Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Nanotoxicology ; 15(2): 257-275, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33503388

RESUMO

Safety on the use of magnetic nanomaterials (MNMs) has become an active topic of research given all the recent applications of these materials in various fields. It is known that the toxicity of MNMs depends on size, shape, and surface functionalization. In this study, we evaluate the biocompatibility with different aquatic organisms of engineered MNMs-CIT with excellent aqueous dispersion and long-term colloidal stability. Primary producers (the alga Pseudokirchneriella subcapitata), primary consumers (the rotifer Lecane papuana), and predators (the fish, Danio rerio) interacted with these materials in acute and sub-chronic toxicity tests. Our results indicate that P. subcaptita was the most sensitive taxon to MNMs-CIT. Inhibition of their population growth (IC50 = 22.84 mg L-1) elicited cell malformations and increased the content of photosynthetic pigments, likely due to inhibition of cell division (as demonstrated in AFM analysis). For L. papuana, the acute exposure to MNMs shows no significant mortality. However, adverse effects such as decreased rate of population and altered swimming patterns arise after chronic interaction with MNMs. For D. rerio organisms on early life stages, their exposure to MNMs results in delayed hatching of eggs, diminished survival of larvae, altered energy resources allocation (measured as the content of total carbohydrates, lipids, and protein), and increased glucose demand. As to our knowledge, this is the first study that includes three different trophic levels to assess the effect of MNMs in aquatic organisms; furthermore, we demonstrated that these MNMs pose hazards on aquatic food webs at low concentrations (few mgL-1).


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Cloretos/toxicidade , Compostos Férricos/toxicidade , Compostos Ferrosos/toxicidade , Nanoestruturas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/análise , Cloretos/química , Compostos Férricos/química , Compostos Ferrosos/química , Cadeia Alimentar , Larva/efeitos dos fármacos , Fenômenos Magnéticos , Microalgas/efeitos dos fármacos , Nanoestruturas/química , Tamanho da Partícula , Rotíferos/efeitos dos fármacos , Propriedades de Superfície , Poluentes Químicos da Água/química , Peixe-Zebra/crescimento & desenvolvimento
2.
Neurotox Res ; 34(3): 640-648, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29949107

RESUMO

Molecules exhibiting antioxidant, neuroprotective, and regulatory properties inherent to natural products consumed by humans are gaining attention in biomedical research. Ferulic acid (FA) is a phenolic compound possessing antioxidant and cytoprotective properties. It is found in several vegetables, including sugarcane, where it serves as the main antioxidant component. Here, we compared the antioxidant and cytoprotective effects of FA with those of the total sugarcane aqueous extract (SCAE). Specifically, we assessed biochemical markers of cell dysfunction in rat cortical brain slices and markers of physiological stress in Caenorhabditis elegans upon exposure to toxins evoking different mechanisms of neurotoxicity, including direct oxidative stress and/or excitotoxicity. In rat cortical slices, FA (250 and 500 µM), but not SCAE (~ 270 µM of total polyphenols), prevented the loss of reductive capacity induced by the excitotoxin quinolinic acid (QUIN, 100 µM), the pro-oxidant agent ferrous sulfate (FeSO4, 25 µM), and the dopaminergic pro-oxidant 6-hydroxydopamine (6-OHDA, 100 µM). In wild-type (N2) C. elegans, FA (38 mM) exerted protective effects on decreased survival induced by FeSO4 (15 mM) and 6-OHDA (25 mM), and the motor alterations induced by QUIN (100 mM), FeSO4, and 6-OHDA. In contrast, SCAE (~ 13.5 mM of total polyphenols) evoked protective effects on the decreased survival induced by the three toxic agents, the motor alterations induced by FeSO4, and the reproductive deficit induced by FeSO4. In addition, FA was unable to reverse the decreased survival induced by all these toxins in the skn-1-/- strain (VC1772), which lacks the homolog of mammalian Nrf2, a master antioxidant gene. Altogether, our results suggest that (1) both FA and SCAE afford protection against toxic conditions, (2) not all the effects inherent to SCAE are due to FA, and (3) FA requires the skn-1 pathway to exert its protective effects in C. elegans.


