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).
Graphical abstract
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.
Graphical abstract
Purpose
Hypothyroidism has been shown to induce immunosuppression and both the thyroid status and immunity are affected by zinc deficiency. However, the impact of hypothyroidism on zinc metabolism ...and its possible relationship with the immune status has not yet been deeply explored. Here, our aim was to study whether hypothyroidism may alter zinc metabolism and thus lead to the impairment of T lymphocyte activity.
Methods
Variations in the distribution of zinc in the body were evaluated in PTU-treated hypothyroid mice. The effects of hypothyroidism and zinc deficiency were studied on T lymphocyte proliferation after stimulation both in vitro and in vivo. For in vitro assays, thyroid hormone-free or zinc chelator (TPEN or DTPA)-supplemented media were used. For in vivo assays, lymphocyte activity was evaluated in cells from hypothyroid, T3-treated, and zinc-supplemented mice.
Results
Hypothyroid mice showed lower levels of zinc in femur and lymph nodes than controls. T3 and zinc supplementation reversed these effects. In vitro, both thyroid hormone and zinc deficiency led to a decreased response to mitogen stimulation. However, only zinc deficiency was able to induce lymphocyte apoptosis. Mitogen-stimulated T cells from hypothyroid mice showed impaired proliferation, accompanied by decreased activation of PKC and lower levels of p-ERK, effects that were reversed by T3 replacement or zinc supplementation.
Conclusions
Our results show an important role of zinc deficiency in hypothyroid-mediated T-cell suppression and suggest the importance of evaluating zinc levels and restoring them when necessary to maintain an efficient immune response in hypothyroid patients.
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.
: 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.
: 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.
: 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.
: 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.
Liposomes are today useful tools in different fields of science and technology. A lack of stability due to lipid peroxidation is the main problem in the extension of the use of these formulations. ...Recent investigative works have reported the protective effects of stable nitroxide radicals against oxidative processes in different media and under different stress conditions. Our group has focused its attention on the natural aging of liposomes and the protection provided by the water- and lipid-soluble nitroxide radicals 2,2,6,6-tetramethylpiperdine-1-oxyl (TEMPO) and doxylstearic acids (5-DSA, 12-DSA, and 16-DSA), respectively. Unilamellar liposomes were incubated under air atmosphere at 37°C, both in the absence and in the presence of these radicals. Conjugated dienes, lipid hydroperoxides, TBARS, membrane fluidity, and nitroxide ESR signal intensity were followed as a function of time. Our results demonstrated that doxylstearic acids were more efficient than TEMPO in retarding lipid peroxidation at all the concentrations tested. The inhibition percentages, depending on the total nitroxide concentration, were not proportional to the lipid–water partition coefficient. Furthermore, time-course ESR signals showed a slower decrease for doxylstearic acids than for TEMPO. No significant differences were found among 5-DSA, 12-DSA, and 16-DSA. We concluded that the nitroxide radical efficiency as antioxidant directly depends on both nitroxide concentration and lipophilicity.
Hypothyroidism has been shown to induce immunosuppression and both the thyroid status and immunity are affected by zinc deficiency. However, the impact of hypothyroidism on zinc metabolism and its ...possible relationship with the immune status has not yet been deeply explored. Here, our aim was to study whether hypothyroidism may alter zinc metabolism and thus lead to the impairment of T lymphocyte activity.
Variations in the distribution of zinc in the body were evaluated in PTU-treated hypothyroid mice. The effects of hypothyroidism and zinc deficiency were studied on T lymphocyte proliferation after stimulation both in vitro and in vivo. For in vitro assays, thyroid hormone-free or zinc chelator (TPEN or DTPA)-supplemented media were used. For in vivo assays, lymphocyte activity was evaluated in cells from hypothyroid, T3-treated, and zinc-supplemented mice.
Hypothyroid mice showed lower levels of zinc in femur and lymph nodes than controls. T3 and zinc supplementation reversed these effects. In vitro, both thyroid hormone and zinc deficiency led to a decreased response to mitogen stimulation. However, only zinc deficiency was able to induce lymphocyte apoptosis. Mitogen-stimulated T cells from hypothyroid mice showed impaired proliferation, accompanied by decreased activation of PKC and lower levels of p-ERK, effects that were reversed by T3 replacement or zinc supplementation.
Our results show an important role of zinc deficiency in hypothyroid-mediated T-cell suppression and suggest the importance of evaluating zinc levels and restoring them when necessary to maintain an efficient immune response in hypothyroid patients.
The transition metals iron (Fe) and copper (Cu) are needed at low levels for normal health and at higher levels they become toxic for humans and animals. The acute liver toxicity of Fe and Cu was ...studied in Sprague Dawley male rats (200g) that received ip 0–60mg/kg FeCl2 or 0–30mg/kg CuSO4. Dose and time-responses were determined for spontaneous in situ liver chemiluminescence, phospholipid lipoperoxidation, protein oxidation and lipid soluble antioxidants. The doses linearly defined the tissue content of both metals. Liver chemiluminescence increased 4 times and 2 times after Fe and Cu overloads, with half maximal responses at contents (C50%) of 110μgFe/g and 42μgCu/g liver, and with half maximal time responses (t1/2) of 4h for both metals. Phospholipid peroxidation increased 4 and 1.8 times with C50% of 118μg Fe/g and 45μg Cu/g and with t1/2 of 7h and 8h. Protein oxidation increased 1.6 times for Fe with C50% at 113μg Fe/g and 1.2 times for Cu with 50μg Cu/g and t1/2 of 4h and 5h respectively. The accumulation of Fe and Cu in liver enhanced the rate of free radical reactions and produced oxidative damage. A similar free radical‐mediated process, through the formation HO• and RO• by a Fenton-like homolytic scission of H2O2 and ROOH, seems to operate as the chemical mechanism for the liver toxicity of both metals.
The acute liver toxicity of Fe and Cu overloads, evaluated from dose and time-responses, indicate that a similar chemical mechanism of a free radical‐mediated process seems to operate for the biochemical effects through the formation HO• and RO• by a Fenton-like homolytic scission of H2O2 and ROOH. Display omitted
► Liver oxidative damage is produced by higher than normal Fe and Cu liver contents. ► Metal concentration in liver is linearly related to metal intakes. ► Increased liver Fe and Cu contents similarly produced increased oxidative damage. ► This damage is simultaneous and generated for a common biochemical mechanism. ► Free radical process operate by HO• and RO• generated from H2O2 and ROOH scission.
The rat liver antioxidant response to Fe and Cu overloads (0–60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for ...half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58–66%) and Cu (79–81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110–124μgFe/g and 40–50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60–75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30–92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8–8.5h and Mn-SOD: t1/2: 8.5–8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22–39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.
The antioxidant protection in liver is highly affected after Fe and Cu acute overloads. GSH is the main and fastest-responder antioxidant. An adaptive response of increased expression and activity of SOD1, SOD2 and catalase follows to Fe and Cu overloads. Increased cytosolic levels of Fe2+ and Cu+ and of H2O2 are central to the hypothesis that Fe and Cu toxicities are mediated by increased rates of HO and RO formation. Display omitted
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