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1.
Foods ; 7(11)2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428616

RESUMO

The aim of this study was the monitoring of the chemical composition of olive oil at different ripening stages to determine the appropriate harvesting time during any given crop season in the northern Adriatic region. For this purpose, from September to November, two Croatian olive cultivars (Drobnica and Buza) were taken from two different olive orchards and for the respective olive oils, prepared on a laboratory scale, the major saponifiable, unsaponifiable and phenolic compounds were determined. Based on the chemical analyses performed, the optimal harvesting time has been set in October for both cultivars. Buza had a higher oleic acid, but lower total sterols, squalene and total alkanols. Compared to the local cultivars, the studied cultivars had a high total phenolic content and antioxidant activity. The antioxidant activity and concentrations of total phenols correlated with α-tocopherol in oil samples taken during the ripening progress. Finally, trace minerals detected in Buza and Drobnica oil differed, which can be an indicator of oxidative stability and authenticity of oils.

2.
Food Technol Biotechnol ; 54(2): 200-210, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27904410

RESUMO

The antioxidant activity of three types of pumpkin seed oil or oil mixtures (cold- -pressed, produced from roasted seed paste and salad) produced in the northern part of Croatia and the kinetics of their behaviour as free radical scavengers were investigated using DPPH˙. In addition, the involvement of oil tocopherol isomers (α-, γ- and δ-) in different steps of DPPH˙ disappearance and their impact on the rate of reaction were analysed. The kinetics of DPPH˙ disappearance is a two-step process. In the first step, rapid disappearance of DPPH˙ occurs during the first 11 min of the reaction, depending on the oil type, followed by a slower decline in the second step. To describe DPPH˙ disappearance kinetics, six mathematical models (mono- and biphasic) were tested. Our findings showed that γ- and δ-tocopherols affected DPPH˙ disappearance during the first step, and α-tocopherol in the second step of the reaction. Moreover, α-tocopherol demonstrated 30 times higher antioxidant activity than γ- and δ-tocopherols. The results indicated the biphasic double-exponential behaviour of DPPH˙ disappearance in oil samples, due to the complexity of reactions that involve different tocopherol isomers and proceed through different chemical pathways.

3.
Neurotoxicology ; 57: 1-12, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27570231

RESUMO

To analyze iron- and gender-dependent mechanisms possibly involved in pathogenesis of multiple sclerosis (MS) in this study we evaluated the effects of iron overload (IO) on iron status and lipid peroxidation processes (LPO) in tissues of female and male DA rats during chronic relapsing experimental autoimmune encephalomyelitis, a well-established MS animal model. Rats were treated by iron sucrose (75mg/kg bw/day) or with saline solution during two weeks before the sensitization with bovine brain homogenate in complete Freund's adjuvant. Clinical signs of EAE were monitored during 29 days. Serum and tissues of CNS and liver were sampled before immunization and at day 13th post immunization (during acute phase of EAE). The determination of ferritin, iron, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and evaluation of histopathology were performed by ELISA, ICP spectrometry and immunohistochemistry. Results showed that IO in female EAE rats accelerated the onset of disease. In contrast, in male rats it accelerated the progression of disease and increased the mortality rate. During acute phase of EAE female IO rats sequestered more Fe in the liver, spinal cord and in the brain and produced more ferritin than male EAE rats. Male rats, however, reacted on IO by higher production of MDA or 4-HNE in the neural tissues and showed greater signs of plaque formation and gliosis in spinal cord. The data point to sexual dimorphism in mechanisms that regulate peripheral and brain iron homeostasis and imply that men and women during MS might be differentially vulnerable to exogenous iron overload.