Assuntos
Ácidos Cumáricos/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Saccharum/química , Análise de Variância , Animais , Animais Geneticamente Modificados , Coeficiente de Natalidade , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Compostos Ferrosos/toxicidade , Técnicas In Vitro , Ferro/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Oxidopamina/toxicidade , Extratos Vegetais/química , Ácido Quinolínico/toxicidade , Ratos , Ratos Wistar
3.
Drug Des Devel Ther ; 9: 2585-97, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26005335

RESUMO

BACKGROUND AND AIMS: Iron deficiency is common in inflammatory bowel disease, yet oral iron therapy may worsen the disease symptoms and increase systemic and local oxidative stress. The aim of this study was to compare the effects of oral ferrous sulfate and iron polymaltose complex on inflammatory and oxidative stress markers in colitic rats. METHODS: Animals were divided into four groups with ten animals each. Rats of three groups received dextran sodium sulfate to induce colitis and animals of two of these groups received 5 mg iron/kg of body weight a day, as ferrous sulfate or iron polymaltose complex, for 7 days. Gross colon anatomy, histology of colon and liver, stainings of L-ferritin, Prussian blue, hepcidin, tumor necrosis factor-α, and interleukin-6, as well serum levels of liver enzymes, inflammatory markers, and iron markers, were assessed. RESULTS: Body weight, gross anatomy, crypt injury and inflammation scores, inflammatory parameters in liver and colon, as well as serum and liver hepcidin levels were not significantly different between colitic animals without iron treatment and colitic animals treated with iron polymaltose complex. In contrast, ferrous sulfate treatment caused significant worsening of these parameters. As opposed to ferrous sulfate, iron polymaltose complex caused less or no additional oxidative stress in the colon and liver compared to colitic animals without iron treatment. CONCLUSION: Iron polymaltose complex had negligible effects on colonic tissue erosion, local or systemic oxidative stress, and local or systemic inflammation, even at high therapeutic doses, and may thus represent a valuable oral treatment of iron deficiency in inflammatory bowel disease.


Assuntos
Colite/induzido quimicamente , Compostos Férricos/toxicidade , Compostos Ferrosos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Colite/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Feminino , Compostos Férricos/administração & dosagem , Compostos Ferrosos/administração & dosagem , Hematínicos/administração & dosagem , Hematínicos/toxicidade , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Ratos , Ratos Sprague-Dawley
4.
BMC Complement Altern Med ; 13: 262, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-24119308

RESUMO

BACKGROUND: Reactive oxygen species (ROS) are important mediators in a number of degenerative diseases. Oxidative stress refers to the imbalance between the production of ROS and the ability to scavenge these species through endogenous antioxidant systems. Since antioxidants can inhibit oxidative processes, it becomes relevant to describe natural compounds with antioxidant properties which may be designed as therapies to decrease oxidative damage and stimulate endogenous cytoprotective systems. The present study tested the protective effect of two xanthones isolated from the heartwood of Calophyllum brasilienses against FeSO4-induced toxicity. METHODS: Through combinatory chemistry assays, we evaluated the superoxide (O2·â»), hydroxyl radical (OH·), hydrogen peroxide (H2O2) and peroxynitrite (ONO⁻) scavenging capacity of jacareubin (xanthone III) and 2-(3,3-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone (xanthone V). The effect of these xanthones on murine DNA and bovine serum albumin degradation induced by an OH· generator system was also evaluated. Additionally, we investigated the effect of these xanthones on ROS production, lipid peroxidation and glutathione reductase (GR) activity in FeSO4-exposed brain, liver and lung rat homogenates. RESULTS: Xanthone V exhibited a better scavenging capacity for O2·â», ONOO⁻ and OH· than xanthone III, although both xanthones were unable to trap H2O2. Additionally, xanthones III and V prevented the albumin and DNA degradation induced by the OH· generator system. Lipid peroxidation and ROS production evoked by FeSO4 were decreased by both xanthones in all tissues tested. Xanthones III and V also prevented the GR activity depletion induced by pro-oxidant activity only in the brain. CONCLUSIONS: Altogether, the collected evidence suggests that xanthones can play a role as potential agents to attenuate the oxidative damage produced by different pro-oxidants.


