Miguel Roehrs

The influence of the hemodialysis treatment time under oxidative stress biomarkers in chronic renal failure patients.

UNLABELLED Oxidative stress possibly helps to promote the progression and complication of chronic renal failure (CRF). Hemodialysis (HD) may aggravate oxidative stress. In addition long time of treatment may intensify the oxidative stress. Thus, the aim of this study was to evaluate the effect of prolonged HD treatment under parameters of the oxidative stress. METHODS Plasmatic thiobarbituric acid reactive substances (TBARS), plasmatic malondialdehyde (MDA), blood delta-aminolevulinate dehydratase (ALA-D) activity, ALA-D reactivation index, and erythrocytic reduced glutathione (GSH) were measured into two different groups of HD patients: recent treatment (n=36; HD duration: 17.7+/-1.71 months), and long time of treatment (n=26; HD duration: 82.2+/-6.32 months), and in a control group (n=40). RESULTS Plasmatic TBARS and MDA levels were both elevated in HD patients. However, only MDA levels had positive correlation with time of HD treatment. Blood ALA-D activity was decreased in HD patients. The ALA-D reactivation index showed increase in HD patients, and it had correlation with the time of HD treatment. Erythrocytic GSH levels were increased in HD patients. CONCLUSIONS Our results indicated that MDA levels and ALA-D reactivation index may be the better biomarkers to evaluate chronic oxidative stress in comparison with others markers analyzed in this study.

N-acetylcysteine on oxidative damage in diabetic rats.

N-acetylcysteine (NAC) is a potent mucolitic agent and also an antioxidant. Its antioxidant action is due to its ability to stimulate reduced glutathione (GSH) synthesis, therefore maintaining intracellular levels. The aim of this study was to evaluate the effects of NAC administered intraperitoneally (i.p.) in a decreasing of oxidative tissue damage in the liver and kidney of alloxan-induced diabetic rats, especially on thiolic groups (nonproteic and proteic groups). Adult male Wistar rats (200–350 g) were used; diabetes was induced accordingly by a single i.p. injection of alloxan monohydrate, and the control group received a similar volume of the vehicle. Lipid peroxidation (LPO) biomarker (malondialdehyde; MDA), δ-ALA-D activity, GSH, superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified to assess the oxidative stress. All tests were performed in tissue homogenates. Creatinine, urea, aspartate transaminase, and alanine transaminase were determined by commercial kits, using serum samples. A significant decrease in LPO (i.e., hepatic and renal) and an increase in δ-aminolevulinate dehydratase activity, especially in the renal tissue, were observed. Also, NAC at 75 mg/kg showed more effective restoration of oxidative stress biomarkers than NAC at 25 mg/kg. Our findings suggest that NAC can be used as an antioxidant agent in diabetes, exhibiting modulatory action on the oxidative stress biomarkers analyzed in this work. Moreover, these findings can contribute to others’ research, regarding the utilization of NAC to ALA-D activity restoration in the kidneys.

Blood thioredoxin reductase activity, oxidative stress and hematological parameters in painters and battery workers: relationship with lead and cadmium levels in blood

Oxidative stress has been shown to be involved in lead and cadmium toxicity. We recently showed that the activity of the antioxidant enzyme thioredoxin reductase (TrxR) is increased in the kidneys of lead‐exposed rats. The present study evaluated the blood cadmium and blood lead levels (BLLs) and their relationship with hematological and oxidative stress parameters, including blood TrxR activity in 50 painters, 23 battery workers and 36 control subjects. Erythrocyte δ‐aminolevulinate dehydratase (δ‐ALA‐D) activity and its reactivation index were measured as biomarkers of lead effects. BLLs increased in painters, but were even higher in the battery workers group. In turn, blood cadmium levels increased only in the painters group, whose levels were higher than the recommended limit. δ‐ALA‐D activity was inhibited only in battery workers, whereas the δ‐ALA‐D reactivation index increased in both exposed groups; both parameters were correlated to BLLs (r = −0.59 and 0.84, P < 0.05), whereas the reactivation index was also correlated to blood cadmium levels (r = 0.27, P < 0.05). The changes in oxidative stress and hematological parameters were distinctively associated with either BLLs or blood cadmium levels, except glutathione‐S‐transferase activity, which was correlated with both lead (r = 0.34) and cadmium (r = 0.47; P < 0.05). However, TrxR activity did not correlate with any of the metals evaluated. In conclusion, blood TrxR activity does not seem to be a good parameter to evaluate oxidative stress in lead‐ and cadmium‐exposed populations. However, lead‐associated changes in biochemical and hematological parameters at low BLLs underlie the necessity of re‐evaluating the recommended health‐based limits in occupational exposure to this metal. Copyright

The relationships between exogenous and endogenous antioxidants with the lipid profile and oxidative damage in hemodialysis patients