Assuntos
Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/fisiopatologia , Homeostase/imunologia , Sobrecarga de Ferro/complicações , Ferro/metabolismo , Peroxidação de Lipídeos/imunologia , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/mortalidade , Feminino , Ferritinas/sangue , Adjuvante de Freund/imunologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Medula Espinal/metabolismo
4.
Oxid Med Cell Longev ; 2016: 9191407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26925195

RESUMO

Polyphenols can act as oxidants in some conditions, inducing redox-sensitive genes. We investigated the effect of preexposure to the olive oil polyphenols extract (PFE) on time-dependent changes in the hepatic oxidative state in a model of liver regeneration-a process in which oxidative stress associated with the metabolic overload accounts for the early events that contribute to the onset of liver self-repair. Liver regeneration was induced by one-third hepatectomy in mice. Prior to hepatectomy, mice were intraperitoneally given either PFE (50 mg/kg body weight) or saline for seven consecutive days, while respective controls received vehicle alone. Redox state-regulating enzymes and thiol proteins along with the mRNA levels of Nrf2 gene and its targets γ-glutamylcysteine synthetase and heme oxygenase-1 were determined at different time intervals after hepatectomy. The liver mass restoration was calculated to assess hepatic regeneration. The resulting data demonstrate the effectiveness of preexposure to PFE in stimulating liver regeneration in a model of a small tissue loss which may be ascribed to the transient increase in oxidant load during the first hours after hepatectomy and associated induction of stress response gene-profiles under the control of Nrf2.


Assuntos
Hepatectomia , Fígado/patologia , Azeite de Oliva/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Estresse Fisiológico/genética , Animais , Antioxidantes/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Transferase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/cirurgia , Masculino , Camundongos Endogâmicos C57BL , Especificidade de Órgãos/efeitos dos fármacos , Especificidade de Órgãos/genética , Reação em Cadeia da Polimerase em Tempo Real , Estresse Fisiológico/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
5.
Arch Environ Occup Health ; 70(3): 126-32, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24965325

RESUMO

Environmental impact of natural gas facility near Molve (Podravina, Croatia) was assessed using hares (Lepus europaeus Pallas) as biomonitors. Elevated levels of heavy metals in the environment lead to their accumulation in different tissues of hares. The authors have tested accumulation and distribution of several metals in hare liver, kidney, and muscle tissues. The accumulation of copper in hare liver and kidneys with concomitant decrease of zinc was observed in animals from Podravina region as opposed to the control group of animals (Island Krk, Croatia). Secondly, the expression of metallothioneins was assessed because of their crucial role in metal homeostasis. Observed elevation of metallothionein expression in tested organs emphasizes the possible prolonged negative effects of heavy metals in the surroundings as well as a state of oxidative stress in animals. Further monitoring of the area is necessary for better control of hydrocarbon processing to diminish the possible negative environmental effects.


Assuntos
Expressão Gênica/efeitos dos fármacos , Lebres/genética , Lebres/metabolismo , Metalotioneína/genética , Metais/metabolismo , Metais/toxicidade , Campos de Petróleo e Gás , Animais , Croácia , Masculino , Metalotioneína/metabolismo , Metais/análise , Distribuição Tecidual
6.
J Appl Toxicol ; 34(3): 289-95, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23620197

RESUMO

Cadmium occurs naturally in the environment and as an anthropogenic pollutant. Exposure to low concentrations of cadmium is inevitable and may produce toxic effects. Another important aspect of cadmium toxicity is its interaction, often antagonistic, with essential elements such as selenium. The aim of this study was to highlight the risks of long-term exposure to low cadmium concentrations, using a scientific and chemical approach and hares (Lepus europaeus Pallas) as model organisms in a field study. Two study areas were monitored. Levels of cadmium and selenium were quantified in the organs of hares, the expression of metallothioneins I + II and the products of lipid peroxidation were determined. The median cadmium concentrations (wet weight) in the muscle, liver, kidney and brain of hares from an exposed group ranged from 0.033 to 0.037, 0.763 to 1.054, 3.090 to 16.594 and 0.016 to 0.087 µg g(-1), respectively; whereas, the median selenium concentrations (wet weight) ranged from 0.100 to 0.108, 0.153 to 0.332, 0.677 to 0.701 and 0.078 to 0.116 µg g(-1), respectively. Expression of the metallothioneins I + II proteins was observed in tissues. Lipid peroxidation (LPO) levels, measured as malondialdehyde (MDA) equivalents, increased with the cadmium concentration. Further research on long-term exposure to low concentrations of cadmium in the environment is needed.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Lebres/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Metalotioneína/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cádmio/farmacocinética , Croácia , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Poluentes Ambientais/farmacocinética , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Especificidade de Órgãos , Selênio/metabolismo , Fatores de Tempo , Distribuição Tecidual
7.
Histol Histopathol ; 29(3): 407-16, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24068621