Assuntos
Antioxidantes/farmacologia , Calophyllum/química , Compostos Ferrosos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Xantonas/farmacologia , Animais , Química Encefálica/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Glutationa Redutase/metabolismo , Rim/química , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
5.
Exp Eye Res ; 113: 172-81, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23791636

RESUMO

Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Fosfolipases A2 do Grupo V/fisiologia , Degeneração Macular/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Retina/efeitos dos fármacos , Acetilação , Acetiltransferases/metabolismo , Animais , Western Blotting , Bovinos , Citosol/metabolismo , Eletroforese em Gel de Poliacrilamida , Inibidores Enzimáticos/farmacologia , Compostos Ferrosos/toxicidade , Fosfolipases A2 do Grupo V/antagonistas & inibidores , Sobrecarga de Ferro/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositóis/metabolismo , Fosfatidilserinas/metabolismo , Fosfolipases A/metabolismo , Fosfolipases A/fisiologia , Retina/metabolismo
6.
Neurochem Int ; 61(5): 749-58, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22732705

RESUMO

Both elevated iron concentrations and the resulting oxidative stress condition are common signs in retinas of patients with age-related macular degeneration (AMD). The role of phospholipase A(2) (PLA(2)) during iron-induced retinal toxicity was investigated. To this end, isolated retinas were exposed to increasing Fe(2+) concentrations (25, 200 or 800 µM) or to the vehicle, and lipid peroxidation levels, mitochondrial function, and the activities of cytosolic PLA(2) (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)) were studied. Incubation with Fe(2+) led to a time- and concentration-dependent increase in retinal lipid peroxidation levels whereas retinal cell viability was only affected after 60 min of oxidative injury. A differential release of arachidonic acid (AA) and palmitic acid (PAL) catalyzed by cPLA(2) and iPLA(2) activities, respectively, was also observed in microsomal and cytosolic fractions obtained from retinas incubated with iron. AA release diminished as the association of cyclooxygenase-2 increased in microsomes from retinas exposed to iron. Retinal lipid peroxidation and cell viability were also analyzed in the presence of cPLA(2) inhibitor, arachidonoyl trifluoromethyl ketone (ATK), and in the presence of iPLA(2) inhibitor, bromoenol lactone (BEL). ATK decreased lipid peroxidation levels and also ERK1/2 activation without affecting cell viability. BEL showed the opposite effect on lipid peroxidation. Our results demonstrate that iPLA(2) and cPLA(2) are differentially regulated and that they selectively participate in retinal signaling in an experimental model resembling AMD.


Assuntos
Compostos Ferrosos/toxicidade , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Fosfolipases A2/metabolismo , Retina/enzimologia , Animais , Bovinos , Isoenzimas/metabolismo , Isoenzimas/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Técnicas de Cultura de Órgãos , Fosfolipases A2/fisiologia
7.
Drug Chem Toxicol ; 35(1): 48-56, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21919597

RESUMO

Here, we compare the influence of molecular structural modifications of diphenyl diselenide (DPDS) and diphenyl ditelluride (DPDT) with their naphthalene analogs, 1-dinapthyl diselenide (1-NapSe)2, 2-dinapthyl diselenide (2-NapSe)2, 1-dinapthyl distelluride (1-NapTe)2, and 2-dinapthyl ditelluride (2-NapTe)2. Fe(II)-induced hepatic thiobarbituric acid reactive species (TBARS) was in the order [(2-NapTe)2] > [(2-NapSe)2] > [(DPDS)] > [(1-NapSe)2] > [(1-NapTe)2]> [(DPDT)]. For sodium nitroprusside (SNP)-induced hepatic TBARS, the order was [(2-NapTe)2] > [(DPDT)] > [(1-NapSe)2] > [(2-NapSe)2] > [(1-NapTe)2] > [(DPDS)]. For Fe(II) and SNP-induced renal TBARS, the orders were [(2-NapTe)2] > [(1-NapTe)2] = [(DPDT)] > [(1-NapSe)2] > [(2-NapSe)2] > [(DPDS)] and [(2-NapTe)2] > [(1-NapTe)2] > [(1-NapSe)2] > [(2-NapSe)2] > [(DPDS)] > [(DPDS)], respectively. The present investigation shows that DPDS was less potent and the change in the organic moiety from an aryl to napthyl group dramatically changed the potency of diselenides. These results suggest that minor changes in the organic moiety of aromatic diselenides can profoundly modify their antioxidant properties. In view of the fact that the pharmacological properties of organochalcogens are linked, at least in part, to their antioxidant properties, it becomes important to explore the pharmacological properties of dinaphtyl diselenides and ditellurides.


