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1.
Chemosphere ; 363: 142925, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39053782

RESUMEN

In the context of increasing environmental contamination, our study employed fish as bioindicators, focusing on non-invasive cortisol measurements in scales and fins in response to severe PFAS pollution in the Veneto area of Italy. Our preliminary findings showed species-specific stress responses, as observed in Squalius cephalus and Padogobius bonelli, suggesting the need for broader biomonitoring to capture the complex impact of environmental stressors on aquatic organisms. Moreover, due to the unusual characteristics of the rivers selected for the biomonitoring activity, a possible link between PFAS exposure and cortisol levels in S. cephalus demonstrates the method's potential.


Asunto(s)
Monitoreo del Ambiente , Peces , Hidrocortisona , Ríos , Estrés Fisiológico , Contaminantes Químicos del Agua , Animales , Hidrocortisona/análisis , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Ríos/química , Italia , Peces/metabolismo , Fluorocarburos/toxicidad , Fluorocarburos/análisis , Especificidad de la Especie , Monitoreo Biológico
2.
Antioxidants (Basel) ; 12(2)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36829911

RESUMEN

Antarctica is the continent with the lowest local human impact; however, it is susceptible to pollution from external sources. Emerging pollutants such as perfluoroalkyl substances pose an increasing threat to this environment and therefore require more in-depth investigations to understand their environmental fate and biological impacts. The present study focuses on expression analysis at the transcriptional level of genes coding for four antioxidant enzymes (sod1, sod2, gpx1, and gpx4) in the liver and kidney of an Antarctic fish species, Trematomus newnesi (Boulenger, 1902). mRNA levels were also assessed in fish exposed to 1.5 µg/L of perfluoro-octanoic acid for 10 days. The kidney showed a higher level of expression than the liver in wildlife specimens. In the liver, the treatment induced an increase in gene expression for all the considered enzymes, whereas in the kidney, it induced a general decrease. The obtained results advance the scientific community's understanding of how the potential future presence of anthropogenic contaminants in the Southern Ocean can affect the antioxidant system of Antarctic fishes. The presence of pollutants belonging to the perfluoroalkyl substances in the Southern Ocean needs to be continuously monitored in parallel with this type of research.

3.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-36361591

RESUMEN

Metal bioaccumulation and metallothionein (MT) expression were investigated in the gills and liver of the red-blooded Antarctic teleost Trematomus hansoni to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper and cadmium concentrations in its tissues. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory conditions. The two treatments led to a significant accumulation of both metals and increased gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in specimens exposed to Cd, but most of these proteins were soon oxidized, probably because they were involved in cell protection against oxidative stress risk by scavenging reactive oxygen species. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species that evolved in an environment characterized by naturally high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming more toxic every day.


Asunto(s)
Perciformes , Contaminantes Químicos del Agua , Animales , Metalotioneína/genética , Metalotioneína/metabolismo , Cadmio/toxicidad , Cadmio/análisis , Perciformes/genética , Perciformes/metabolismo , Branquias/metabolismo , Cobre/toxicidad , Cobre/análisis , Metales/toxicidad , Intoxicación por Metales Pesados , Peces/metabolismo , Contaminantes Químicos del Agua/toxicidad
4.
Int J Mol Sci ; 23(19)2022 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-36233302

RESUMEN

This work aimed to evaluate the effects of zinc (Zn) relating to cadmium (Cd)-induced toxicity and the role played by MTF-1. This transcription factor regulates the expression of genes encoding metallothioneins (MTs), some Zn transporters and the heavy chain of γ-glutamylcysteine synthetase. For this reason, two cell lines of mouse fibroblasts were used: a wild-type strain and a knockout strain to study the effects. Cells were exposed to complete medium containing: (1) 50 µM ZnSO4 (Zn), (2) 1 µM CdCl2 (Cd 1), (3) 2 µM CdCl2 (Cd 2), (4) 50 µM ZnSO4 + 1 µM CdCl2 (ZnCd 1) and (5) 50 µM ZnSO4 + 2 µM CdCl2 (ZnCd 2) for 4, 18 and 24 h. Following exposure, cell viability, the intracellular content of metals, glutathione (GSH) and MT and the gene expression of the two isoforms of MT was evaluated. The results obtained suggest that a lower Cd content in the co-treatments is responsible for the protection offered by Zn due to the probable competition for a common transporter. Furthermore, Zn determines an increase in GSH in co-treatments compared to treatments with Cd alone. Finally, the MTF-1 factor is essential for the expression of MT-1 but not of MT-2 nor probably for the heavy chain of γ-glutamylcysteine synthetase.