RESUMO

To investigate the effects of air pollution related with the gasoline/petrochemical industry the expression of metallothionein I (MT-I) mRNA and tissue metals were analyzed in organs of mice, exposed to gasoline (G) vapor in laboratory conditions. Control groups consisted of intact mice and of those exposed in the metabolic chamber to fresh air. The data obtained by RT-PCR and inductively coupled plasma spectrometry have shown that exposure to G vapor leads to upregulation of MT-I mRNA in organs that receive a strong respiratory and olfactory input or participate in gasoline degradation and elimination (lungs, brain, kidney and liver). Besides, in the brain and in the lungs, kidney and liver a decreased tissue content of Zn²âº or Cu²âº and Mg²âº was found (p<0.001). Some of these changes were obtained also in mice closed in the metabolic chamber, pointing to the involvement of stress-induced mechanisms in the transcriptional regulation of MTs.


Assuntos
Poluição do Ar/efeitos adversos , Gasolina/efeitos adversos , Metalotioneína/biossíntese , Animais , Química Encefálica , Cobre/análise , Rim/química , Rim/patologia , Fígado/química , Fígado/patologia , Pulmão/química , Pulmão/patologia , Magnésio/análise , Metalotioneína/análise , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrofotometria Atômica , Zinco/análise
8.
J Environ Sci Health B ; 48(11): 906-18, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23998302

RESUMO

In the present laboratory study, persistence of imidacloprid (IMI) as a function of initial insecticide concentration and soil properties in two Croatian soils (Krk sandy clay and Istria clay soils) was studied and described mathematically. Upon fitting the obtained experimental data for the higher concentration level (5 mg/kg) to mathematical models, statistical parameters (R (2), scaled root mean squared error and χ (2) error) indicated that the single first-order kinetics model provided the best prediction of IMI degradation in the Krk sandy clay soil, while in the Istria clay soil biphasic degradation was observed. At the lower concentration level (0.5 mg/kg), the biphasic models Gustafson and Holden models as well as the first-order double exponential model fitted the best experimental data in both soils. The disappearance time (DT50) values estimated by the single first-order double exponential model (from 50 to 132 days) proved that IMI can be categorized as a moderately persistent pesticide. In the Krk sandy clay soil, resulting DT50 values tended to increase with an increase of initial IMI concentration, while in the Istria clay soil, IMI persistence did not depend on the concentration. Organic matter of both experimental soils provided an accelerating effect on the degradation rate. The logistic model demonstrated that the effect of microbial activity was not the most important parameter for the biodegradation of IMI in the Istria clay soil, where IMI degradation could be dominated by chemical processes, such as chemical hydrolysis. The results pointed that mathematical modeling could be considered as the most convenient tool for predicting IMI persistence and contributes to the establishment of adequate monitoring of IMI residues in contaminated soil. Furthermore, IMI usage should be strictly controlled, especially in soils with low organic matter content where the risk of soil and groundwater contamination is much higher due to its longer persistence and consequent leaching and/or moving from soil surface prior to its degradation.