Assuntos
Antioxidantes/farmacologia , Derivados de Benzeno/farmacologia , Compostos Organometálicos/farmacologia , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/química , Derivados de Benzeno/química , Compostos Ferrosos/toxicidade , Nitroprussiato/toxicidade , Compostos Organometálicos/química , Compostos Organosselênicos/química , Relação Estrutura-Atividade
8.
Neurochem Int ; 53(6-8): 199-206, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18692105

RESUMO

The purpose of the present study was to investigate the involvement of phosphatidylcholine (PC) signalling in synaptic endings incubated under oxidative stress conditions. Synaptosomes purified from adult rats (4 months old) cerebral cortex were exposed to oxidative insult (FeSO(4), 50microM) or vehicle, and diacylglycerol (DAG) generation and free fatty acid (FFA) release were subsequently evaluated using exogenous [(14)C]PC as substrate. DAG formation increased after 5, 30, and 60min of Fe(2+)-exposure with respect to the control conditions. The contribution of PC-specific phospholipase C (PC-PLC) and phospholipase D (PLD) pathways to DAG generation was evaluated using ethanol in the enzyme assays. Phosphatidylethanol (PEth) production was measured as a marker of PLD activity. In the presence of ethanol (2%) iron significantly stimulated DAG and PEth production at all times assayed. FFA release from PC, however, was inhibited after 5 and 60min of iron exposure. Similar results were observed in aged animals (28 months old) when compared with adult animals. DAG generation from PC was also evaluated in the presence of the tyrosine kinase inhibitors genistein and herbimycin A. Inhibition of tyrosine kinase activity did not modify the stimulatory effect exerted by iron on PC-PLC and PLD activities. Moreover, the presence of LY294002 (a specific PI3K inhibitor) did not alter DAG production. Our results demonstrate that oxidative stress induced by free iron stimulates the generation of the lipid messenger DAG from PC in synaptic endings in adult and aged rats.


Assuntos
Córtex Cerebral/metabolismo , Ferro/toxicidade , Estresse Oxidativo/fisiologia , Fosfatidilcolinas/metabolismo , Terminações Pré-Sinápticas/metabolismo , Transdução de Sinais/fisiologia , Envelhecimento/metabolismo , Animais , Córtex Cerebral/fisiopatologia , Diglicerídeos/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Compostos Ferrosos/toxicidade , Glicerofosfolipídeos/metabolismo , Ferro/metabolismo , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Terminações Pré-Sinápticas/efeitos dos fármacos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/toxicidade , Transdução de Sinais/efeitos dos fármacos , Sinaptossomos , Fosfolipases Tipo C/metabolismo
9.
Pharmacology ; 82(2): 127-37, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18607114

