ß-Cyclodextrins alter the energy metabolism-related enzyme activities in rats.

Although widely used in medicine, separation technology, and other fields, the effects of cyclodextrins on the activities of phosphoryl transfer enzymes have not been previously evaluated. In vivo studies evaluated the function of cyclodextrins as active compounds. Despite the use of cyclodextrins as active compounds, the effects of cyclodextrins on hepatic and renal tissues remain to be fully elucidated. The primary objective of this study was to evaluate the effects of ß- cyclodextrins, methyl-ß-cyclodextrin (M-ß- cyclodextrins), and (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-cyclodextrins) on enzyme activities regulating the maintenance of energy homeostasis in the kidney and liver tissues in relation to toxicity. Serum levels of liver and kidney markers were measured, and oxidative stress parameters were assessed. After 60-day treatments, we observed that the administration of ß-cyclodextrins and M-ß-cyclodextrins inhibited the hepatic activity of pyruvate kinase, an irreversible enzyme within the glycolytic pathway. Additionally, administration of HP-ß-cyclodextrins inhibited creatine kinase activity and increased the total sulfhydryl content in kidneys. Here, we demonstrated for the first time that ß-cyclodextrins, M-ß-cyclodextrins, and HP-ß-cyclodextrins cause bioenergetic dysfunction in renal and hepatic tissues. These findings suggest that understanding the balance between cyclodextrins' efficacy and adverse effects is essential for better accepting their use in medicine.

Occupational risk assessment of exposure to metals in chrome plating workers.

Inhalation of xenobiotics during manufacture process in chrome plating bath produce hazards to workers' health. Chromium (Cr) is a metal widely used by industry, and its hexavalent (VI) form has been classified as mutagenic and carcinogenic. This study aimed to evaluate the occupational risk of exposure to metals in chrome plating workers. Biological monitoring was performed through quantification of Cr, Pb, As, Ni, and V in blood by ICP-MS in 50 male chrome-plating workers from the exposed group and 50 male non-exposed workers. The inflammatory parameters assessed were ß-2 integrin, intercellular adhesion molecule-1 (ICAM-1), and L-selectin expression in lymphocytes. The genotoxicity was evaluated with comet and micronucleus (MN) assays and as a biomarker of oxidative damage the lipid peroxidation (MDA) and protein carbonyl (PCO). The results demonstrated that Cr levels in blood and urine were increased in the exposed group compared to the non-exposed group. Although the biomarkers of exposure proved to be within the levels considered safe in exposed individuals, chrome plating workers presented significantly increase in the percentage of lymphocytes expressing ß-2 integrin, ICAM-1, and L-selectin as well as DNA damage (comet assay) and plasmatic MDA and PCO levels. Therefore, it is possible also assign the injuries caused to lipids, proteins, and DNA assessed due to the increased presence of other metals such as Pb, As, Ni, and V in exposed subjects. These results suggest that exposure to xenobiotics present in the occupational environment in chrome plating industry could play a crucial role toward the inflammation, genetic, and oxidative damage.

Ibuprofen during gestation prevents some changes in physical and reflex development in offspring in a model of hyperleucinemia and maternal inflammation.

Maple Syrup Urine Disease (MSUD) is caused by a severe deficiency in the branched-chain ketoacid dehydrogenase complex activity. Patients MSUD accumulate the branched-chain amino acids leucine (Leu), isoleucine, valine in blood, and other tissues. Leu and/or their branched-chain α-keto acids are linked to neurological damage in MSUD. When immediately diagnosed and treated, patients develop normally. Inflammation in MSUD can elicit a metabolic decompensation crisis. There are few cases of pregnancy in MSUD women, and little is known about the effect of maternal hyperleucinemia on the neurodevelopment of their babies. During pregnancy, some intercurrences like maternal infection or inflammation may affect fetal development and are linked to neurologic diseases. Lipopolysaccharide is widely accepted as a model of maternal inflammation. We analyzed the effects of maternal hyperleucinemia and inflammation and the possible positive impact the use of ibuprofen in Wistar rats on a battery of physics (ear unfolding, hair growing, incisors eruption, eye-opening, and auditive channel opening) and neurological reflexes (palmar grasp, surface righting, negative geotaxis, air-righting, and auditory-startle response) maturation parameters in the offspring. Maternal hyperleucinemia and inflammation delayed some physical parameters and neurological reflexes, indicating that both situations may be harmful to fetuses, and ibuprofen reversed some settings.

