Biochemical regulatory processes in the control of oxidants and antioxidants production in the brain of rats with iron and copper chronic overloads.

Iron [Fe(II)] and copper [Cu(II)] overloads in rat brain are associated with oxidative stress and damage. The purpose of this research is to study whether brain antioxidant enzymes are involved in the control of intracellular redox homeostasis in the brain of rats male Sprague-Dawley rats (80-90 g) that received drinking water supplemented with either 1.0 g/L of ferrous chloride (n = 24) or 0.5 g/L cupric sulfate (n = 24) for 42 days. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione transferase (GT) activities in brain were determined by spectrophotometric methods and NO production by the content of nitrite concentration in the organ. Chronic treatment with Fe(II) and Cu(II) led to a significant decrease of nitrite content and SOD activity in brain. Activity of NADPH oxidase increased with Cu(II) treatment. Concerning Fe(II), catalase and GT activities increased in brain after 28 and 4 days of treatment, respectively. In the case of Cu(II), catalase activity decreased whereas GT activity increased after 2 and 14 days, respectively. The regulation of redox homeostasis in brain involves changes of the activity of these enzymes to control the steady state of oxidant species related to redox signaling pathways upon Cu and Fe overload. NO may serve to detoxify cells from superoxide anion and hydrogen peroxide with the concomitant formation of peroxynitrite. However, the latest is a powerful oxidant which leads to oxidative modifications of biomolecules. These results suggest a common pathway to oxidative stress and damage in brain for Cu(II) and Fe(II).

Nitric oxide, chronic iron and copper overloads and regulation of redox homeostasis in rat liver.

Iron [Fe(II)] and copper [Cu(II)] ions produced liver oxidative stress and damage, and as a consequence, changes in the antioxidant protection. The objective of this work is to evaluate whether control of redox homeostasis in chronic overload of Fe(II) and Cu(II) is associated with nitric oxide (NO) and antioxidant enzymes protection in liver. Male Sprague-Dawley rats of 80-90 g received the standard diet ad libitum and drinking water supplemented with either 1.0 g/L of ferrous chloride (0.1% w/v, n = 24) or 0.5 g/L cupric sulfate (0.05% w/v, n = 24) for 42 days. The activities of the enzymes involved in the control of cellular redox homeostasis, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), were determined by spectrophotometric methods, and NO production was determined by the determination of nitrite levels in liver. Chronic overload with Fe(II) and Cu(II) led to a significant increase of NO production while hampering the activity of NADPH oxidase. Meanwhile, the animals supplemented with Fe(II) showed a decrease in SOD and Gpx activities in liver homogenates with respect to baseline activity after 7 days of treatment, whereas the rats which received Cu(II) showed an increased SOD and catalase activity after 28 and 7 days of chronic overload. Further research is required to understand whether the modulation of the activity of these enzymes upon Cu and Fe overload is involved in a common toxic pathway or may serve to control the steady state of oxidant species related to redox signaling pathways.

Brain antioxidant responses to acute iron and copper intoxications in rats.

Dose- and time-dependent antioxidant responses to Fe (0-60 mg kg(-1)) and Cu overloads (0-30 mg kg(-1)) in rat brains are described by the C50 and the t1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50-80%) with a t1/2 of 9-10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C50 for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32-36 µg Fe g(-1) brain and 10-18 µg Cu g(-1) brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46-68% with a t1/2 of 10-11 h and lipophilic antioxidants decreased by 75-45% with a t1/2 of 10-12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100-90% after Fe and Cu loads), with a t1/2 of 8-12 h. GPx-4 activity decreased after both metal loads by 73-27% with a t1/2 of 8-4 h with decreased protein expression.

Oxidative damage to rat brain in iron and copper overloads.

This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 µg of Fe per g and from 3.6 to 34 µg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 µg of Fe per g of brain and 15 µg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 µg of Fe per g and 20 µg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 µg of Fe per g and 18% for Cu with a C50 of 10 µg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

Iron, zinc, and copper nutritional status in children infected with Helicobacter pylori.

OBJECTIVE: : Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. PATIENTS AND METHODS: : A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. RESULTS: : Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio = 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio = 1.35 [95% CI 0.67-2.70]). Crude beta coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 microg/dL (95% CI 2.12-17.37 microg/dL) in copper concentrations. CONCLUSIONS: : This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.

Factors associated with H. pylori epidemiology in symptomatic children in Buenos Aires, Argentina.

AIM: To determine prevalence of H pylori infection in symptomatic children in Buenos Aires, Argentina, and to investigate factors associated with H pylori positivity. METHODS: A total of 395 children with upper gastrointestinal symptoms referred to the Gastroenterology Unit of the Children Hospital "Sor Maria Ludovica" were evaluated for the presence of H pylori by the (13)C-Urea Breath Test ((13)C-UBT). A questionnaire was applied to the recruited population. RESULTS: Prevalence of H pylori infection was 40.0% in this population (mean age 9.97 +/- 3.1 years). The factors associated with H pylori positivity were number of siblings (P < 0.001), presence of pet cats (P = 0.03) and birds (P = 0.04) in the household, and antecedents of gastritis among family members (P = 0.01). After multivariate analysis, number of siblings [Odds ratio (OR) = 1.39; 95% CI, 1.20-1.61] and contact with pet cats (OR = 1.76; 95% CI, 1.00-3.09) remained as variables associated with H pylori infection. CONCLUSION: The prevalence of H pylori infection in children with upper gastrointestinal symptoms in Argentina was similar to that reported in developed countries. Children from families with a higher crowding index and presence of pet cats have a higher risk of being colonized with H pylori.

Effect of a probiotic food as an adjuvant to triple therapy for eradication of Helicobacter pylori infection in children.

OBJECTIVE: Current recommendations for treatment of Helicobacter pylori infection include a proton pump inhibitor in combination with two antibiotics. We evaluated the potential activity of a probiotic food as an adjuvant to antibiotic triple therapy for eradication of H. pylori infection in children from Buenos Aires, Argentina. METHODS: Sixty-five children who tested positive for H. pylori, as diagnosed by (13)C-urea breath test and endoscopy, were included in this study. Patients were randomized to receive 1-wk triple therapy plus probiotic food (treated group) or milk placebo (control) that was administered for 3 mo. Probiotic food consisted of 250 mL of a commercial yogurt containing Bifidobacterium animalis and Lactobacillus casei (10(7) colony-forming units/mL). Post-treatment urea breath test controls were performed 1 and 3 mo after the end of triple therapy. RESULTS: We found no significant differences in H. pylori eradication rates (ERs) at 1 and 3 mo between the treated group (ER = 45.5% and 42.4%) and the control group (ER = 37.5% and 40.6%). Relative risks between groups were 0.87 (95% confidence interval 0.58-1.32, P = 0.345) in the first month and 0.97 (95% confidence interval 0.64-1.46, P = 0.542) in the third month. CONCLUSIONS: We could not demonstrate an adjuvant effect of the studied probiotic food to triple therapy in the eradication of H. pylori infection in children in Buenos Aires, Argentina. However, we found lower ERs than those reported for the same therapeutic scheme in developed countries, indicating that bacterial resistance and alternative therapeutic strategies should be studied.