Assuntos
Imidazóis/metabolismo , Inseticidas/metabolismo , Nitrocompostos/metabolismo , Poluentes do Solo/metabolismo , Solo/química , Cromatografia Líquida de Alta Pressão , Croácia , Relação Dose-Resposta a Droga , Monitoramento Ambiental , Imidazóis/química , Inseticidas/química , Cinética , Modelos Teóricos , Neonicotinoides , Nitrocompostos/química , Poluentes do Solo/química
9.
Curr Aging Sci ; 6(1): 37-44, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23895520

RESUMO

Metallothioneins (MTs) are small, cysteine-rich proteins which have been implicated in various forms of stress providing cytoprotective action against oxidative injury, DNA damage and apoptosis. Owing to their high affinity for physiological metals, such as zinc and copper MTs are also critical components of regulatory proteins involved in cell growth and multiplication, as well as in the maintenance of immune homeostasis. To elucidate the role of MTs in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MT I+II proteins and the content of free Zn ions in the brain, spinal cord and in the liver early in the course of chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) pathogenesis, i.e. before the onset of any clinical symptoms. Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control animals were treated with CFA alone. The data, obtained by immuno-histochemistry and in situ fluorescent labeling of free zinc ions, have shown that in the presymptomatic phase of CR-EAE (on the seventh postimmunization day) MTs I+II were markedly upregulated in the cells that form blood-brain and blood-cerebrospinal fluid barriers, as well as in the cerebellar parenchyma and hippocampal dentate gyri. Furthermore, we found that the liver also becomes a site of extensive MTs I+II synthesis shortly after immunization. Simultaneously, tissue content of free zinc ions increased at the sites of MTs induction, reflecting their antioxidative activity. The data, described in this paper point to regulatory and neuroprotective role of MTs in the pathogenesis of CR-EAE.


Assuntos
Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Metalotioneína/metabolismo , Animais , Barreira Hematoencefálica , Encéfalo/metabolismo , Encéfalo/patologia , Bovinos , Encefalomielite Autoimune Experimental/patologia , Imuno-Histoquímica , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Fatores de Tempo , Regulação para Cima , Zinco/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-23705608

RESUMO

The aim of this study was to analyze and evaluate risks of long-term exposure to mercury in hares (Lepus europaeus Pallas), with a chemical-analytical approach evaluating median mass fraction of toxic mercury in the hares organs (liver, kidney, muscle and brain). To obtain better insight into possible effects of mercury, the study included screening of the oxidative status after long term exposure to low concentrations of mercury. Hares organs were analyzed for total mercury concentration by AAS. Glutathione and glutathione-dependent enzymes status was also investigated. The median mercury concentrations (wet weight) in the liver, kidney, muscle and brain of the hares ranged from 0.058-0.189, 0.138-0.406, 0.013-0.046 and 0.022-0.102 µg/g respectively. Concentration of the glutathione (GSH), glutathione-peroxidase (GPx), and glutathione-reductase (GR) activity increased with the mercury concentration. However, glutathione S-transferase (GST) and superoxide-dismutase (SOD) activity decreased with the mercury concentration. The results of this study show the impact of environmentally absorbed mercury on the antioxidant status of the examined hares. Further research on long-term exposure to low concentrations of mercury is needed.


Assuntos
Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa/metabolismo , Mercúrio/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lebres , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo
11.
Neuroimmunomodulation ; 20(3): 152-63, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23485922