Resveratrol and resveratrol-hydroxypropyl-ß-cyclodextrin complex recovered the changes of creatine kinase and Na+, K+-ATPase activities found in the spleen from streptozotocin-induced diabetic rats.

Type 1 diabetes (T1D) is the result of the selective destruction of the pancreatic ß-cells by T cells of the immune system. Although spleen is a secondary lymphoid organ, it is also involved in the T1D pathogenesis. However, the alterations in a variety of cellular processes of this disease need to be further understood. We aimed to analyze the benefits of resveratrol, and its complexed form on diabetic complications in the spleen of rats. To this end, we investigated important enzymes of phosphoryl transfer network, and Na+, K+-ATPase activity. Wistar rats were divided into non-diabetic groups: Control, Ethanol, Resveratrol, Hydroxypropyl-ß-cyclodextrin, Resveratrol-hydroxypropyl-ß-cyclodextrin, and diabetic groups with the same treatments. Diabetes was induced by a single dose of 60 mg/kg of streptozocin intraperitoneally, and treatments by intragastric gavage once daily for 60 days. Hyperglycemia reduced creatine kinase activity, which was reversed by the administration of resveratrol. Na+, K+-ATPase activity was greatly affected, but it was reversed by resveratrol and resveratrol-hydroxypropyl-ß-cyclodextrin. This suggest an energetic imbalance in the spleen of diabetic rats, and in case this also occurs in the diabetic patients, it is possible that resveratrol supplementation could be beneficial to the better functioning of the spleen in diabetic patients.

In vitro and in silico protein corona formation evaluation of curcumin and capsaicin loaded-solid lipid nanoparticles.

Nanotechnology has been an important tool for the production of nanoparticles with controlled release of drugs for therapeutic applications. Here, we produced solid lipid nanoparticles (SLN) loaded with curcumin and capsaicin (NCC) following the overarching goals of green chemistry. Currently, besides evaluating the composition, and size of these, it is necessary to understand the interactions between nanoparticles and the biomolecules present in the biological medium. For this, assays were conducted in order to evaluate the potential formation of the protein 'corona', and to better understand the results obtained in vitro, we also performed an interaction study, in silico, between the NCC components and the main serum protein, albumin. In the first hour of contact between the NCC and the culture medium showed fluctuation in the diameter of the NCC. However, after 24 and 48 h of the incubation period, all NCC concentrations showed an increase in size, which can be attributed to plasma protein adsorption. Since, hard corona takes a few seconds, while the soft corona can be formed in minutes up to a few hours. On the other hand, best docking binding-poses of interaction for the formed docking complexes evaluated suggest interactions following the docking affinity like free energy FEB (Tween 80-bovine serum albumin) ≈ FEB (Span 80-bovine serum albumin) showing a pharmacodynamic pattern based in non-covalent hydrophobic interactions with the bovine serum albumin binding-site. Our in silico results clarify and reinforce our in vitro findings of corona formation, which represents the real interaction with cell membranes in vivo.

Effects of bovine enterovirus and type 1 diabetes on liver and kidney pyruvate kinase activity in an animal model

Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic beta cells. In addition to genetic factors, enteroviruses have been considered the main environmental factor involved in this pathology. Therefore, the objective of this study was to evaluate the effects of streptozotocin-induced diabetes and bovine enterovirus (BEV) on liver and kidney pyruvate kinase activity in rats. Fourteen male Wistar rats were divided in three groups: control, diabetes and a third group, which was fed with water experimentally contaminated by BEV. Increased blood glucose levels were found in both diabetes and enterovirus groups, whereas there were no alterations in the lipid profile. A reduced pyruvate kinase activity was observed in the liver and kidney of animals from diabetes and enterovirus groups. Under our experimental conditions, the ingestion of water experimentally contaminated by BEV induced alterations in glycaemia, and also interfered in the pyruvate kinase activity in liver and kidney of the rats, which might be one of the possible mechanisms involved in the T1D development.