BackgroundWe sought to investigate the relationships among the plasma levels of carotenoids, tocopherols, endogenous antioxidants, oxidative damage and lipid profiles and their possible effects on the cardiovascular risk associated with hemodialysis (HD) patients.MethodsThe study groups were divided into HD and healthy subjects. Plasma carotenoid, tocopherol and malondialdehyde (MDA) levels, as well as erythrocyte reduced glutathione (GSH), were measured by HPLC. Blood antioxidant enzymes, kidney function biomarkers and the lipid profiles were analyzed by spectrophotometric methods.ResultsPlasma lycopene levels and blood glutathione peroxidase (GPx) activity were significantly decreased in HD patients compared with healthy subjects. Total cholesterol, low-density lipoprotein cholesterol (LDL-c), creatinine, urea, MDA, GSH, superoxide dismutase (SOD) and catalase (CAT) were significantly increased in HD (p < 0.05). Lycopene levels were correlated with MDA (r = -0.50; p < 0.01), LDL-c (r = -0.38; p = 0.01) levels, the LDL-c/HDL-c index (r = -0.33; p = 0.03) and GPx activity (r = 0.30; p = 0.03). Regression models showed that lycopene levels were correlated with LDL-c (β estimated = -31.59; p = 0.04), while gender was correlated with the TC/HDL-c index and triglycerides. Age did not present a correlation with the parameters evaluated. GPx activity was negatively correlated with MDA levels and with the LDL-c/HDL-c and CT/HDL-c indexes.ConclusionsLycopene may represent an additional factor that contributes to reduced lipid peroxidation and atherogenesis in hemodialysis patients.

The plasma retinol levels as pro-oxidant/oxidant agents in haemodialysis patients

BACKGROUND Oxidative stress is a process involved in haemodialysis-related pathologies such as cerebrovascular diseases. Retinol is the major circulating form of vitamin A and it is elevated in haemodialysis (HD) patients. It is known that these patients present anaemia that is not totally responsive to erythropoietin. The aim of this study was to evaluate the influence of plasma retinol levels on oxidative stress biomarkers, especially on delta-aminolevulinate dehydratase. METHODS Plasma retinol and malondialdehyde (MDA) levels were quantified by HPLC-UV/VIS; blood activities of catalase (CAT), superoxide dismutase (SOD) and delta-aminolevulinate dehydratase (ALA-D) were analysed by spectrophotometric methods, in HD patients (n = 29) and healthy subjects (n = 20). RESULTS The MDA and retinol levels, SOD and CAT activities were significantly increased in HD patients. ALA-D activity was significantly decreased. Retinol levels were correlated with MDA levels (r = 0.68), CAT (r = 0.39), SOD (r = 0.40) and ALA-D (r = -0.55). A partial correlation between retinol levels with ALA-D (r = 0.43), SOD (r = 0.30) and CAT (r = 0.36) activity was found, utilizing MDA levels as co-variable. CONCLUSION Higher retinol levels may be associated with the increase of SOD and CAT activities, but this increase was not sufficient to prevent the lipid peroxidation and ALA-D thiolic group oxidation. In this manner, our results could suggest that high retinol levels contribute as an additional factor to the oxidative tissue damage.

Bixin and Norbixin Have Opposite Effects on Glycemia, Lipidemia, and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

The present study investigated the effects of oral administration of annatto carotenoids (bixin (BIX) and norbixin (NBIX)) on glucose levels, lipid profiles, and oxidative stress parameters in streptozotocin (STZ)-induced diabetic rats. Animals were treated for 30 days in the following groups: nondiabetic control, diabetic vehicle, diabetic 10 mg/kg BIX, diabetic 100 mg/kg BIX, diabetic 10 mg/kg NBIX, diabetic 100 mg/kg NBIX, diabetic metformin, and diabetic insulin. Blood glucose, LDL cholesterol, and triglyceride levels were reduced in the diabetic rats treated with BIX. BIX treatment prevented protein oxidation and nitric oxide production and restored superoxide dismutase activity. NBIX treatment did not change most parameters assessed, and at the highest dose, it increased LDL cholesterol and triglycerides levels and showed prooxidant action (increased protein oxidation and nitric oxide levels). These findings suggested that BIX could have an antihyperglycemic effect, improve lipid profiles, and protect against damage induced by oxidative stress in the diabetic state. Because NBIX is a water-soluble analog of BIX, we propose that lipophilicity is crucial for the protective effect of annatto carotenoids against streptozotocin-induced diabetes.