RESUMO

OBJECTIVES: Compared to the Dark Agouti (DA), the Albino Oxford (AO) rat strain exhibits lower susceptibility to the induction of experimental autoimmune encephalomyelitis (EAE). Here, we investigated the potential contribution of the heavy metal-binding proteins metallothioneins (MTs) I/II to these effects. METHODS: Rats were immunized with bovine brain homogenate emulsified in complete Freund's adjuvant or only with complete Freund's adjuvant. The expression patterns of MTs mRNA and proteins and tissue concentrations of Zn2+ and Cu2+ were estimated in the brain and in the liver on days 7 and 12 after immunization, by real-time PCR, immunohistochemistry and inductively coupled plasma spectrometry, respectively. Additionally, the hepatic transforming growth factor beta and nuclear factor kappa B immunoreactivities were tested. RESULTS: Clinical signs of EAE were not induced in AO rats, but they upregulated the expression of MT I/II proteins in the brain (hippocampus and cerebellum) and in the liver, similarly as DA rats. The transcriptional activation of MT-I occurred, however, only in DA rats, which accumulated also more zinc in the brain and in the liver. In contrast, intact AO rats had greater hepatic MT-I mRNA immunoreactivity and more Cu2+ in the hippocampus. Besides, in immunized AO rats a high upregulation of transforming growth factor beta and nuclear factor kappa B immunoreactivities was found in several hepatic structures (vascular endothelium, Kupffer cells and hepatocytes). CONCLUSIONS: Our data show that AO and DA rats differ in constitutive and inductive MT-I gene expression in the brain and in the liver, as well as in the hepatic cytokine profile, suggesting that these mechanisms may contribute to the discrepancy in the susceptibility to EAE.


Assuntos
Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/metabolismo , Regulação da Expressão Gênica/imunologia , Predisposição Genética para Doença , Metalotioneína/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/patologia , Adjuvante de Freund/toxicidade , Masculino , Metalotioneína/genética , RNA Mensageiro/metabolismo , Ratos , Especificidade da Espécie , Estatísticas não Paramétricas , Linfócitos T/metabolismo , Linfócitos T/patologia , Fatores de Tempo
12.
Clin Dev Immunol ; 2013: 750406, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24489578

RESUMO

In a search of peripheral factors that could be responsible for the discrepancy in susceptibility to EAE in Albino Oxford (AO) and Dark Agouti (DA) rats, we estimated the expression of metallothioneins I/II (MT), heat shock protein-gp96, interleukin (IL)-6, and transforming growth factor (TGF)- ß in the livers of these animals. Rats were immunized with bovine brain homogenate (BBH) emulsified in complete Freund adjuvant (CFA) or only with CFA. Western blot and immunohistochemical analyses were done on day 12 after the immunization, as well as in intact rats. The data have shown that during the first attack of EAE only the EAE prone-DA rats markedly upregulated the hepatic MTs, gp96, IL-6, and TGF- ß . In contrast, AO rats had a significantly higher expression of MT I/II, IL-6, and TGF- ß in intact liver (P < 0,001), suggesting that the greater constitutive expression of these proteins contributed to the resistance of EAE. Besides, since previously we found that AO rats reacted on immunization by an early upregulation of TGF- ß on several hepatic structures (vascular endothelium, Kupffer cells, and hepatocytes), the data suggest that the specific hepatic microenvironment might contribute also to the faster recovery of these rats from EAE.


Assuntos
Antígenos de Neoplasias/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Interleucina-6/metabolismo , Fígado/metabolismo , Metalotioneína/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Antígenos de Neoplasias/genética , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/genética , Expressão Gênica , Glicoproteínas/metabolismo , Interleucina-6/genética , Masculino , Metalotioneína/genética , Ratos , Fator de Crescimento Transformador beta/genética
13.
J Environ Sci Health B ; 47(8): 779-94, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22575005