Asunto(s)
Intoxicación por Cadmio , Cadmio , Animales , Cadmio/metabolismo , Fibroblastos/metabolismo , Glutamato-Cisteína Ligasa/genética , Glutatión/farmacología , Metalotioneína/metabolismo , Ratones , Factores de Transcripción/metabolismo , Zinc/farmacología
5.
Antioxidants (Basel) ; 11(6)2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35740012

RESUMEN

In recent decades, the interest in PFAS has grown exponentially around the world, due to the toxic effects induced by these chemical compounds in humans, as well as in other animals and plants. However, current knowledge related to the antistress responses that organisms can express when exposed to these substances is still insufficient and, therefore, requires further investigation. The present study focuses on antioxidant responses in Squalius cephalus and Padogobius bonelli, exposed to significant levels of PFAS in an area of the Veneto Region subjected to a recent relevant pollution case. These two ubiquitous freshwater species were sampled in three rivers characterised by different concentrations of PFAS. Several biomarkers of oxidative stress were evaluated, and the results suggest that PFAS chronic exposure induces some physiological responses in the target species, at both cellular and tissue scales. The risk of oxidative stress seems to be kept under control by the antioxidant system by means of gene activation at the mitochondrial level. Moreover, the histological analysis suggests an interesting protective mechanism against damage to the protein component based on lipid vacuolisation.

6.
Antioxidants (Basel) ; 10(4)2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33918542

RESUMEN

It is well known that the excessive production of reactive oxygen species (ROS) can lead to the peroxidation of membrane lipids, glycation/oxidation/nitration of proteins, inactivation of enzymes, DNA mutation and damage, and other alterations in the subcellular components [...].

7.
Artículo en Inglés | MEDLINE | ID: mdl-33022382

RESUMEN

The exposure to metals is known to generate oxidative stress in living organisms, which can result in the induction of protective antioxidant defences, both enzymatic and non-enzymatic. This work aims to obtain new data on the existing links among several non-enzymatic components of the antioxidant system, that are physiologically related to both metal sequestration and defense against metal-induced oxidative stress, using the blue mussels (Mytilus galloprovincialis) as a model organism. Specimens of this marine bivalve were experimentally exposed to cadmium (Cd), used as oxidative stress inducer. Cd, metallothionein (MT), glutathione (GSH), malondialdehyde (MDA) contents, and glutathione reductase (GR) activity in gills and in digestive glands were assessed at 0, 12, 24, 48, 72 and 96 h. The obtained results provide new data about the relationships among the non-enzymatic antioxidant cellular components considered in this study. These constitute the prompt physiological responses to the oxidative stress in blue mussels exposed to Cd in controlled laboratory conditions.


Asunto(s)
Antioxidantes/metabolismo , Cadmio/toxicidad , Mytilus/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Branquias/efectos de los fármacos , Branquias/metabolismo , Glutatión/metabolismo , Glutatión Reductasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Metalotioneína/metabolismo , Metales/toxicidad , Contaminantes Químicos del Agua/toxicidad
8.
Artículo en Inglés | MEDLINE | ID: mdl-33143342

RESUMEN

Due to their unique properties, perfluorinated substances (PFAS) are widely used in multiple industrial and commercial applications, but they are toxic for animals, humans included. This review presents some available data on the PFAS environmental distribution in the world, and in particular in Europe and in the Veneto region of Italy, where it has become a serious problem for human health. The consumption of contaminated food and drinking water is considered one of the major source of exposure for humans. Worldwide epidemiological studies report the negative effects that PFAS have on human health, due to environmental pollution, including infertility, steroid hormone perturbation, thyroid, liver and kidney disorders, and metabolic disfunctions. In vitro and in vivo researches correlated PFAS exposure to oxidative stress effects (in mammals as well as in other vertebrates of human interest), produced by a PFAS-induced increase of reactive oxygen species formation. The cellular antioxidant defense system is activated by PFAS, but it is only partially able to avoid the oxidative damage to biomolecules.


