Isaias Dichi

Decreased oxidative stress in patients with ulcerative colitis supplemented with fish oil ω-3 fatty acids

OBJECTIVE The potential pathogenicity of free radicals may have a pivotal role in ulcerative colitis. Fish oil omega-3 fatty acids exert anti-inflammatory effects on patients with ulcerative colitis (UC), but the precise mechanism of the action of fish oil on oxidative stress is still controversial. The aim of the present work was to verify the blood oxidative stress in patients with UC and determine whether the association of sulfasalazine to fish oil omega-3 fatty acids is more effective than isolated use of sulfasalazine to reduce the oxidative stress. METHODS Nine patients (seven female and two male; mean age = 40 +/- 11 y) with mild or moderate active UC were studied in a randomized crossover design. In addition to their usual medication (2 g/d of sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or placebo for 2-mo treatment periods that were separated by 2 mo, when they only received sulfasalazine. Nine healthy individuals served as control subjects to study the oxidative stress status. Disease activity was assessed by laboratory indicators (C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin, erythrocyte sedimentation rate, albumin, hemoglobin, and platelet count), sigmoidoscopy, and histology scores. Analysis of oxidative stress was assessed by plasma chemiluminescence and erythrocyte lipid peroxidation, both induced by tert butyl hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant status was assayed by total plasma antioxidant capacity (TRAP) and microsomal lipid peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase erythrocyte enzymatic activities were also determined. RESULTS No significant changes were observed in any laboratory indicator or in the sigmoidoscopy or histology scores, with the exception of erythrocyte sedimentation rate, which decreased with both treatments. Oxidative stress was demonstrated by significant decreases in TRAP and LPI levels, increased chemiluminescence induced by t-BuOOH, and higher SOD activity in patients with UC. Treatment with fish oil omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH and LPI to baseline levels but that did not occur when patients received only sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid peroxidation, and catalase were not different from those in the control group. CONCLUSIONS The results indicated that plasma oxidative stress occurs in patients with UC, and there was a significant decrease when the patients used sulfasalazine plus fish oil omega-3 fatty acids. However, there was no improvement in most laboratory indicators, sigmoidoscopy, and histology scores. The results suggested that omega-3 fatty acids may act as free radical scavengers protecting the patients against the overall effect of oxidative stress.

Comparison of ω-3 fatty acids and sulfasalazine in ulcerative colitis

Fish oil omega-3 fatty acids exert antiinflammatory effects on patients with ulcerative colitis. However, a comparative study in patients with mild to moderate ulcerative colitis receiving only sulfasalazine or omega-3 fatty acids has not been performed. We sought to detect changes in the inflammatory disease activity with the use of either fish oil omega-3 fatty acids or sulfasalazine in patients with ulcerative colitis. Ten patients (five male, five female; mean age = 48 +/- 12 y) with mild to moderate active ulcerative colitis were investigated in a randomized cross-over design. They received either sulfasalazine (2 g/d) or omega-3 fatty acids (5.4 g/d) for 2 m.o. Disease activity was assessed by clinical and laboratory indicators, sigmoidoscopy, histology, and whole-body protein turnover (with 15N-glycine). Treatment with omega-3 fatty acids resulted in greater disease activity as detected by a significant increase in platelet count, erythrocyte sedimentation rate, C-reactive protein, and total fecal nitrogen excretion. No major changes in protein synthesis and breakdown were observed during either treatment. In conclusion, treatment with sulfasalazine is superior to treatment with omega-3 fatty acids in patients with mild to moderate active ulcerative colitis.

Influence of uric acid and γ-glutamyltransferase on total antioxidant capacity and oxidative stress in patients with metabolic syndrome

OBJECTIVE Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease related mainly to insulin resistance, but also to oxidative stress. Uric acid and gamma-glutamyltransferase (GGT) levels are also associated with MS and oxidative stress. This study was undertaken to assess the role of GGT and uric acid in adult patients with MS and its relation to oxidative stress and antioxidant defense. METHODS A total of 88 adults (67 with MS and 21 controls) were selected among ambulatory patients and workers of the University Hospital of Londrina, Paraná, Brazil. Oxidative stress was assessed by determination of thiobarbituric acid-reactive substances and tert-butyl hydroperoxide-initiated chemiluminescence and antioxidant defenses by total radical-trapping antioxidant parameter. RESULTS The MS group presented higher significant results (P < 0.0001) than the control group in all parameters of MS and uric acid and GGT levels and significant lower values (P < 0.0001) in high-density lipoprotein cholesterol levels. Thiobarbituric acid-reactive substances and total radical-trapping antioxidant parameter did not show statistically significant differences between groups. However, lipid hydroperoxides, evaluated by tert-butyl hydroperoxide-initiated chemiluminescence, showed higher significant results in the MS group (P = 0.045) than in the control group. Total antioxidant capacity did not decrease and thiobarbituric acid-reactive substances did not increase, probably due to increased uric acid (r = 0.239, P = 0.04) in the MS group. CONCLUSION The present study confirmed that GGT is a strong predictor of MS and that lipid peroxide measured by tert-butyl hydroperoxide-initiated chemiluminescence and GGT activity are reliable markers of oxidative stress in this syndrome.