RESUMO

Sorption-desorption behavior of imidacloprid in six soils collected from five coastal regions in Croatia at 20, 30 and 40°C was investigated using batch equilibrium technique. Isothermal data were applied to Freundlich, Langmuir and Temkin equations, and the thermodynamic parameters ΔH°, ΔG°, ΔS° were calculated. The sorption isotherm curves were non-linear and may be classified as L-type, suggesting a relatively high sorption capacity for imidacloprid. Our results showed that the K( sor ) ( F ) values decreased for all the tested soils as the temperature increased, indicating that the temperature strongly influences the sorption. Values of ΔG° were negative (-4.65 to -2.00 kJ/mol) indicating that at all experimental temperatures the interactions of imidacloprid with soils were spontaneous processes. The negative and small ΔH° values (-19.79 to -8.89 kJ/mol) were in the range of weak forces, such as H-bonds, consistent with interactions and partitioning of the imidacloprid molecules into soil organic matter. The ΔS° values followed the range of -57.12 to -14.51 J/molK, suggesting that imidacloprid molecules lose entropy during transition from the solution phase to soil surface. It was found that imidacloprid desorption from soil was concentration and temperature-dependent, i.e. at lower imidacloprid concentrations and temperature, lower desorption percentage occurred. Desorption studies revealed that hysteretic behavior under different temperature treatments existed, and it was more pronounced at 20°C in the soils with higher OC content. The study results emphasize the importance of thermodynamic parameters in controlling soil pesticide mobility in different geographical locations, seasons and greenhouse conditions.


Assuntos
Herbicidas/química , Imidazóis/química , Nitrocompostos/química , Poluentes do Solo/química , Adsorção , Croácia , Cinética , Neonicotinoides , Temperatura
14.
Coll Antropol ; 35 Suppl 1: 85-91, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21648316

RESUMO

The aim of this study was to investigate the influence of olive oil (00) enriched diet on the lipid content of mice brain during the early phase of liver regeneration and to test a relationship of these changes with calcium content. C57BI mice were fed over 21 days with diet enriched with olive oil, containing predominantly oleic acid (18:1n-9). The animals were one-third partially hepatectomised (pHx) under aether anaesthesia. Total lipids were extracted from tissue samples with a chloroform-methanol (2:1, v/v) mixture according to Folch et al. Mineral concentration was determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES) after microwave brain tissue digestion. The diet containing 00 increased both total lipid content and the calcium concentration in brain during the early phase of liver regeneration (12hrs post pHx), suggesting that monounsaturated oleic acid might interact with some metal-dependent activities that control changes in the brain during liver regeneration.


Assuntos
Química Encefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cálcio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Regeneração Hepática/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Encéfalo/metabolismo , Hepatectomia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Azeite de Oliva , Tamanho do Órgão/efeitos dos fármacos
15.
Biol Trace Elem Res ; 143(1): 332-43, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20845085

RESUMO

To elucidate the role of iron in the pathomechanisms of autoimmune CNS disorders, we estimated the tissue concentrations of Fe(2+) in the brain, spinal cord, and liver in the chronic relapsing form of experimental autoimmune encephalomyelitis (EAE). The disease was induced in Dark Agouti (DA) strain of rats, by subcutaneous injection of bovine brain homogenate in complete Freund's adjuvant (CFA). Control rats consisted of unsensitized rats and of rats treated with CFA or saline. The data obtained by clinical assessment and by inductively coupled plasma spectrometry have shown that the attacks of disease (on the 12th and 22nd post-immunization day) were followed by high accumulation of iron in the liver. Additionally, during the second attack of disease, the decreased concentration of Fe(2+) was found in cervical spinal cord. The data point to regulatory effects of iron and hepatic trace elements regulating mechanisms in the pathogenesis of EAE.


Assuntos
Encefalomielite Autoimune Experimental/metabolismo , Ferro/metabolismo , Animais , Encéfalo/metabolismo , Fígado/metabolismo , Masculino , Ratos , Medula Espinal/metabolismo
16.
Histol Histopathol ; 26(2): 233-45, 2011 02.
Artigo em Inglês | MEDLINE | ID: mdl-21154237