Asunto(s)
Contaminación Ambiental , Fluorocarburos , Contaminantes Químicos del Agua , Animales , Antioxidantes , Salud Ambiental , Europa (Continente) , Fluorocarburos/análisis , Fluorocarburos/toxicidad , Humanos , Italia , Estrés Oxidativo , Vertebrados , Contaminantes Químicos del Agua/análisis
9.
Antioxidants (Basel) ; 9(10)2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33023127

RESUMEN

Glutathione peroxidases (GPxs) form a broad family of antioxidant proteins essential for maintaining redox homeostasis in eukaryotic cells. In this study, we used an integrative approach that combines bioinformatics, molecular biology, and biochemistry to investigate the role of GPxs in reactive oxygen species detoxification in the unicellular eukaryotic model organism Tetrahymena thermophila. Both phylogenetic and mechanistic empirical model analyses provided indications about the evolutionary relationships among the GPXs of Tetrahymena and the orthologous enzymes of phylogenetically related species. In-silico gene characterization and text mining were used to predict the functional relationships between GPxs and other physiologically-relevant processes. The GPx genes contain conserved transcriptional regulatory elements in the promoter region, which suggest that transcription is under tight control of specialized signaling pathways. The bioinformatic findings were next experimentally validated by studying the time course of gene transcription and enzymatic activity after copper (Cu) exposure. Results emphasize the role of GPxs in the detoxification pathways that, by complex regulation of GPx gene expression, enable Tethraymena to survive in high Cu concentrations and the associated redox environment.

10.
Antioxidants (Basel) ; 9(4)2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32316382

RESUMEN

In the present study, we describe the purification and molecular characterization of Cu,Zn superoxide dismutase (SOD) from Chionodraco hamatus, an Antarctic teleost widely distributed in many areas of the Ross Sea that plays a pivotal role in the Antarctic food chain. The primary sequence was obtained using biochemical and molecular biology approaches and compared with Cu,Zn SODs from other organisms. Multiple sequence alignment using the amino acid sequence revealed that Cu,Zn SOD showed considerable sequence similarity with its orthologues from various vertebrate species, but also some specific substitutions directly linked to cold adaptation. Phylogenetic analyses presented the monophyletic status of Antartic Teleostei among the Perciformes, confirming the erratic differentiation of these proteins and concurring with the theory of the "unclock-like" behavior of Cu,Zn SOD evolution. Expression of C. hamatus Cu,Zn SOD at both the mRNA and protein levels were analyzed in various tissues, highlighting the regulation of gene expression related to environmental stress conditions and also animal physiology. The data presented are the first on the antioxidant enzymes of a fish belonging to the Channichthyidae family and represent an important starting point in understanding the antioxidant systems of these organisms that are subject to constant risk of oxidative stress.

11.
J Pept Sci ; 24(7): e3089, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29808604

RESUMEN

Cathelicidins are an important family of antimicrobial peptide effectors of innate immunity in vertebrates. Two members of this group, CATH-1 and CATH-2, have been identified and characterized in teleosts (ray-finned fish). In this study, we investigated the expression of these genes in different tissues of rainbow trout challenged with 4 different inactivated pathogens. By using qPCR, we detected a strong induction of both cath-1 and cath-2 genes within 24 hours after intraperitoneal inoculation with Lactococcus garvieae, Yersinia ruckeri, Aeromonas salmonicida, or Flavobacterium psychrophilum cells. Up to 700-fold induction of cath-2 was observed in the spleen of animals challenged with Y. ruckeri. Moreover, we found differences in the intensity and timing of gene up-regulation in the analyzed tissues. The overall results highlight the importance of cathelicidins in the immune response mechanisms of salmonids.