Evaluation of Oxidative Stress in Overweight Subjects With or Without Metabolic Syndrome

Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross‐sectional study. The control group included 50 healthy individuals with a BMI between 20 and 24.9 kg/m2 and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m2. Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation‐xylenol orange assay compared to overweight subjects without MetS (P < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (P < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.

Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects

OBJECTIVE To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.

Effect of Long-term Fortification of Whey Drink With Ferrous Bisglycinate on Anemia Prevalence in Children and Adolescents From Deprived Areas in Londrina, Paraná, Brazil☆

OBJECTIVE Fortification of food with iron is considered the best sustainable way of preventing iron deficiency when an appropriate diet is not available. The most difficult challenge is to find the ideal combination of iron fortification compound and food vehicle. We investigated the effect of cheese whey drink with 15% of frozen strawberry fortified with ferrous bisglycinate on hemoglobin values in children and adolescents. METHODS The assessed population participates in Public Educational Centers in Londrina, Paraná (southern Brazil), which assist families living in precarious socioeconomic conditions (annual income < 500.00 US dollars per capita). Hemoglobin was measured for 1 y with a Hemocue portable photometer. Anemia was defined as hemoglobin values below 12 g/dL. Thus, hemoglobin was verified in 467 (7 to 14 y) individuals (249 boys and 218 girls). RESULTS Although anemia prevalence did not decrease after 3 mo, there was a statistically significant decrease from 41.9% at the beginning of the study to 26.4% after 6 mo (P < 0.001) and to 9.6% after 1 y (P < 0.001). Statistically significant changes (mean +/- standard deviation) were observed between children and adolescents with hemoglobin values below 11 g/dL (increase of 2.2 +/- 1.03) and above 12 g/dL (increase of 0.35 +/- 1.07; P < 0.0001). CONCLUSION There was a marked reduction in the prevalence of anemia in children and adolescents after long-term fortification of whey drink with ferrous bisglycinate.

Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus

Oxidative stress exerts an important role on the pathophysiological mechanisms of systemic lupus erythematosus (SLE). This study investigated oxidative stress in patients with SLE and its correlation with disease activity, corticosteroid therapy, and liver function biomarkers. The study included 58 patients with SLE and 105 healthy volunteers. Patients showed oxidative stress increase evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), and nitric oxide metabolites. C-reactive protein (CRP) was associated with CL-LOOH and with AOPP. Aspartate aminotransferase correlated significantly with CL-LOOH and with AOPP. Patients with disease activity showed an inverse significant correlation of daily prednisone doses and CL-LOOH and a direct correlation with total antioxidant capacity. In conclusion, patients with SLE have persistent lipoperoxidation and protein oxidation even with inactive disease or mild disease activity. The significant correlation between oxidative stress and CRP suggests that, despite clinical remission, the persistence of an inflammatory condition favors oxidative stress. Oxidative stress was associated with liver enzymes, and this relationship seems to support the hypothesis of drug-induced oxidative stress with consequent liver injury. In relation to non-active disease, patients with active SLE did not present oxidative stress and antioxidant capacity changes, due to the antioxidant drugs used in SLE treatment, especially prednisone.