RESUMO

UNLABELLED: Iron deficiency is a common worldwide problem leading to several morbidities including anemia. Although oral iron is the first choice in iron deficiency therapy, it may produce gastrointestinal (GI) and liver disorders. The aim of our study was to evaluate: (1) acute toxicity (LD(50)) in different oral iron compounds such as ferrous sulfate (FS), iron amino chelate (AC) and iron polymaltose complex (IPC) and (2) possible differences in early and late toxicity in the GI tract and liver between them. METHODS: Hematological variables, liver enzymes, oxidative stress markers (thiobarbituric-acid-reactive substances, reduced glutathione, catalase, glutathione peroxidase, CuZn superoxide dysmutase) in intestinal mucosa and liver homogenates, and morphological parameters (gross anatomy, histology) were evaluated in non-anemic rats. RESULTS: LD(50) was lower (p < 0.01) in FS versus iron AC and IPC. The liver enzymes were increased in the FS group (p < 0.05). The FS group presented gastric mucosal erosions and the iron AC group showed submucosal hemorrhages in the lower GI tract (colon and rectum) versus the IPC and control groups. In the small intestine, the villi/crypt ratio and goblet cells per villus were significantly (p < 0.01) reduced in the FS and iron AC groups versus IPC. The eosinophils per villus were increased (p < 0.01) in the FS and iron AC groups versus the IPC and control groups. Ferritin was elevated (p < 0.01) in the IPC group versus FS and iron AC in the small intestine and liver. The oxidative stress markers were all significantly (p < 0.01) altered in the FS and iron AC groups versus the IPC and control groups in the intestinal mucosa and liver. CONCLUSION: FS exhibited important acute toxicity as well as early and late GI tract and liver toxicity. Despite showing similar LD(50) as IPC, iron AC presented differences regarding early and late GI tract and liver toxicity versus IPC.


Assuntos
Compostos Férricos/toxicidade , Compostos Ferrosos/toxicidade , Quelantes de Ferro/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas , Feminino , Compostos Férricos/administração & dosagem , Ferritinas/efeitos dos fármacos , Ferritinas/metabolismo , Compostos Ferrosos/administração & dosagem , Gastroenteropatias/induzido quimicamente , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Quelantes de Ferro/administração & dosagem , Dose Letal Mediana , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Testes de Toxicidade Aguda
10.
Food Chem Toxicol ; 44(3): 425-35, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16263202

RESUMO

World consumption of natural juices is increasing as a consequence of the human search for a healthier life. The juice production industry, especially for orange juice, is expanding in several countries and particularly in Brazil. Despite scientific data reporting beneficial properties derived from juice consumption, some components of juices have been identified as mutagenic or carcinogenic. Carcinogenic or genotoxic effects may be mediated by the interaction of juice components with transition metals or by sub-products of juice auto-oxidation. In this study, the mutagenic potential of orange juice and two metallic agents used in dietary supplementation, FeSO(4) and CuSO(4), were investigated using the comet assay in mouse blood cells (in vivo). Both metal compounds were genotoxic for eukaryotic cells after 24h treatment at the doses used. Significant damage repair was observed after 48h of treatment with the same compounds. Orange juice had a modulating effect on the action of metallic sulfates. In the case of iron treatment, the presence of the orange juice had a preventive, but not restorative, effect. On the other hand, in the case of copper treatment, the effects were both preventive and restorative. PIXE (particle induced X-ray emission) analysis indicated a positive correlation between DNA damage and the hepatic levels of iron and a negative correlation between whole blood copper and DNA damage. A negative correlation between hepatic iron and whole blood copper content was also seen in the treatment with both ferrous and cupric sulfates.


Assuntos
Bebidas/análise , Citrus sinensis , Sulfato de Cobre/toxicidade , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Compostos Ferrosos/toxicidade , Análise de Variância , Animais , Bebidas/toxicidade , Ensaio Cometa , Qualidade de Produtos para o Consumidor , Relação Dose-Resposta a Droga , Feminino , Cinética , Fígado/química , Masculino , Camundongos , Oxirredução , Substâncias Protetoras
11.
Pharmacol Res ; 51(5): 427-35, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15749457