Asunto(s)
Aeromonas salmonicida/inmunología , Catelicidinas/inmunología , Flavobacterium/inmunología , Lactococcus/inmunología , Oncorhynchus mykiss/microbiología , Yersinia ruckeri/inmunología , Aeromonas salmonicida/citología , Animales , Antibacterianos/química , Antibacterianos/metabolismo , Catelicidinas/biosíntesis , Catelicidinas/genética , Relación Dosis-Respuesta a Droga , Flavobacterium/citología , Perfilación de la Expresión Génica , Lactococcus/citología , Pruebas de Sensibilidad Microbiana , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/inmunología , Bazo/inmunología , Bazo/microbiología , Relación Estructura-Actividad , Yersinia ruckeri/citología
12.
Artículo en Inglés | MEDLINE | ID: mdl-26122313

RESUMEN

Filter feeding animals can accumulate large amount of contaminants in their body through particles filtered from seawater. In particular, copper is interesting since it plays important roles as co-factor of numerous proteins but its toxicity is well established, also because it can readily generate free radicals or oxidize cellular components through their redox activity. Its availability is tightly regulated within cells: it is immediately transferred to metallothionein (MT) that in turn provides efficient and specific mechanisms for its intracellular storage and transport. The aim of this study was to evaluate the acute effect of sublethal copper concentrations in Venerupis philippinarum, by studying the kinetics of copper, zinc (for its interactions at the sites of intake or elimination with the accumulation of other essential and not essential trace metals) and metallothionein accumulation under laboratory conditions. The time-course of metal accumulation/elimination is similar in digestive gland and gills and importantly it is dose-dependent. Both copper and zinc increase slowly within cells, reaching a maximum concentration at the end of the exposure period. During the detoxification period, the metal levels in digestive gland and gills rapidly decrease, with different kinetics in the two tissues. Positive correlations between metallothionein accumulation and copper or zinc concentrations have been verified in both treated groups. The obtained data demonstrated the involvement of MTs in detoxification strategies after a recovery period in clean seawater.


Asunto(s)
Bivalvos/metabolismo , Cobre/metabolismo , Metalotioneína/metabolismo , Distribución Tisular/fisiología , Zinc/metabolismo , Animales , Cobre/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Branquias/metabolismo , Cinética , Región Mediterránea , Agua de Mar/química , Mariscos , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Zinc/toxicidad
13.
J Appl Toxicol ; 33(7): 527-36, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23401182

RESUMEN

Metals can directly or indirectly cause an increase in reactive oxygen species (ROS) accumulation in cells, and this may result in programmed cell death. A number of previous studies have shown that zinc (Zn) modulates mitogenic activity via several signalling pathways, such as AKT, mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF -κB), AP-1 and p53. The exact role that Zn plays in the regulation of apoptosis remains ambiguous. Intracellular free Zn modulates p53 activity and stability, and excess Zn alters the p53 protein structure and down-regulates p53's binding to DNA. Copper (Cu) accumulation causes apoptosis that seems to be mediated by DNA damage and subsequent p53 activation. Cu can also displace Zn from its normal binding site on p53, resulting in abnormal protein folding and disruption of p53 function. In spite of the induction of the tumour suppressor p53, hepatic Cu accumulation significantly increases the risk of cancerous neoplasm both in humans and rats, suggesting that p53 function may be impaired in these cells. It is generally understood that imbalances in Cu and Zn levels may lead to a higher prevalence of p53 mutations. An increased number of p53 mutations have been found in liver samples from Wilson's disease (WD) patients. High levels of the p53 mutation most probably contribute to the pathogenesis of cancer in individuals with WD, but the cause and effect are not clear. The protein p53 also plays a crucial role in the transcriptional regulation of metallothionein, which indicates a novel regulatory role for p53. This review discusses the central role of p53 and the redox-inert metal Zn in the cellular stress responses induced by the redox active biometal Cu.


Asunto(s)
Cobre/toxicidad , Estrés Oxidativo/efectos de los fármacos , Proteína p53 Supresora de Tumor/fisiología , Zinc/farmacología , Animales , Cobre/metabolismo , Genes p53 , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/metabolismo , Humanos , Metalotioneína/metabolismo , Radioterapia , Proteína p53 Supresora de Tumor/genética , Zinc/metabolismo
14.
Artículo en Inglés | MEDLINE | ID: mdl-22309987