Comparison of ferrous sulfate and ferrous glycinate chelate for the treatment of iron deficiency anemia in gastrectomized patients

OBJECTIVES Postgastrectomy iron deficiency anemia has a variable prevalence and occurs in 20-50% of patients. Food fortification reports examining ferrous glycinate chelate have shown that it can be 2.5-3.4 times more bioavailable than ferrous sulfate, with minimal gastrointestinal symptoms. The present study was designed as a controlled experimental study including 18 gastrectomized patients with iron deficiency anemia to compare the effects of ferrous sulfate and ferrous glycinate chelate in the treatment of anemia and to evaluate the presence of side effects. METHODS Patients were divided in two groups: group 1 received ferrous sulfate (200 mg twice a day, corresponding to 80 mg of elemental iron) and group 2 received ferrous glycinate chelate (250 mg/d, corresponding to 50 mg of elemental iron) for 4 mo. Laboratory measurements were performed at baseline and after 2 and 4 mo. RESULTS Group 1 showed an apparent recovery in laboratory parameters, with increases in medium corpuscular hemoglobin (P = 0.02), serum iron (P = 0.02), and ferritin (P = 0.04), and a decrease in transferrin (P = 0.002) after 4 mo. Individualized analysis showed that only one patient using ferrous sulfate had anemia at the end of the study in contrast to six patients using ferrous glycinate. In addition, ferritin levels increased above 20 microg/L at the end of the study in seven patients using ferrous sulfate in contrast to one patient using ferrous glycinate. CONCLUSION Patients with iron deficiency anemia after gastrectomy treated with ferrous sulfate had better results in hematologic laboratory parameters than those who used ferrous glycinate chelate.

Disability in patients with multiple sclerosis: influence of insulin resistance, adiposity, and oxidative stress.

OBJECTIVE The aims of the present study were to report the prevalence of insulin resistance (IR) in patients with multiple sclerosis (MS); to verify differences in metabolic and inflammatory biomarkers, and oxidative stress in patients with MS with or without IR; and to assess if IR and adiposity are associated with disability in these patients. METHODS The study enrolled 110 patients with MS and 175 healthy individuals. Patients with MS were divided in those with IR (n = 44) and those without (n = 66). Metabolic and inflammatory markers, oxidative stress, and disability were evaluated by the Extended Disability Status Scale (EDSS). RESULTS IR prevalence was verified in 40% of the patients with MS and in 21.1% of the control group (odds ratio, 2.48; 95% confidence interval, 1.469-4.210; P = 0.0006). Patients with the disease and IR showed higher EDSS (P = 0.031), interleukin (IL)-6 (P = 0.028), IL-17 (P = 0.006), oxidative stress evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (P = 0.029), and advanced oxidation protein products (P = 0.025) than those patients without IR. The multivariate analysis showed that disability was associated with IR evaluated by homeostasis model assessment of insulin resistance (P = 0.030) and adiposity evaluated by waist circumference (P = 0.0179) and body mass index (P = 0.0033). CONCLUSION This is the first study to demonstrate an increase IR prevalence and the association between IR and adiposity with disability assessed by EDSS in patients with MS. IR seems to be associated with chronic inflammatory process and oxidative stress in patients with MS. More studies are warranted to elucidate the mechanisms by which IR and adiposity could contribute to the progression and disability in patients with MS.

Beneficial effects of Lactobacillus plantarum on glycemia and homocysteine levels in postmenopausal women with metabolic syndrome

OBJECTIVE Metabolic syndrome (MetS) in postmenopausal women is an important risk factor for cardiovascular morbidity, especially stroke and coronary heart disease and mortality. Preventing and treating MetS would be useful in preventing disability and promoting normal aging. Previous human studies have found some beneficial effects of Lactobacillus species on some isolated parameters of MetS. Nevertheless, we are not aware, to date, of any study which has verified the influence of probiotics in patients with MetS. Therefore, the aim of the present study was to evaluate the influence of fermented milk with L. plantarum in the classical parameters related to MetS, as well as in other parameters related to cardiovascular risk in postmenopausal women. METHODS Twenty-four individuals were paired by age, ethnicity, and body mass index in two groups: Non-fermented milk (NFM = 12) 80 mL/d and fermented milk (FM = 12) 80 mL/d. Anthropometric and blood pressure measurements, biochemical, inflammatory, and immunologic biomarkers were measured. RESULTS Total cholesterol and γ-glutamyltranspeptidase had a significant reduction both in NFM (P = 0.043 and P = 0.036, respectively) and FM groups (P = 0.010 and P = 0.018, respectively) after 90 d, whereas low-density lipoprotein cholesterol showed a significant reduction in NFM group (P = 0.002) and trend in the FM group (P = 0.092). Glucose and homocysteine levels showed a significant reduction in the FM group compared with the NFM group (P = 0.037 and P = 0.019, respectively). In relation to inflammatory biomarkers, there was a significant decrease in interleukin-6 both in NFM (P = 0.032) and in FM (P = 0.001) groups. CONCLUSION FM with L. plantarum showed more favorable results than NFM in relation to cardiovascular risk factors in postmenopausal women with MetS.