Effects of chronic exposure to hexavalent chromium in water on oxidative stress parameters in Wistar rats

Hexavalent chromium [Cr (VI)] is a metal utilized in different industries and consequently disposed in the environment. It is a toxic substance and its reduction to trivalent Cr [Cr (III)] generates intermediates, which are responsible for the oxidation of molecules, and cause the oxidative stress. Therefore, the aim of this study was to evaluate if Cr (VI) could induce oxidative stress in Wistar rats. In this study, Wistar rats were chronically exposed to 25 and 50 ppm of potassium dichromate in drinking water for 30 days. The levels of Cr were evaluated in the blood and tissues (liver, kidneys, and lungs). Oxidative stress was determined in the liver, kidneys, and lungs and was evaluated by DFCH, TBA-RS and carbonyl test. Antioxidant enzymes were evaluated through catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Regarding the results, Cr concentration was significantly elevated in all tissues, however, it was lower in the lungs. In relation to the oxidative stress parameters, there was a significant increase of DCFH levels in the kidneys and carbonyls in liver and kidneys. Regarding the antioxidant enzymes, SOD was decreased in all organs and GPx was diminished in the kidneys. These data indicated that Cr (VI) could induce oxidative stress in the kidneys and liver due to an imbalance between oxidative and antioxidant parameters. The lungs were little affected, possibly by the lowest chromium accumulation.

Evaluation of hematological, biochemical parameters and thiol enzyme activity in chrome plating workers.

The most commonly used solution in chrome plating bath is chromic acid (hexavalent Cr), and a considerable amount of mists is released into the air and consequently produce hazards to workers. Thus, the aim of this study was to evaluate whether the biomarker of exposure to metals, specially Cr levels, presents associations with hematological and biochemical parameters and if they can alter the activity of enzymes that contain thiol groups such as pyruvate kinase, creatine kinase, adenylate kinase, and δ-aminolevulinate dehydratase. Fifty male chrome plating workers were used for exposed group and 50 male non-exposed workers for control group. For that, biological monitoring was performed through quantification of metals on total blood and urine by inductively coupled plasma mass spectrometry (ICP-MS) and enzyme activity was performed by spectrometry in erythrocytes. In addition, chromium levels in water was quantified and ecotoxicology assay was performed with Allium cepa test. The results demonstrated that blood and urinary chromium levels in exposed group were higher than the control group (p < 0.0001). Furthermore, decreased activity of enzymes was found in those that contain thiol groups from exposed group when compared with the control group (p < 0.001). The water analysis did not present a statistical difference between control and exposed groups (p > 0.05), demonstrating that water did not seem to be the source of contamination. In summary, our findings indicated some toxicology effects observed in the exposed group, such as thiol enzyme inhibition, mainly associated with occupational exposure in chrome plating and besides the presence of other metals, and Cr demonstrated to influence the activity of the enzymes analyzed in this research.

Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney

ABSTRACT Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Thiol/disulfide status regulates the activity of thiol-containing kinases related to energy homeostasis in rat kidney.

Considering that thiol-containing enzymes like kinases are critical for several metabolic pathways and energy homeostasis, we investigated the effects of cystine dimethyl ester and/or cysteamine administration on kinases crucial for energy metabolism in the kidney of Wistar rats. Animals were injected twice a day with 1.6 µmol/g body weight cystine dimethyl ester and/or 0.26 µmol/g body weight cysteamine from the 16th to the 20th postpartum day and euthanized after 12 hours. Pyruvate kinase, adenylate kinase, creatine kinase activities and thiol/disulfide ratio were determined. Cystine dimethyl ester administration reduced thiol/disulfide ratio and inhibited the kinases activities. Cysteamine administration increased the thiol/disulfide ratio and co-administration with cystine dimethyl ester prevented the inhibition of the enzymes. Regression between the thiol/disulfide ratio, and the kinases activities were significant. These results suggest that redox status may regulate energy metabolism in the rat kidney. If thiol-containing enzymes inhibition and oxidative stress occur in patients with cystinosis, it is possible that lysosomal cystine depletion may not be the only beneficial effect of cysteamine administration, but also its antioxidant and thiol-protector effect.