RESUMEN

The main characteristic of Antarctic seawater is its low constant temperature and its high concentration of O(2), which can increase the formation rate of reactive oxygen species (ROS), together with a natural occurrence of elevated cadmium and copper levels. In the present paper, we studied the presence of cadmium, copper and zinc, metallothioneins (MTs) and glutathione (GSH), and antioxidant enzyme activities in the Antarctic teleosts Trematomus bernacchii and Trematomus newnesi, in order to determine the influence of the peculiar physico-chemical features of the Antarctic marine environment on these physiological defence systems in two species of teleosts. In both of them, cadmium and copper accumulation occurs mostly in the liver. T. bernacchii accumulates zinc mostly in the hepatic tissue, whereas T. newnesi does not show a preferential accumulation site. In addition to the intra-specific analysis, we decided to compare the two species of the Trematomus genus in order to verify if the different feeding habits and motility of these fish affects metal accumulation. Our results show that the liver of T. bernacchii accumulates cadmium and zinc at a higher extent with respect to T. newnesi. Glutathione (GSH) and metallothioneins (MTs) are present in great quantity in the liver of both species. Moreover liver is the tissue which generally showed the highest antioxidant enzyme levels. The results provide further insights in the physiological mechanisms evolved by animals living in this extreme environment.


Asunto(s)
Frío , Ecosistema , Homeostasis/fisiología , Metales Pesados/farmacocinética , Contaminantes Químicos del Agua/farmacocinética , Animales , Femenino , Glutatión/metabolismo , Hígado/enzimología , Metalotioneína/metabolismo , Oxidorreductasas/metabolismo , Perciformes , Especificidad de la Especie , Distribución Tisular
15.
Toxicol In Vitro ; 22(4): 980-7, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18356017

RESUMEN

In the present study, the interactions between zinc (Zn) and copper (Cu) or iron (Fe) have been examined. Rat hepatoma cell line H4-II-E-C3, fibroblast cell line mutant MT-/-, and wild-type MT+/+ cells treated with ZnSO4 or CuSO4 or FeSO4 or CuSO4+ZnSO4 or ZnSO4+FeSO4 for different times have been employed to study the effect of metallothionein (MT), glutathione (GSH) and metal (Cu, Fe and Zn) accumulation during cellular adaptation to supraphysiological metal concentrations. To investigate the different biological functions in the processes of metal homeostasis and detoxification, the levels of both MT-1 and MT-2 mRNAs have been evaluated. The three cell lines responded differently to metal treatments suggesting that the uptake and storage of these metals are affected by the specific cellular model and MT presence. In particular, Zn treatment significantly decreased Fe accumulation (p<0.05), whereas MT induced by Zn increased intracellular Cu content (p<0.05). Moreover, in H4-II-E-C3 cells administration of metals resulted in a rapid and transient induction of MT (p<0.05) and in GSH accumulation (p<0.05) suggesting synergistic interactions in which both appear essential for a protective regulatory function against the redox activity of metals. Taken together these results demonstrate that Zn affects the cellular levels of Cu and Fe by competition with the same ligand sites and/or by coordinate regulation of MT and GSH content.


Asunto(s)
Sulfato de Cobre/farmacología , Compuestos Ferrosos/farmacología , Metalotioneína/efectos de los fármacos , Sulfato de Zinc/farmacología , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Interacciones Farmacológicas , Sinergismo Farmacológico , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Homeostasis , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metalotioneína/metabolismo , Ratones , Ratones Noqueados , Oxidación-Reducción/efectos de los fármacos , Isoformas de Proteínas/efectos de los fármacos , Isoformas de Proteínas/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Virus 40 de los Simios
16.
Scand J Gastroenterol ; 42(12): 1495-500, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17994470

RESUMEN

OBJECTIVE: The physiology of iron metabolism in Wilson's disease is largely unknown, and there is a paucity of data on the real presence and progression of iron accumulation. The purpose of this study was to assess the iron metabolism parameters, including hepatic iron concentration, in follow-up liver biopsies and serum, and urinary pro-hepcidin. MATERIAL AND METHODS: Twenty-three Wilson's disease patients undergoing long-term treatment were enrolled in the study. RESULTS: Hepatic iron content was significantly increased in penicillamine-treated patients compared with zinc-treated patients. Serum and urinary pro-hepcidin concentrations were significantly higher in Wilson's disease patients than in healthy volunteers, despite a normal biochemical pattern of iron metabolism. CONCLUSIONS: Long-term penicillamine treatment seems to be responsible for a more marked iron accumulation in the liver. This observation may justify a revision of long-term Wilson's disease treatment modalities with penicillamine. The finding that serum and urinary pro-hepcidin is significantly increased in Wilson's disease patients compared with healthy volunteers suggests a role for hepcidin in iron metabolism in Wilson's disease, but this needs to be confirmed by a study of hepatic hepcidin expression in these patients.