RESUMO

The extract of Mangifera indica L. (Vimang) is able to prevent iron mediated mitochondrial damage by means of oxidation of reduced transition metals required for the production of superoxide and hydroxyl radicals and direct free radical scavenging activity. In this study we report for the first time the iron-complexing ability of Vimang as a primary mechanism for protection of rat liver mitochondria against Fe2+ -citrate-induced lipoperoxidation. Thiobarbituric acid reactive substances (TBARS) and antimycin A-insensitive oxygen consumption were used as quantitative measures of lipoperoxidation. Vimang at 10 microM mangiferin concentration equivalent induced near-full protection against 50 microM Fe2+ -citrate-induced mitochondrial swelling and loss of mitochondrial transmembrane potential (DeltaPsi). The IC50 value for Vimang protection against Fe2+ -citrate-induced mitochondrial TBARS formation (7.89+/-1.19 microM) was around 10 times lower than that for tert-butylhydroperoxide mitochondrial induction of TBARS formation. The extract also inhibited the iron citrate induction of mitochondrial antimycin A-insensitive oxygen consumption, stimulated oxygen consumption due to Fe2+ autoxidation and prevented Fe3+ ascorbate reduction. The extracted polyphenolic compound, mainly mangiferin, could form a complex with Fe2+, accelerating Fe2+ oxidation and the formation of more stable Fe3+ -polyphenol complexes, unable to participate in Fenton-type reactions and lipoperoxidation propagation phase. The strong DPPH radical scavenging activity with an apparent IC50 of 2.45+/-0.08 microM suggests that besides its iron-complexing capacity, Vimang could also protect mitochondria from Fe2+ -citrate lipoperoxidation through direct free radical scavenging ability, mainly lipoperoxyl and alcoxyl radicals, acting as both a chain-breaking and iron-complexing antioxidant. These results are of pharmacological relevance since Vimang could be a potential candidate for antioxidant therapy in diseases related to abnormal intracellular iron distribution or iron overload.


Assuntos
Antioxidantes/farmacologia , Compostos Ferrosos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Mangifera , Mitocôndrias Hepáticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Ácido Ascórbico/farmacologia , Ácido Cítrico , Compostos Ferrosos/metabolismo , Técnicas In Vitro , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/ultraestrutura , Dilatação Mitocondrial/efeitos dos fármacos , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Ratos
12.
Biol Trace Elem Res ; 94(1): 73-8, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12907829

RESUMO

The iron bioavailability and acute oral toxicity in rats of a ferrous gluconate compound stabilized with glycine (SFG), designed for food fortification, was studied in this work by means of the prophylactic method and the Wilcoxon method, respectively. For the former studies, SFG was homogeneously added to a basal diet of low iron content, reaching a final iron concentration of 20.1 +/- 2.4 mg Fe/kg diet. A reference standard diet using ferrous sulfate as an iron-fortifying source (19.0 +/- 2.1 mg Fe/kg diet) and a control diet without iron additions (9.3 +/- 1.4 mg Fe/kg diet) were prepared in the laboratory in a similar way. These diets were administered to three different groups of weaning rats during 23 d as the only type of solid nourishment. The iron bioavailability of SFG was calculated as the relationship between the mass of iron incorporated into hemoglobin during the treatment and the total iron intake per animal. This parameter resulted in 36.6 +/- 6.2% for SFG, whereas a value of 35.4 +/- 8.0% was obtained for ferrous sulfate. The acute toxicological studies were performed in two groups of 70 female and 70 male Sprague-Dawley rats that were administered increasing doses of iron from SFG. The LD50 values of 1775 and 1831 mg SFG/kg body wt were obtained for female and male rats, respectively, evidencing that SFG can be considered as a safe compound from a toxicological point of view.


Assuntos
Compostos Ferrosos/metabolismo , Compostos Ferrosos/toxicidade , Alimentos Fortificados/toxicidade , Ferro/metabolismo , Animais , Disponibilidade Biológica , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
13.
Arch Latinoam Nutr ; 51(1 Suppl 1): 26-34, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11688078