RESUMO

To elucidate the role of metallothioneins (MTs) in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MTs I+II and the tissue concentrations of Zn²+ and Cu²+ in the brain, spinal cord (SC) and in the liver during the periods of attacks and remissions in chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE). Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control rats were treated with CFA. The data, obtained by clinical assessment, immunohistochemistry and inductivity coupled plasma spectrometry, have shown that during the first attack (on the 12th day) MTs I+II were markedly upregulated in subarachnoid regions and perivascular space on astrocytes, microglia and on spinal neurons. Simultaneously, the concentrations of zinc in the SC and zinc and copper in the liver have found to be increased. During the second attack (on the 22nd day) a new overexpression of MTs was found in the cerebellum, in sulcus hippocampi, in spinal neurons and particularly in hepatocytes around the central vein. Concomitantly, in the brain and SC the concentration of copper increased. The data point to a neuroprotective role of MTs and to an important regulatory role of essential metals and hepatic MTs in the pathogenesis of CR-EAE.


Assuntos
Cobre/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Metalotioneína/metabolismo , Zinco/metabolismo , Animais , Bovinos , Sistema Nervoso Central/química , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Doença Crônica , Cobre/análise , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Imuno-Histoquímica , Fígado/química , Fígado/metabolismo , Fígado/patologia , Ratos , Ratos Endogâmicos , Recidiva , Espectrofotometria Atômica , Fatores de Tempo , Zinco/análise
17.
Exp Toxicol Pathol ; 61(6): 581-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19186041

RESUMO

Carbon tetrachloride (CCl(4)) is a well-known model compound for producing chemical hepatic injury. This study investigated the protective effects of the flavonoid luteolin on the CCl(4)-induced hepatotoxicity in mice. Luteolin dissolved in dimethyl sulfoxide (DMSO) was administered intraperitoneally (i.p.) at 5 or 50 mg/kg as a single dose, and once daily for 2 consecutive days. Two hours after the final treatment, the mice were treated with CCl(4) (20 mg/kg, i.p.). CCl(4)-induced hepatotoxicity was reduced in a dose- and time-dependent manner, as determined by decreased serum aminotransferase activities and liver histopathology. CCl(4) intoxication resulted in an overexpression of heat shock protein gp96 in the mice liver, which was strongly attenuated by luteolin pretreatment. Luteolin has also decreased oxidative stress produced by CCl(4), as suggested by improvement in the Cu/Zn superoxide dismutase activity. The effect of luteolin on myeloperoxidase, an indicator of inflammatory cell infiltration, was also investigated. Treatment of the mice with luteolin resulted in a significant decrease in the myeloperoxidase activity. The hepatoprotective effect of luteolin against CCl(4) hepatotoxicity was higher in animals pretreated with luteolin for 2 consecutive days. This suggests that the protection might be due to induction of some adaptive mechanisms. The data indicate that luteolin could be effective in protecting mice from the hepatotoxicity produced by CCl(4).


Assuntos
Tetracloreto de Carbono/toxicidade , Fígado/efeitos dos fármacos , Luteolina/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Tempo
18.
Nutr Res ; 28(4): 263-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19083418

RESUMO

The influence of dietary fats on cellular alpha-tocopherol and retinol uptake in iron overload is poorly understood. The aim of this study was to investigate the effect of a high-iron diet on the retinol and alpha-tocopherol levels in mice fed olive oil- and corn oil-enriched diets. Mice were fed for 3 weeks a standard mouse chow (the control group) and diets enriched with 5% by weight of corn oil or olive oil. Diets of the mice fed corn oil and olive oil were additionally supplemented with 1% by weight carbonyl iron. Both dietary oils and iron increased the liver iron uptake. High-iron feeding induced oxidative stress in mice liver, measured as a thiobarbituric acid-reactive substance level. Both fats and iron induced changes in the liver fatty acid composition. Liver retinol and alpha-tocopherol stores increased with iron supplementation in the olive oil-enriched diet, with a simultaneous decrease in serum. The results suggest that the influx of alpha-tocopherol and retinol from serum to the liver is induced by high dietary iron. This redistribution appears to be stronger for retinol than for alpha-tocopherol and is also higher in mice fed olive oil than in mice fed corn oil, suggesting that the composition of dietary lipids is important in the treatment of high-iron tissue conditions. In conclusion, the results of this study suggest that the increase of hepatic alpha-tocopherol and retinol levels in the olive oil-based diet is a dietary-dependent responsive mechanism that probably is not primarily related to an increased risk of oxidative damage induced by high-iron intake.