Asunto(s)
Quelantes/uso terapéutico , Degeneración Hepatolenticular/tratamiento farmacológico , Hierro/metabolismo , Penicilamina/uso terapéutico , Sulfato de Zinc/uso terapéutico , Adolescente , Adulto , Biopsia , Femenino , Degeneración Hepatolenticular/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Resultado del Tratamiento
17.
Comp Biochem Physiol C Toxicol Pharmacol ; 146(4): 443-59, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17716951

RESUMEN

Copper, zinc and iron are essential metals for different physiological functions, even though their excess can lead to biological damage. This review provides a background of toxicity related to copper, iron and zinc excess, biological mechanisms of their homeostasis and their respective roles in the apoptotic process. The antioxidant action of metallothionein has been highlighted by summarizing the most important findings that confirm the role of zinc in cellular protection in relation to metallothionein expression and apoptotic processes. In particular, we show that a complex and efficient antioxidant system, the induction of metallothionein and the direct action of zinc have protective roles against oxidative damage and the resulting apoptosis induced by metals with redox proprieties. In addition, to emphasize the protective effects of Zn and Zn-MT in Cu and Fe-mediated oxidative stress-dependent apoptosis, some aspects of apoptotic cell death are shown. The most widely used cytochemical techniques also have been examined in order to critically evaluate the available data from a methodological point of view. The observations on the role of Zn and MT could potentially develop new applications for this metal and MT in biomedical research.


Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Metalotioneína/biosíntesis , Estrés Oxidativo/efectos de los fármacos , Zinc/farmacología , Animales , Línea Celular , Cobre/toxicidad , Histocitoquímica/métodos , Homeostasis , Humanos , Hierro/toxicidad , Oxidación-Reducción , Oxidorreductasas/metabolismo
18.
Mar Pollut Bull ; 54(7): 1020-30, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17367822

RESUMEN

The aim of the present work was to determine the activities of selected antioxidant enzymes (SOD, Se-GPX, CAT) in two species of bivalves, Scapharca inaequivalvis and Tapes philippinarum, from two sites of the lagoon of Venice that are characterized by different pO(2) (Marghera and Chioggia). The specimens were collected at four times during a 1-year period. In the two species studied, enzyme activities were found to be present in both digestive glands and gills, but with some species-specific differences that may also represent a different adaptation to seasonal variations. The presence of high SOD activities in the gills of both species may be related to their physiological role in respiration. Scapharca inaequivalvis is less sensitive than T. philippinarum to environmental changes, perhaps due to the presence of hemoglobins in this species. Moreover, in the digestive gland of T. philippinarum we found a significant negative correlation between the activities of SOD and GPX that may indicate the presence of oxidative stress. Some correlations between temperature/dissolved oxygen and antioxidant enzyme activity were present in specimens sampled in Marghera. Only GPX adequately responded to changes in dissolved oxygen and temperature, while the decrease in the activity of SOD and CAT in winter may be directly responsible for an enhanced susceptibility of mussels to oxidative stress during this period. We can conclude that the observed differences between Chioggia and Marghera are due to different concentrations of dissolved oxygen. Marghera is an appropriate location to study seasonal variations in water temperature. In fact, in this site, the differences between hot and cold months are quite evident.


Asunto(s)
Antioxidantes/metabolismo , Bivalvos/efectos de los fármacos , Sistema Digestivo/efectos de los fármacos , Branquias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxígeno/metabolismo , Scapharca/efectos de los fármacos , Animales , Antioxidantes/toxicidad , Bivalvos/metabolismo , Ciudades , Sistema Digestivo/metabolismo , Monitoreo del Ambiente , Activación Enzimática , Geografía , Branquias/metabolismo , Italia , Estrés Oxidativo/fisiología , Oxígeno/química , Scapharca/metabolismo , Estaciones del Año , Agua de Mar , Especificidad de la Especie , Temperatura , Factores de Tiempo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad
19.
J Clin Gastroenterol ; 40(10): 936-41, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17063115