RESUMO

Iron is estimated to be deficient in the diets of one fifth of the world's population. Iron is commonly provided as a supplemental nutrient in industrialized countries for uses of choice. In other countries of the world, it may be required as an overt addition to the diet to prevent iron deficiency. This may be accomplished through fortification of a common food. As a micronutrient, iron has a relatively narrow range of safety--whether given as a supplement or fortificant, it must be in a high enough dose to be appreciably absorbed, but low enough to avoid toxicity. This concern can be ameliorated by careful choice of the form of iron administered. A source of iron which has proven to be highly bioavailable, yet regulated by dietary need, is iron chelated with amino acids. The structural integrity and longevity of these compounds have been proven by valid chemical and instrumental tests. Proofs of safety of iron amino acid chelate in the dietary administration of iron to swine in both multigenerational and longevity studies are reported. Formal tests of toxicity utilizing ferrous bisglycinate chelate (Ferrochel) carried out in accordance to US-FDA guidelines are also summarized. Ferrochel has been demonstrated to have a No Observable Adverse Effect Level (NOAEL) of at least 500 mg per kg rat body weight, the highest dose tested. This and other results of the detailed toxicity test, as well as other tests of safety and efficacy, have resulted in the US-FDA acknowledging that this product is Generally Recognized As Safe (GRAS) under its approved conditions of use as a source of iron for food enrichment and fortification purposes.


Assuntos
Compostos Ferrosos/toxicidade , Glicina/análogos & derivados , Glicina/toxicidade , Quelantes de Ferro/toxicidade , Animais , Disponibilidade Biológica , Feminino , Compostos Ferrosos/química , Compostos Ferrosos/metabolismo , Alimentos Fortificados , Glicina/química , Glicina/metabolismo , Humanos , Quelantes de Ferro/química , Quelantes de Ferro/metabolismo , Dose Letal Mediana , Masculino , Ratos , Suínos
14.
Behav Brain Res ; 124(1): 77-85, 2001 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-11423168

RESUMO

Two experiments investigated the effects of Fe(2+), administered postnatally to rat pups on days 10-12, upon tests of memory performance and motor behaviour. In experiment I, Wistar rat pups were administered Fe(2+) at doses of either 2.5, 7.5, 15.0 or 30.0 mg/kg, or vehicle, postnatally, and tested in the open-field at 3 months of age, followed 6 weeks later by testing in the radial arm maze. In the open-field test, only the 30.0 mg/kg Fe(2+) group showed a significantly decreased number of ambulations, but not rearings. In the radial arm maze, all four dose groups, demonstrated deficits in acquisition performance from test days 3 to 5. Retention quotients confirmed the cognitive deficits over all four Fe(2+) groups. In experiment II, rats were administered either 2.5, 7.5 or 22.5 mg Fe(2+) per kg, or vehicle, postnatally, and tested in the inhibitory avoidance (IA) conditioning and retention test at 3 months of age. In the IA conditioning test, groups were either given five 10-min preexposures to the test chamber (preexposed) or simply moved to another cage (non-preexposed). IA retention was blocked in non-preexposed rats administered 7.5 and 22.5 mg Fe(2+) per kg whereas in preexposed rats the 7.5 mg/kg group did not differ from the control (vehicle) group, although the preexposed control group showed significantly better retention than the non-preexposed control group. Postnatal iron administration appears to induce long-lasting detrimental effects upon performance of both appetitively and negatively reinforced tests of memory. Analysis of iron content indicated significant increases in the substantia nigra of the 7.5, 15.0 and 30.0 mg/kg dose groups, but not in the 2.5 mg/kg dose group. Postnatal iron administration appears to induce far-reaching effects upon the performance of certain learned behaviours.


Assuntos
Encéfalo/efeitos dos fármacos , Compostos Ferrosos/toxicidade , Rememoração Mental/efeitos dos fármacos , Administração Oral , Fatores Etários , Animais , Animais Recém-Nascidos , Relação Dose-Resposta a Droga , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos
15.
Biol Trace Elem Res ; 62(1-2): 65-73, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9630425

