Biomedical subjects

Cinta Porte

Publications and source records attributed to Cinta Porte.

At least 19 recordsLinked to original sources

PubMed2007

Sex steroids and potential mechanisms of non-genomic endocrine disruption in invertebrates.

The review reports on the presence and metabolism of sex steroids in several invertebrate species and provides detailed information on possible mechanisms of endocrine disruption other than the interaction with nuclear receptors. The presence of most vertebrate sex steroids in invertebrate tissues has been demonstrated by liquid or gas chromatography coupled to mass spectrometry. In addition, enzymatic pathways involved in the steroidogenic pathway have been described in at least some invertebrate phyla. Some endocrine disruptors induce alterations in these metabolic pathways and might lead to changes in steroid levels. Growing evidence suggests that estradiol can act through non-genomic pathways in molluscs, and that xenobiotics can as well interfere in these signalling cascades. In spite of these recent advances, most question marks on the action and function of sex steroids in invertebrates remain to be answered.

Animals↗

PubMed2006

Comparing the response of biochemical indicators (biomarkers) and biological indices to diagnose the ecological impact of an oil spillage in a Mediterranean river (NE Catalunya, Spain).

Three biomarkers of hydrocarbon exposure, liver 7-ethoxyresourfin-O-deethylase activity (EROD), fluorescent hydrocarbon compounds (FACs) in bilis, and the liver antioxidant enzyme catalase (CAT) were examined in the autochthonous fish species Barbus meridionalis collected in the river Fluvià (NE Catalunya, Spain) after an oil spillage. Four different locations were sampled, including the impacted site, upstream and downstream sites and a reference site. Biomarker responses were compared with diatom and macroinvertebrate community assemblage metrics (Specific Pollution Sensitivity index - IPS, and Iberian Biological Monitoring Working Party - IBMWP, respectively). Chemical analyses denoted that polycyclic aromatic hydrocarbon levels in sediment were much higher at the impacted site than in downstream reaches. Four fold increase of EROD activity together with increased levels of biliary FACs in barbs collected at the spilled site indicated exposure of inhabiting fish to the oil. Additionally, CAT activity was significantly depressed (four fold) when compared to other stations, thus suggesting that fish collected from the impacted sites could be more susceptible to suffer oxidative stress. Biological indices (particularly that of the diatom community IPS) showed slight significant effects between control and impacted sites, indicating that more tolerant taxa were favoured because of the oil spillage. These results support the need to include biochemical responses measured in local species in monitoring programmes aimed to diagnose specific pollution effects in stressed river ecosystems.

Animals↗

PubMed2006

The interference of pharmaceuticals with endogenous and xenobiotic metabolizing enzymes in carp liver: an in-vitro study.

The interactions of fibrate (clofibrate, fenofibrate, bezafibrate, gemfibrozil), antiinflammatory (ibuprofen, diclofenac, naproxen, ketoprofen), and anti-depressive (fluoxetine,fluvoxamine, paroxetine) drugs with CYP catalyzed pathways (CYP1A, CYP3A-, CYP2K-, and CYP2M-like) and Phase II activities (UDP-glucuronosyltransferases and sulfotransferases), involved in both xenobiotic and endogenous metabolism in fish, were investigated in-vitro by incubating carp liver subcellular fractions in the presence of the substrate and the selected drug. Anti-depressive drugs were strong inhibitors of CYP1A (92-94% inhibition), CYP3A-like (69-80% inhibition), and CYP2K-like (36-69% inhibition) catalyzed activities, while antiinflammatory drugs were potent CYP2M-like inhibitors (32-74% inhibition). Among the lipid regulators, gemfibrozil strongly inhibited CYP2M-catalyzed activity (91% inhibition) and other CYP isoforms (CYP1A and CYP3A-like). Additionally, glucuronidation of naphthol and testosterone were targeted by antiinflammatory drugs, and to a lesser extent, by fibrate drugs (48-78% inhibition). No significant alteration on sulfotransferase activities was observed, apart from a minor inhibitory effect of clofibrate, gemfibrozil, and fluoxetine on the sulfation of estradiol. Overall, gemfibrozil, diclofenac, and the three anti-depressive drugs appear to be the pharmaceuticals with the highest potential to interfere with fish metabolic systems.

Animals↗

PubMed2006

Triphenyltin alters androgen metabolism in the sea urchin Paracentrotus lividus.