RESUMEN

AIMS: To report on the diagnostic features, management, and clinical outcome after different treatments of Wilson's disease patients followed over a mean period of 15 years. PATIENTS: Thirty-five patients with Wilson's disease referred to the University of Padova's Department of Gastroenterology for diagnosis or treatment were observed for a mean 15 years. The diagnosis was based on clinical symptoms, laboratory tests (ceruloplasmin, urinary, and hepatic copper concentrations), and uptake of the radiostable isotope Cu into the plasma protein pool. Hepatic Cu content was measured by regular follow-up biopsies. Neurologic outcome after therapy was assessed using a newly developed scoring system. RESULTS: Twenty-three (65.7%) patients presented with liver disease; 12 (34.3%) had mixed neurologic and hepatic involvement. All patients had been initially treated with either penicillamine (23) or zinc sulfate (12). The neurologic symptoms became worse or remained stationary in 75% of those treated with penicillamine, whereas zinc treatment improved these symptoms in 90% of treated cases. Both treatments were effective in improving the hepatic symptoms. No differences in hepatic Cu content emerged between follow-up biopsies in either treatment group. Six patients (26%) had to abandon the penicillamine treatment due to side effects. In all, 4 patients underwent liver transplantation, which was successful in 3, with a mean survival after transplantation of 4.6 years; the fourth, who had a severe neurologic impairment, died of central pontine myelinolysis. CONCLUSIONS: Penicillamine and zinc can effectively treat Wilson's disease, though the side effects of penicillamine may be severe enough to prompt its suspension. Liver transplantation remains the treatment of choice for end-stage liver disease.


Asunto(s)
Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/terapia , Adolescente , Adulto , Alanina Transaminasa/sangre , Alanina Transaminasa/efectos de los fármacos , Biomarcadores/sangre , Biomarcadores/orina , Ceruloplasmina/efectos de los fármacos , Ceruloplasmina/metabolismo , Quelantes/administración & dosificación , Quelantes/efectos adversos , Niño , Preescolar , Cobre/orina , Femenino , Estudios de Seguimiento , Degeneración Hepatolenticular/metabolismo , Humanos , Isótopos/orina , Italia/epidemiología , Trasplante de Hígado , Imagen por Resonancia Magnética , Masculino , Penicilamina/administración & dosificación , Penicilamina/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tomografía Computarizada por Rayos X , Oligoelementos/uso terapéutico , Resultado del Tratamiento , Zinc/uso terapéutico
20.
Biochim Biophys Acta ; 1763(3): 305-12, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16563532

RESUMEN

It has been shown in various systems that zinc is able to antagonize the catalytic properties of the redox-active transition metals iron and copper, although the process is still unclear. Probably, the protective effect of Zn against oxidative stress is mainly due to the induction of a scavenger metal binding protein such as metallothionein (MT), rather than a direct action. To support this hypothesis, in this study, the effects of Zn, Cu, Fe, Zn + Cu and Zn + Fe treatments were investigated in a fibroblast cell line corresponding to an SV40-transformed MT-1/-2 mutant (MT-/-), and in wild type (MT+/+), by valuing metal concentrations and apoptotic and/or necrotic processes. We also investigated the synthesis of MT and the levels of both MT-1 and MT-2 mRNAs. In MT+/+ cells, co-treatment with Zn + Fe caused a decrease in Fe content compared to treatment with Fe alone. After Zn and Zn + Cu exposure the expression of MT-1 and MT-2 isoforms increased with a concomitant increase in MT synthesis. Annexin V-FITC and propidium iodide staining revealed necrotic or apoptotic cells in terminal stages, especially after Fe treatments. Immunofluorescent staining with an anti-ssDNA Mab and annexin detected a lower signal in co-treated cells compared to the single treatments in both cell lines. The intensity and quantity of fluorescence resulting from anti-ssDNA and Annexin V staining of MT null cells was higher compared to wild type cells. These results suggest that Zn alone does not completely exert an anti-oxidant effect against Cu and Fe toxicity, but that induction of MT is necessary.


Asunto(s)
Apoptosis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Metalotioneína/deficiencia , Metalotioneína/metabolismo , Necrosis , Zinc/farmacología , Animales , Línea Celular , Células Cultivadas , Cobre/farmacología , Fibroblastos/citología , Hierro/farmacología , Metalotioneína/genética , Ratones , Ratones Noqueados , Isoformas de Proteínas/deficiencia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
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