RESUMO

The iron compounds used for food fortification have to meet certain requisites related to their bioavailability, absorption mechanism, and toxicity, since they will be consumed by a massive population group. With these purposes, we evaluated a new product used for the iron fortification of milk and lacteous derivatives, called SFE-171, which is a ferrous sulfate, microencapsulated with phospholipids. The bioavailability studies were carried out using four groups of 30 female mice each. In two groups, we studied the absorption of ferrous ascorbate and ferrous sulfate, both in water as reference standards, which show absorptions of 13.1+/-4.9% and 13.2+/-4.3%, respectively. With the third group, we studied the absorption of ferrous sulfate in milk; its value, 7.9+/-3.2%, is significantly lower than that of the remaining groups, with a p < 0.01. The studies with SFE-171 in milk, were performed on the fourth group, with a result of 11.6+/-4.5%, demonstrating that its absorption does not differ significantly from that of the reference standards. The absorption mechanism was determined by means of in vivo self-displacement studies of the ferrous ion and the SFE-171, taking ferrous sulfate as the reference compound. For this study, 210 female mice were used, and no significant difference between the absorption mechanism of both products could be observed. Toxicity studies of the new product with regard to ferrous sulfate were carried out with two groups of 70 female mice each and two groups of 70 male mice each. The lethal dose 50% LD50 for SFE-171 and for ferrous sulfate was 1200 and 680 mg/kg for female mice and 1230 and 670 mg/kg for male mice, respectively, demonstrating that the toxicity of the first product is substantially lower than that of the reference standard. We conclude that the iron product under study has a high bioavailability, an absorption mechanism equal to that of nonhemic iron, and lower toxicity than ferrous sulfate.


Assuntos
Compostos Ferrosos/farmacocinética , Análise de Variância , Animais , Disponibilidade Biológica , Composição de Medicamentos , Feminino , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/toxicidade , Absorção Intestinal , Dose Letal Mediana , Masculino , Camundongos
16.
Planta Med ; 63(6): 561-3, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9434614

RESUMO

The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) of 4-nerolidylcatechol (4-NC) and methanolic extracts of Pothomorphe umbellata and P. peltata were determined by monitoring the intensity of luminol enhanced chemiluminescence by peroxyl radicals derived from thermolysis of 2,2'-azobis(2-amidinopropane). The highest antioxidant potential was measured in the extract of P. umbellata (TRAP = 97.2 microM) while the highest reactivity was observed in the extract of P. peltata (TAR = 5.0 microM), measured as equivalents of Trolox concentration. These results were higher than those obtained for 4-NC (TRAP = 33.6 microM, TAR = 4.9 microM). DNA sugar damage induced by Fe(II) salts was also used to determine the capacity of 4-NC to suppress hydroxyl radical-mediated degradation of DNA. Calculated IC50 values for 4-NC and catechin, used as a standard, were 25 and 17 microM, respectively.


Assuntos
Catecóis/farmacologia , Dano ao DNA , Compostos Ferrosos/toxicidade , Sequestradores de Radicais Livres/farmacologia , Folhas de Planta/química , Catecóis/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação
17.
Arch Biochem Biophys ; 308(1): 158-63, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7508707

RESUMO

Isolated rat liver mitochondria exposed to Fe(II)citrate undergo lipid peroxidation and alterations in membrane proteins. These processes were associated with irreversible decrease in membrane potential and mitochondrial swelling. Lipid peroxidation was evidenced by the production of thiobarbituric acid-reactive substances and also by the reaction of these products with membrane proteins, through the formation of Schiff bases. Alterations in membrane proteins were also characterized by the loss of specific proteins that could be recovered from the mitochondrial supernatant as shown by SDS-polyacrylamide gel electrophoresis. The degree of both lipid peroxidation and alterations in membrane proteins were diminished by EGTA, ruthenium red, or dibucaine. This strongly indicates that Ca2+ potentiates the oxidative damage of mitochondria exposed to Fe(II)citrate.


Assuntos
Cálcio/farmacologia , Compostos Ferrosos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Animais , Cálcio/metabolismo , Ácido Cítrico , Sinergismo Farmacológico , Ácido Egtázico/farmacologia , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/fisiologia , Ferro/farmacologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/isolamento & purificação , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/ultraestrutura , Dilatação Mitocondrial/efeitos dos fármacos , Oniocompostos/farmacologia , Compostos Organofosforados/farmacologia , Ratos , Ratos Wistar , Rutênio Vermelho/farmacologia , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA