowers Coronary Venous Free Radical Concentration After Direct Current Cardiac Shocks

Direct current (DC) shocks to the heart cause morphologic and functional myocardial damage. Previous studies have suggested that acute DC shock injury is free radical mediated and that the administration of antioxidant enzymes superoxide dismutase and catalase can reduce the level of DC shock-induced free radicals. Angiotensin-converting enzyme (ACE) inhibitors are clinically used drugs that may scavenge free radicals or reduce free radical generation. The objective of our study was to determine whether the ACE inhibitor captopril lowers free radicals after DC shocks. In six open-chest dogs, we administered 100-J DC shocks to the epicardium, before and after administration of captopril, 3 mg/kg. We used electron paramagnetic resonance measurements of arterial and coronary venous ascorbate free radical (AFR) as a real-time marker of free radical generation (total oxidative flux). Captopril resulted in a significant lowering of coronary venous AFR concentration: the peak rise in AFR after 100-J shocks was 17.3+/-3.4% (mean +/- SEM before captopril vs. 3.2+/-4.0% after captopril; p<0.05). Captopril lowers coronary venous AFR concentration after high-energy epicardial shocks.

Oxidation Products of Uric Acid and Ascorbic Acid in Preterm Infants with Chronic Lung Disease

Allantoin, the oxidation product of uric acid (UA), can be used as an in vivo marker of free radical generation. The aims of the present study were to evaluate the allantoin changes in plasma and bronchoalveolar lavage fluid (BALF) as well as to examine plasma levels of ascorbic acid (AA) and its oxidation product, dehydroascorbic acid (DHAA), in infants with or without chronic lung disease (CLD) during the first week of life. The study population was 20 infants of 24–30 weeks gestation, comprising 10 who subsequently developed CLD and 10 without CLD. In the CLD infants, the plasma allantoin/UA ratio showed a significant increase after day 1 and continued to increase gradually to reach a peak on day 6 (6.5 ± 4.1% for CLD and 2.1 ± 0.9% for non-CLD infants). The allantoin/UA ratio in BALF was also higher in CLD infants and the difference reached significance on days 4–6 (41.2 ± 15.8% for CLD and 11.7 ± 9.9% for non-CLD infants). In contrast to allantoin, the plasma DHAA/AA ratio did not differ between the 2 groups throughout the study period. Our findings that the allantoin/UA ratios were significantly higher in CLD than non-CLD infants not only in plasma but also in BALF, and that the intergroup differences of this ratio in both plasma and BALF was more prominent in the latter half of the first week of life further confirm our previous speculation that oxygen radicals are involved in the development of neonatal CLD.

New evidence for the involvement of oxygen radicals in triggering neonatal chronic lung disease.

We measured the plasma concentration of allantoin, an oxidation product of uric acid and an "in vivo" marker of free radical generation, within 24-48 h after birth in 10 premature infants who subsequently developed chronic lung disease (CLD) and 9 infants without CLD (non-CLD). The plasma allantoin level (mean +/- SD, 25.9 +/- 9.8 microM for CLD versus 11.0 +/- 5.7 microM for non-CLD, p < 0.01) and the allantoin/urate ratio (5.8 +/- 2.0% for CLD infants versus 2.4 +/- 0.9% for non-CLD infants, p < 0.01) were significantly higher in the CLD group than those in the non-CLD group. These observations suggest the possible involvement of oxygen radicals in triggering CLD. In addition, the plasma allantoin concentration and the allantoin/urate ratio may be useful early predictors of the development of CLD.

Ascorbyl free radical as a real-time marker of free radical generation in briefly ischemic and reperfused hearts. An electron paramagnetic resonance study.

The role of free radicals in myocardial reperfusion injury remains controversial. We have developed a new method using ascorbyl free radical (AFR) as a real-time, quantitative marker of free radical generation during myocardial reperfusion. A total of 35 dogs were studied. Twelve open-chest dogs underwent either 5 minutes (n = 5) or 20 minutes (n = 7) of coronary artery occlusion and 30 minutes of reperfusion. Seven additional animals undergoing 20 minutes of coronary occlusion also received the antioxidant enzymes superoxide dismutase and catalase, beginning 10 minutes before occlusion through the end of reperfusion. Exogenous ascorbate was infused intravenously, and the concentration of AFR in the great cardiac vein was continuously measured by electron paramagnetic resonance spectroscopy. Preocclusion AFR concentration was similar in the three groups. Upon reperfusion, AFR rose significantly in each animal group (P < .05). However, the AFR rise in the 20-minute-occlusion group, 38 +/- 17%, was significantly greater than in the 5-minute-occlusion group, 27 +/- 14% (P < .002). In addition, in the animals that received superoxide dismutase and catalase, the rise in the AFR was markedly attenuated, 13 +/- 6% (P < .002). Two dogs that received ascorbate but did not undergo coronary artery occlusion/reperfusion sequences showed no change in coronary venous AFR signal, indicating the stability of the signal over time. Five dogs received ascorbate while undergoing interventions to alter coronary venous flow: intravenous saline, dobutamine, dipyridamole, and nitroglycerin. Coronary venous AFR changes were minimal despite large coronary flow alterations, indicating that the AFR signal is independent of changes in coronary venous flow.(ABSTRACT TRUNCATED AT 250 WORDS)