Relationship between depression and diabetes Mellitus / Relação entre depressão e diabetes Mellitus

Objective: To review studies examining the possible relationship between depression and diabetes Mellitus.Methods: Articles were searched in the following databases: the Latin-American and Caribbean Center on Health Sciences, the Scientific Library Online, Base in Nursing and Pubmed. The search was limited to articles published between January 2000 and October 2010. Search terms included: ?diabetes?, ?depression?, ?chronic diseases? and ?psychiatric disorders? Results: A total of 21 articles which examined the relationship between diabetes and depression were included in the present paper. There is a bidirectional relationship between these two chronic diseases. Diabetes could lead to depression due its effects on the quality life of patients, its complications and the difficulty in treatment adhesion. Depression could lead to diabetes on account of alterations in glucose transport function and increased immunoninflamatory activation, which could contribute to insulin resistance and beta islet cell dysfunction. Conclusion: There is a bidirectional relation between diabetes and depression and the nature of this relation is still unclear. However, this research contributes to the comprehension of this relation and possible mechanisms involved, since both diseases should be monitored and deserve attention from health professionals.

Objetivo: Revisar estudos que avaliaram a possível existência da relação entre depressão e diabetes Mellitus.Métodos: Artigos foram pesquisados nas seguintes bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde, Scientific Electronic Library Online, Bases de Dados em Enfermagem e Pubmed. A busca foi limitada aos artigos publicados de janeiro de 2000 a outubro de 2010. Os termos de busca utilizados foram ?diabetes?, ?depressão?, ?doenças crônicas? e ?distúrbios psiquiátricos? Resultados: Um total de 21 artigos que avaliaram a relação entre diabetes e depressão foi incluído e analisado no presente trabalho. Há uma relação bidirecional entre essas duas doenças crônicas. O diabetes poderia levar à depressão por afetar a qualidade de vida dos pacientes, dadas suas complicações e a dificuldade de adesão ao tratamento. A depressão poderia ocasionar o diabetes devido às alterações na função do transporte de glicose e ao aumento da ativação da resposta imunoinflamatória, o que poderia contribuir para a resistência à insulina e para a disfunção da célula betapancreática. Conclusão: Existe uma relação bidiretional entre diabetes e depressão, e a natureza dessa relação permanece desconhecida. Esta revisão contribui para a compreensão dessa relação e dos possíveis mecanismos envolvidos, visto que ambas as doenças devem ser monitoradas e merecem atenção dos profissionais da saúde.

Protective effects of diphenyl diselenide in a mouse model of brain toxicity.

Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)2 (5 µmol/kg), in a mouse model of methylmercury (MeHg)-induced brain toxicity. Our group has previously demonstrated that the oral and repeated administration (21 days) of MeHg (40 mg/L) induced MeHg brain accumulation at toxic concentrations, and a pattern of severe cortical and cerebellar biochemical and behavioral. In order to assess neurotoxicity, the neurochemical parameters, namely, mitochondrial complexes I, II, II-III and IV, glutathione peroxidase (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric acid-reactive substances (TBA-RS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF), as well as, metal deposition were investigated in mouse cerebral cortex. Cortical neurotoxicity induced by brain MeHg deposition was characterized by the reduction of complexes I, II, and IV activities, reduction of GPx and increased GR activities, increased TBA-RS and 8-OHdG content, and reduced BDNF levels. The daily treatment with (PhSe)2 was able to counteract the inhibitory effect of MeHg on mitochondrial activities, the increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the reduction of BDNF content. The observed protective (PhSe)2 effect could be linked to its antioxidant properties and/or its ability to reduce MeHg deposition in brain, which was here histochemically corroborated. Altogether, these data indicate that (PhSe)2 could be consider as a neuroprotectant compound to be tested under neurotoxicity.

Effect of leucine administration to female rats during pregnancy and lactation on oxidative stress and enzymes activities of phosphoryltransfer network in cerebral cortex and hippocampus of the offspring.

Maple Syrup Urine Disease is an inborn error of metabolism caused by severe deficiency in the activity of branched-chain α-keto acid dehydrogenase complex. Neurological disorder is common in patients with maple syrup urine disease. Although leucine is considered the main toxic metabolite, the mechanisms underlying the neuropathology of brain injury are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by leucine administration to female Wistar rats during pregnancy and lactation on some oxidative stress parameters as well as the activities of some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Leucine administration induced oxidative stress and altered the activities of pyruvate kinase, adenylate kinase, mitochondrial and cytosolic creatine kinase. Co-administration of creatine plus pyruvate was partially effective in the prevention of some alterations provoked by leucine administration on the oxidative stress but not in the enzymes of phosphoryltransfer network. These results suggest that non-treated maternal hyperleucinemia may be toxic to the brain of the offspring.

Pyruvate kinase activity and δ-aminolevulinic acid dehydratase activity as biomarkers of toxicity in workers exposed to lead.

Lead (Pb(2+)) is a heavy metal that has long been used by humans for a wide range of technological purposes, which is the main reason for its current widespread distribution. Pb(2+) is thought to enter erythrocytes through anion exchange and to remain in the cell by binding to thiol groups. Pyruvate kinase (PK) is a thiol-containing enzyme that plays a key role in erythrocyte cellular energy homeostasis. δ-aminolevulinic acid dehydratase (δ-ALAD) is the second enzyme in the heme biosynthetic pathway and plays a role in the pathogenesis of Pb poisoning. Our primary objective was to investigate the effect of Pb(2+) on the activity of the thiolenzymes δ-ALAD and PK and on the concentration of glutathione (GSH), a nonenzymatic antioxidant defense, in erythrocytes from Pb-exposed workers. The study sample comprised 22 male Pb workers and 21 normal volunteers (15 men and 6 women). The Pb-exposed workers were employed in manufacturing and recycling of automotive batteries. Basic red-cell parameters were assayed and total white blood cell counts performed. PK and δ-ALAD activity and blood Pb (BPb) concentrations were determined in all subjects. Pb-exposed individuals had significantly greater BPb levels than controls. Both PK and δ-ALAD activity levels were significantly lower in Pb-exposed individuals than in controls. Pb significantly inhibited PK and δ-ALAD activity in a dose-dependent manner. We found that erythrocyte GSH levels were lower in Pb-exposed individuals than normal volunteers. Pb-exposed individuals had lower values than controls for several red cell parameters (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume). These results suggest that Pb inhibits δ-ALAD and PK activity by interacting with their thiol groups. It is therefore possible that Pb disrupts energy homeostasis and may be linked with decreased glucose metabolism because it affects the heme synthesis pathway in erythrocytes, contributing to the cell dysfunction observed in these in Pb-exposed individuals. These results indicate an apparent dose-effect relationship between PK activity and BPb. PK activity in human erythrocytes can be used for biological monitoring of Pb exposure. Study of the mechanisms by which Pb acts may contribute to greater understanding of the symptoms caused by Pb.

Frequency of the anti-glutamic acid decarboxylase immunological marker in patients with diabetes duration longer than three years in southern Brazil.

CONTEXT AND OBJECTIVE: The anti-GAD (glutamic acid decarboxylase) antibody is considered to be an important marker for type 1 diabetes mellitus (DM1), with frequency that varies depending on the population studied and the duration of the disease. Therefore, the aim of this study was to determine the frequency of this autoantibody in a group of patients in southern Brazil with DM1 that had been diagnosed more than three years previously. DESIGN AND SETTING: Analytical cross-sectional study with a control group conducted at the Biomedicine Laboratory of Universidade Feevale. METHODS: This study was conducted between June 2007 and December 2008, and 109 individuals were enrolled during this period. Fifty-eight were DM1 patients and 51 were individuals free from DM1 and without any history of diabetes, who constituted the control group. RESULTS: In the DM1 group, the mean age was 27 ± 1.7 years and 50% were men. The mean fasting blood glucose in the DM1 group was 208 ± 15 mg/dl and mean HbA1c (glycosylated hemoglobin) was 8.7 ± 0.25%. In the control group, the mean fasting blood glucose and HbA1c were 82 mg/dl and 5.0% respectively. Thirty-seven individuals with DM1 (63.8%) were positive for anti-GAD, and this proportion was significantly larger than in the control group. CONCLUSIONS: These results show the high prevalence of anti-GAD in the population of diabetic patients in southern Brazil, thus indicating that the antibody was still present a long time after the disease had been diagnosed.