Astaxanthin prevents changes in the activities of thioredoxin reductase and paraoxonase in hypercholesterolemic rabbits

This study explored the effects of the antioxidant astaxanthin on paraoxonase and thioredoxin reductase activities as well as on other oxidative stress parameters and on the lipid profile in hypercholesterolemic rabbits. Rabbits were fed a standard or a hypercholesterolemic diet alone or supplemented with 50, 100 and 500 mg/100 g of astaxanthin for 60 days. Antioxidant enzymes activities, lipid profile and oxidative stress markers were evaluated in the serum. The hypercholesterolemic diet increased lipids, including unsaturated fatty acids level, whereas it decreased saturated fatty acids level. These changes were accompanied by increased levels of oxidized low-density lipoprotein and oxidized low-density lipoprotein antibodies, as well as lipid and protein oxidation. Astaxanthin (100 and 500 mg/100 g) prevented hypercholesterolemia-induced protein oxidation, whereas 500 mg/100 g of astaxanthin decreased protein oxidation per se. The activities of superoxide dismutase and thioredoxin reductase were enhanced, whereas paraoxonase activity was inhibited in hypercholesterolemic rabbits. All astaxanthin doses prevented changes in thioredoxin reductase and paraoxonase activities. This effect was not related to a direct effect of astaxanthin on these enzymes, because in vitro astaxanthin enhanced thioredoxin reductase and had no effect on paraoxonase activity. Astaxanthin could be helpful in cardiovascular diseases by restoring thioredoxin reductase and paraoxonase activities.

Association Among Microalbuminuria and Oxidative Stress Biomarkers in Patients With Type 2 Diabetes

Aim Hyperglycemia in diabetes mellitus (DM) may be one of the most important factors responsible for the development of oxidative stress, which promotes the main complications in DM patients. Therefore, this study evaluated if the hyperglycemia could be related to oxidative stress biomarkers, lipid profile, and renal function in type 2 diabetes patients without clinic complications. Methods Plasmatic malondialdehyde (MDA), serum protein carbonyl (PCO), serum creatinine levels, microalbuminuria, glycated hemoglobin, and lipid profile were analyzed in 37 type 2 diabetic patients and 25 subjects with no diabetes. Results Serum creatinine levels were within the reference values, but microalbuminuria presented increased levels in all the patients compared with controls (P < 0.05) and above of the reference values. The MDA, PCO, low-density lipoprotein, and triglyceride levels showed positive correlation with microalbuminuria levels. Moreover, glycated hemoglobin presented positive correlation with MDA, PCO, and microalbuminuria levels. Conclusions The hyperglycemia could be responsible for the increase of the microalbuminuria levels and for the oxidation process in lipids and proteins in DM patients. Therefore, we suggested that the microvascular lesion is a direct consequence from hyperglycemia and an indirect one from the increased oxidative stress. Malondialdehyde and protein carbonyl levels could be suggested as additional biochemical evaluation to verify tissue damage in type 2 DM patients.

Butyrylcholinesterase activity is reduced in haemodialysis patients: Is there association with hyperhomocysteinemia and/or oxidative stress?

OBJECTIVES To quantify serum butyrylcholinesterase activity in haemodialysis patients and to evaluate if the homocysteine levels and/or oxidative stress biomarkers have an effect on butyrylcholinesterase. MATERIALS AND METHODS Blood samples were collected from patients and healthy subjects (control). The plasma homocysteine and TBARS levels; serum butyrylcholinesterase activity; blood delta aminolevulinic acid dehydratase (ALA-D) activity and methahaemoglobin were analyzed. The mortality of the patients was also evaluated after 3 years. RESULTS The homocysteine was increased and butyrylcholinesterase decreased compared to control (p<0.05). TBARS and methahaemoglobin were increased and ALA-D decreased (p<0.05). The following correlations were found: homocysteine with butyrylcholinesterase (-0.44); methahaemoglobin (0.41); ALA-D (-0.68); and TBARS (0.66). The partial correlation between homocysteine with butyrylcholinesterase, withdrawn the effect of TBARS, was -0.30; all p<0.05. Moreover, it was observed that 22% of the patients died due to cardiovascular problems. CONCLUSION Thus, our findings support a direct association between the reduction of butyrylcholinesterase by the increase of homocysteine and an indirect effect by increase in oxidative stress.

Evaluation of lipid damage related to pathological and physiological conditions

Several diseases and xenobiotics are known to generate reactive species that may trigger oxidative stress when not properly scavenged by the antioxidant defenses and result in tissue damage. We investigated lipid peroxidation (LPO) as a possible mechanism for tissue damage in some pathologies, in the normal aging process, and in subjects exposed to organic solvents. Plasmatic malondialdehyde (MDA) was quantified by high-performance liquid chromatography with visible wavelength detection in 239 subjects and divided into the following: acute myocardium infarction (AMI), diabetes without complications (D) and hemodialysis (HD) patients; into healthy children, adults, and elderly, all nonexposed to xenobiotics; and into painters occupationally exposed to organic solvents (P). Troponin, glycated hemoglobin, and transminases [aspartate aminotransferase (AST) and alanine aminotransferase] were analyzed. An increase in LPO was observed in AMI, D, HD, and P groups, when compared to healthy adults. No correlation between MDA and age was found. Further, we found positive correlations between MDA versus troponin (r = 0.47), MDA versus HbA1c (r = 0.56), and MDA versus AST (r = 0.41) in AMI, diabetics, and painters, respectively. This work has demonstrated increased lipid and protein damages in myocardium and blood, along with an alteration of hepatic transaminase activities and induction of LPO, suggesting that MDA levels are important to evaluate the extent of tissue alterations and development of acute and chronic conditions.