Assuntos
Ácidos Graxos/metabolismo , Ferro da Dieta/farmacologia , Fígado/metabolismo , Vitamina A/metabolismo , alfa-Tocoferol/metabolismo , Animais , Óleo de Milho/administração & dosagem , Ácidos Graxos/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Azeite de Oliva , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Distribuição Aleatória , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina A/sangue , alfa-Tocoferol/sangue
19.
Biol Trace Elem Res ; 126(1-3): 176-85, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18649050

RESUMO

The aim of this study was to investigate the protective effect of luteolin on liver Ca, Mg, Zn, Cu, Fe, and Mn content in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. Additionally, liver metallothionein (MT) expression was studied. Luteolin was administered intraperitoneally (i.p.) as a single 5- or 50-mg/kg dose or once daily for two consecutive days, respectively. Two hours after the last injection, the mice were treated with CCl4 (20 mg/kg, i.p.). CCl4 injection reduced hepatic level of all metals except Ca, with an intense cytoplasmic staining pattern in hepatocytes located in periportal areas, indicating induction of MTs. Pretreatment with 50 mg/kg of luteolin for 2 days remarkably elevated metal content to control values (Mg and Cu) or even above them (Zn and Fe). Luteolin pretreatment increased pericentral MTs immunopositivity and histological architecture improvement in a time- and dose-dependent manner, being the most prominent in mice pretreated with 50 mg/kg for 2 days. The liver in this group showed pronounced MT expression in almost all hepatocytes throughout the liver parenchyma. In conclusion, these results suggest the protective effect of luteolin on CCl4-induced hepatotoxicity and an enhancement of hepatocyte proliferative capabilities.


Assuntos
Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Luteolina/farmacologia , Metalotioneína/metabolismo , Metais/metabolismo , Animais , Cobre/metabolismo , Imuno-Histoquímica , Ferro/metabolismo , Magnésio/metabolismo , Masculino , Manganês/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Zinco/metabolismo
20.
Acta Med Hist Adriat ; 6(2): 309-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-20102252

RESUMO

Professor Eugen Cerkovnikov, PhD (Kamenska, Russia, 1904- Rijeka, Croatia 1985) graduated in chemical technology from the Faculty of Engineering in Zagreb in 1929. His first job was at the School of Medicine in Paris in 1930, and then he moved to Zagreb to the Department of Organic Chemistry of the Faculty of Engineering run by our Nobel Prize winner Vladimir Prelog (1935-1938). There he took his PhD degree with a dissertation on piperidine gamma derivatives. From 1938 to 1947 he was a research associate at an institute established by the pharmaceutical company Kastel (later Pliva). This is when he became a lecturer at the Faculty of Pharmacy in Zagreb and the first director of the Institute of Organic Chemistry, established in 1946/47. In 1948 he became reader, and in 1956 (full) professor. In 1957 he moved to the newly established School of Medicine in Rijeka, and set up the Institute of Chemistry and Biochemistry. He ran the Institute until retirement in 1975. He was the second dean of the Rijeka University School of Medicine and a pioneer of quantum chemistry and medical cybernetics in undergraduate and (post)graduate courses. His scientific work consists of over 200 papers published at home and abroad, 60 professional papers, 20 book reviews, three works of translation, and 27 volumes of lecture notes. In 1958, professor Cerkovnikov established the Croatian Chemical Society and the Rijeka and Istria branches of the nation's Association of Chemists and Chemical Engineers, chairing them until 1974. In addition, he was one of the founding fathers, and the first chair of the Health Culture Studies Association in Rijeka (that preceded today's Croatian Scientific Society for the History of Health Culture), established in 1965.

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