Frequency of the anti-glutamic acid decarboxylase immunological marker in patients with diabetes duration longer than three years in southern Brazil / Frequência do marcador imunológico de anti-decarboxilase do ácido glutâmico em pacientes com diabetes há mais de três anos no Sul do Brasil

CONTEXT AND OBJECTIVE: The anti-GAD (glutamic acid decarboxylase) antibody is considered to be an important marker for type 1 diabetes mellitus (DM1), with frequency that varies depending on the population studied and the duration of the disease. Therefore, the aim of this study was to determine the frequency of this autoantibody in a group of patients in southern Brazil with DM1 that had been diagnosed more than three years previously. DESIGN AND SETTING: Analytical cross-sectional study with a control group conducted at the Biomedicine Laboratory of Universidade Feevale. METHODS: This study was conducted between June 2007 and December 2008, and 109 individuals were enrolled during this period. Fifty-eight were DM1 patients and 51 were individuals free from DM1 and without any history of diabetes, who constituted the control group. RESULTS: In the DM1 group, the mean age was 27 ± 1.7 years and 50 percent were men. The mean fasting blood glucose in the DM1 group was 208 ± 15 mg/dl and mean HbA1c (glycosylated hemoglobin) was 8.7 ± 0.25 percent. In the control group, the mean fasting blood glucose and HbA1c were 82 mg/dl and 5.0 percent respectively. Thirty-seven individuals with DM1 (63.8 percent) were positive for anti-GAD, and this proportion was significantly larger than in the control group. CONCLUSIONS: These results show the high prevalence of anti-GAD in the population of diabetic patients in southern Brazil, thus indicating that the antibody was still present a long time after the disease had been diagnosed.

CONTEXTO E OBJETIVO: O anticorpo anti-decarboxilase do ácido glutâmico (anti-GAD) é considerado um importante marcador no diabetes mellitus tipo 1 (DM1), cuja frequência varia segundo a população estudada e o tempo de duração da doença. Assim, o objetivo deste estudo foi determinar a frequência deste auto-anticorpo em um grupo de pacientes localizados no Sul do Brasil com mais de três anos de diagnóstico de DM1. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico com grupo controle, realizado no Laboratório de Biomedicina da Universidade Feevale. MÉTODOS: Este estudo foi realizado no período de Junho de 2007 a Dezembro de 2008, em que 109 indivíduos foram incluídos, sendo 58 destes com DM1 e 51 indivíduos sem DM1 e sem antecedentes de diabetes, que constituíram o grupo controle. RESULTADOS: No grupo DM1, a idade média foi 27 ± 1,7 anos e 50 por cento eram homens. A média da glicemia de jejum no grupo DM1 foi 208 ± 15 mg/dL e a HbA1c média foi 8,7 ± 0.25 por cento. No grupo controle a glicemia de jejum média e a HbA1c (hemoglobina glicosilada) foram 82 mg/dL e 5,0 por cento, respectivamente. O anti-GAD foi positivo em 37 (63,8 por cento) indivíduos com DM1, valores significativamente maiores quando comparados com os do grupo controle. CONCLUSÕES: Estes resultados mostram a alta prevalência do anti-GAD na população de pacientes diabéticos da região Sul do Brasil, indicando que o anticorpo está presente após um longo período de diagnóstico da doença.

Ovariectomy alters energy metabolism in rat striatum: effect of supplementation with soy diet rich in isoflavones.

In the present study we investigated the effect of ovariectomy on some parameters of energy metabolism, namely Na(+),K(+)-ATPase and pyruvate kinase activities, as well as the mitochondrial respiratory chain enzymes activities succinate dehydrogenase, complex II and cytochrome c oxidase in rat striatum. The influence of soy diet rich in isoflavones on the effects elicited by ovariectomy on enzyme activities was also evaluated. Female adult Wistar rats were assigned to one of the following groups: sham (submitted to surgery without removal of the ovaries) and ovariectomized. Seven days after surgery animals were fed for 30 days on a special diet with soy protein or a standard diet with casein (control). Rats were sacrificed after treatment and the striatum was dissected. Results showed that rats subjected to ovariectomy presented a significant increase in Na(+),K(+)-ATPase, succinate dehydrogenase and complex II activities. Treatment with isoflavones-rich soy diet was able to reverse the increase of Na(+),K(+)-ATPase activity, but was not effective in reversing the changes caused by ovariectomy on succinate dehydrogenase and complex II activities. Since ovariectomy mimics postmenopausal changes, our findings suggest that dysfunction of brain energy metabolism may be related to neurological symptoms observed in some postmenopausal women.

Effects of inorganic selenium administration in methylmercury-induced neurotoxicity in mouse cerebral cortex.

Selenium can counteract methylmercury (MeHg) neurotoxicity. However, data about the neuroprotective effects of sodium selenite (Na(2)SeO(3)) on the activity of mitochondrial complexes and creatine kinase (mtCK) are scarce. Therefore, this study investigated the effects of the chronic exposure to Na(2)SeO(3) on brain energy metabolism and oxidative stress parameters in MeHg-poisoned mice. Adult male mice were orally treated with MeHg (40 mg L(-1) in drinking water, ad libitum) during 21 days and simultaneously administrated with daily subcutaneous injections of Na(2)SeO(3) (5 µmol kg(-1)), a potential neuroprotectant. Mitochondrial complexes I to IV and mtCK activities were measured in cerebral cortex mitochondria. The cerebro-cortical tissue was also used to evaluate the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) activities, as well as lipid peroxidation. Metal deposition was followed autometalographically (AMG). Na(2)SeO(3) partially prevented MeHg-induced inhibition of complexes II-III, IV and mtCK activities; however, it was unable to prevent MeHg-induced complex I and II inhibition. MeHg increased lipid peroxidation, GR activity and decreased GPx activity in the cerebral cortex; however, Na(2)SeO(3) did not modify such events. Furthermore, Na(2)SeO(3)per se inhibited complexes I, II-III and IV and mtCK activities and increased GPx and GR activities and lipid peroxidation. These data show that inorganic selenium was ineffective in preventing most of the MeHg-induced brain biochemical alterations. However, the most prominent finding was the selenium-induced reduction of cells labelled for metal deposition. Although, the literature supports the beneficial effects of selenium against mercury toxicity, the toxic effects elicited by Na(2)SeO(3), alone or in combination with mercury, should be considered when this compound is proposed as a potential protective therapy for MeHg poisoning.

Chronic variable stress impairs energy metabolism in prefrontal cortex and hippocampus of rats: prevention by chronic antioxidant treatment.

Since chronic stress has been used widely for studying clinical depression and that brain energy metabolism and oxidative stress might be involved in the pathophysiology of this illness, the objective of this study was investigate the activities of pyruvate kinase, complex II and IV (cytocrome c oxidase) in hippocampus and prefrontal cortex of rats submitted to chronic variable stress. We also evaluated if vitamins E and C administration could prevent such effects. During 40 days adult rats from the stressed group were subjected to one stressor per day, at a different time each day, in order to minimize predictability. The stressed group had gained less weight while its immobilization time in the forced swimming test was greater than that of the control group. Results showed that stressed group presented an inhibition in the activities of complex II and cytochrome c oxidase in prefrontal cortex, while in hippocampus just complex IV was inhibited. Pyruvate kinase activity was not altered in stressed group when compared to control. Vitamins E and C administration prevented the alterations on respiratory chain caused by stress. These data suggest that the impairment of energy metabolism and oxidative stress could be related with the pathogenic pathways in stress related disorders.

Lead inhibits in vitro creatine kinase and pyruvate kinase activity in brain cortex of rats.

Lead intoxication is a serious occupational disease that constitutes a major public health problem. Lead, a heavy metal, has been used by humans for many technological purposes, which is the main reason for its widespread distribution. The toxic mechanisms of lead on the molecular machinery of living organisms include metal transport, energy metabolism, diverse enzymatic processes, genetic regulation, and membrane ionic channels and signaling molecules. Since lead is able to cross the blood-brain barrier it may cause neurotoxicity. Creatine kinase and pyruvate kinase are two thiol-containing enzymes that exert a key role for cellular energy homeostasis in brain. Our main objective was to investigate the in vitro effect of lead on pyruvate kinase and creatine kinase activities of extracts and subcellular fractions from the brain cortex of rats in the presence or not of thiol-protecting substances such as glutathione and cysteamine. The results showed that lead inhibited the two enzyme activities and the thiol-protecting substances prevented their inhibition. These results suggest that lead inhibits creatine kinase and pyruvate kinase activity by interaction with their thiol groups. Therefore, lead may disrupt energy homeostasis and this effect may contribute to the neurological dysfunction found in lead exposed individuals.