Comparison between the antioxidant status of terrestrial and diving mammals.

Many diving mammals are known for their ability to deal with nitrogen supersaturation and to tolerate apnea for extended periods. They are all characterized by high oxygen-carrying capacity in blood together with high oxygen storage in their muscle mass due to large myoglobin concentrations. The above properties theoretically also imply a high tissue antioxidant defenses (AD) to counteract reactive oxygen species (ROS) generation associated with the rapid transition from apnea to reoxygenation. Different enzymatic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase), and non-enzymatic (levels of glutathione) AD as well as cellular damage (thiobarbituric acid-reactive substances contents, as a measure of lipoperoxidation) were measured in blood samples obtained from anesthetized animals, and also in blood obtained from recently dead diving mammals, and compared to some terrestrial mammals (n=5 in both groups). The results confirmed that diving mammals have, in general, higher antioxidant status compared to non-diving mammals. Apparently, to avoid exposure of tissues to changing high oxygen levels, and therefore to avoid an oxidative stress condition related to antioxidant consumption and increased ROS generation, diving mammals possess constitutive high levels of antioxidants in tissues. These data are in agreement with short-term AD adaptations related to torpor and to animals that experience large daily changes in oxygen consumption. These data are similar to the long-term adaptations of animals that undergo hibernation, estivation, freezing-thawing and dehydration-rehydration processes. In summary, animals that routinely face high changes in oxygen availability and/or consumption seem to show a general strategy to prevent oxidative damage by having either appropriate high constitutive AD and/or the ability to undergo arrested states, where depressed metabolic rates minimize the oxidative challenge.

Content of liver and brain ubiquinol-9 and ubiquinol-10 after chronic ethanol intake in rats subjected to two levels of dietary alpha-tocopherol.

To assess the effect of chronic ethanol ingestion in the content of the reduced forms of coenzymes Q9 (ubiquinol-9) and Q10 (ubiquinol-10) as a factor contributing to oxidative stress in liver and brain, male Wistar rats were fed ad libitum a basal diet containing either 10 or 2.5 mg alpha-tocopherol/100 g diet (controls), or the same basal diet plus a 32% ethanol-25% sucrose solution. After three months treatment, ethanol chronically-treated rats showed identical growth rates to the isocalorically pair-fed controls, irrespectively of alpha-tocopherol dietary level. Lowering dietary alpha-tocopherol led to a decreased content of this vitamin in the liver and brain of control rats, without changes in that of ubiquinol-9, and increased levels of hepatic ubiquinol-10 and total glutathione (tGSH), accompanied by a decrease in brain tGSH. At the two levels of dietary alpha-tocopherol, ethanol treatment significantly decreased the content of hepatic alpha-tocopherol and ubiquinols 9 and 10. This effect was significantly greater at 10 mg alpha-tocopherol/100 g diet than at 2.5, whereas those of tGSH were significantly elevated by 43% and 9%, respectively. Chronic ethanol intake did not alter the content of brain alpha-tocopherol and tGSH, whereas those of ubiquinol-9 were significantly lowered by 20% and 14% in rats subjected to 10 and 2.5 mg alpha-tocopherol/100 g diet, respectively. It is concluded that chronic ethanol intake at two levels of dietary alpha-tocopherol induces a depletion of hepatic alpha-tocopherol and ubiquinols 9 and 10, thus contributing to ethanol-induced oxidative stress in the liver tissue. This effect of ethanol is dependent upon the dietary level of alpha-tocopherol, involves a compensatory enhancement in hepatic tGSH availability, and is not observed in the brain tissue, probably due to its limited capacity for ethanol biotransformation and glutathione synthesis.

Higher levels of antioxidant defenses in enalapril-treated versus non-enalapril-treated hemodialysis patients.

We previously reported chronic treatment with angiotensin-converting enzyme inhibitors (ACEis) increases antioxidant defenses in mice. In the present study, however, we examined various antioxidant defenses in chronic hemodialysis (HD) patients either treated with enalapril (10 mg/d) for at least 6 months (+ACEi; n = 11) or untreated (-ACEi; n = 11). The relationship between antioxidant status and HD was investigated by determining oxidative stress markers and antioxidant defenses in a group of chronic HD patients (n = 33) and a group of age-matched controls (n = 29). The effect of a single HD session on those parameters was also evaluated. Before an HD session (pre-HD), HD patients had significantly lower levels of red blood cell (RBC) glutathione (GSH), selenium-dependent glutathione peroxidase activity (RBC-Se-GPx), plasma ubiquinol-10, and alpha-tocopherol than controls. In a randomly selected group of patients (n = 19), a single HD session caused an additional decrease in RBC-GSH and plasma ubiquinol-10 levels. Plasma thiobarbituric acid reactive substance (TBARS) levels were significantly greater in pre-HD patients than controls. Post-HD plasma TBARS levels were similar to control values. The cohort of +ACEi HD patients had greater pre-HD RBC-GSH content, RBC-Se-GPx activity, and plasma beta-carotene concentrations than -ACEi patients (RBC-GSH: +ACEi, 3.1 +/- 0.9 micromol/mL packed RBCs [PRBCs]; -ACEi, 1.2 +/- 0.3 micromol/mL PRBCs [P < 0.05 v +ACEi]; RBC-Se-GPx: +ACEi, 5.8 +/- 0.7 U/mL PRBCs; -ACEi, 4.3 +/- 0.2 U/mL PRBCs [P < 0.05 v +ACEi]; plasma beta-carotene: +ACEi, 0.54 +/- 0.16 micromol/L plasma; -ACEi, 0.19 +/- 0.05 micromol/L plasma [P < 0.05 v +ACEi]). Results show profound alterations in the circulating antioxidant systems of chronic HD patients and that additional oxidative stress occurs during the HD procedure. In addition, in +ACEi HD patients, the levels of several antioxidant defenses are greater than in those in -ACEi HD patients.

Tissue damage in acute myocardial infarction: selective protection by vitamin E.

A growing amount of scientific evidence supports the participation of oxygen radicals in heart disease and, consequently, a protective effect of vitamin E (VE), beta-carotene (BC), and other antioxidants. The aim of this study was to correlate plasma VE and BC concentration with the clinical course of the acute myocardial infarction (AMI). We evaluated 120 patients that were admitted at the coronary units within 12 h after the development of AMI symptoms. The AMI was diagnosed by clinical and biochemical criteria and by electrocardiography and echocardiography. Plasma VE and BC concentration was determined by high performance liquid chromatography. The patients were separated according to the plasma concentration of VE (group H, VE > 17.5 microM; group L, VE < 17.5 microM). Clinical history of patients, age, sex, associated cardiovascular risk factors, AMI localization, hemodynamic class, and the treatment received were similar between different groups. The blood levels of creatine phosphokinase (CK) evaluated either 24- or 48-h after admittance, were higher in group L than in group H (24 h: H = 436 +/- 31 U/ml vs. L = 642 +/- 84 U/ml; p < .005; 48 h: H = 242 +/- 21 U/ml; L = 423 +/- 82 U/ml, p < 0.005). The number of deflexions in the electrocardiogram at admittance (ECG-D) was significantly higher in group L than in group H (4.7 +/- 0.3 vs. 3.7 +/- 0.2; p < .005). The number of new Q waves in the ECG of release (ECG-Q) was higher in group L than in group H (2.9 +/- 0.3 vs. 2.2 +/- 0.2; p < .05). The number of segments affected in the echocardiograms (EC-S) was: L = 5.3 +/- 0.6 vs. H = 4.4 +/- 0.2; p = 0.11. No significant differences in CK levels, ECG-D, ECG-Q, and EC-S were observed when the patients were separated according their plasma BC levels. These results indicate that a high concentration of plasma VE, but not BC, was associated with a diminution in the creatine phosphokinase release and with the AMI extension.

Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amyotrophic lateral sclerosis patients.

Several parameters indicators of oxidative stress were evaluated in blood from individuals with the sporadic form of amyotrophic lateral sclerosis (SALS) and compared to healthy controls. Plasma levels of 2-thiobarbituric-reactive substances (TBARS), products of lipid peroxidation, were significantly higher (p < 0.03) in the SALS patients compared to controls. The concentration of plasma antioxidants (alpha-tocopherol, beta-carotene, ubiquinol-10 and glutathione) and the activity of red blood cell CuZn superoxide dismutase were not significantly different between the groups. The ratio TBARS/alpha-tocopherol was 47% higher in the SALS individuals than in controls. Protein thiols and protein-associated carbonyls in red blood cell membranes and supernates were similar for both groups. A positive correlation (r2 = 0.91) was found between the concentration of protein-associated carbonyls in red blood cells and the onset of clinical symptoms. These findings are in agreement with several reports showing higher levels of oxidative damage to cell components in ALS.