Androgen metabolism (androstenedione and testosterone) has been assessed in the digestive tube and gonads of the echinoderm Paracentrotus lividus exposed to different concentrations of the biocide triphenyltin (TPT) in a semi-static water regime for 4 weeks. Key enzymatic activities involved in both synthesis and metabolism of androgens, namely 17beta-hydroxysteroid dehydrogenases (17beta-HSDs), 3beta-HSDs, 5alpha-reductases, P450-aromatase, palmitoyl-CoA:testosterone acyltransferases (ATAT) and testosterone sulfotransferases (SULT), were investigated in digestive tube and/or gonads of control and TPT-exposed specimens in an attempt to see whether androgen metabolism was altered by exposure. In agreement with previous data for vertebrates, exposure to TPT led to a concentration dependent decrease of P450-aromatase that was statistically significant at the highest TPT concentration tested (225ng/L). Additionally, increased metabolism of testosterone to form dihydrotestosterone (DHT) and 5alpha-androstane-3beta,17beta-diol was observed, suggesting increased 5alpha-reductase activity in the gonads of TPT-exposed individuals. Interestingly, exposure to TPT induced testosterone conjugating activities in organisms exposed to medium (SULT) and high (ATAT and SULT) TPT concentrations. Despite the changes of androgen metabolizing enzymes, testosterone levels in gonads remained rather stable. In contrast, an increase in testosterone and a concomitant decrease in estradiol were observed in the coelomic fluid of TPT-exposed organisms. Overall, the data indicate the ability of TPT to modulate androgen metabolism and circulating steroid levels in P. lividus and suggest the existence of regulatory mechanisms to maintain stable endogenous levels of testosterone in gonads. This study also contributes to a better knowledge of echinoderm endocrinology.

Androstenedione↗

PubMed2006

Chemical residues and biochemical responses in wild and cultured European sea bass (Dicentrarchus labrax L.).

Cultured and wild sea bass (Dicentrarchus labrax) from the Arade Estuary were sampled in summer and winter and the degree of exposure to metals and polycyclic aromatic hydrocarbons (PAHs) assessed, together with some biochemical responses against those and other pollutants. The highest levels of copper (up to 997 microg g-1 dry weight) and cadmium (up to 4.22 microg g-1 dry weight) were detected in the liver and kidney of cultured specimens, whereas the highest exposure to PAHs was observed in wild fish. Significant alterations in some biochemical markers were detected and associated to pollutant exposure. Thus, metallothionein concentrations were higher in the tissues of cultured fish and positively correlated with metal residues. The activity 7-ethoxyresorufin O-deethylase ranged from 28 pmol/min/mg protein in cultured fish to 83 pmol/min/mg protein in wild fish collected near a marina area. Cultured fish and wild fish from the marina area had depressed acetylcholinesterase in muscle tissue and a parasitic infection in the gonads. The obtained results support the usefulness of the combined use of chemical and biochemical markers to assess the impact of anthropogenic pollutants in both wild and cultured fish.

Acetylcholinesterase↗

PubMed2006

Sulfotransferase activities towards xenobiotics and estradiol in two marine fish species (Mullus barbatus and Lepidorhombus boscii): characterization and inhibition by endocrine disrupters.

We have characterized hepatic phenol sulfotransferase (SULT) activities in two benthic fish species, Mullus barbatus and Lepidorhombus boscii, using p-nitrophenol, dopamine, 17beta-estradiol, 4-nonylphenol, and 1-naphthol as substrates. High affinity sulfation of 17beta-estradiol was observed in both species (Km=28-75 nM), suggesting the presence of a specific estrogen sulfotransferase that catalyzes the formation of estradiol-3 sulfate. Among the tested compounds, 1-naphthol was the most effective substrate for sulfation, with Vmax/Km ratios several hundred-fold higher than the other substrates examined. Both species sulfated the tested compounds, but only M. barbatus was able to sulfate dopamine. We also tested the inhibitory effects of common marine pollutants with estrogenic (4-nonylphenol) and androgenic (tributyltin, triphenyltin) properties on p-nitrophenol and 17beta-estradiol SULT activities. 4-Nonylphenol and triphenyltin inhibited sulfation of both substrates at micromolar concentrations in both species. However, tributyltin was only effective against SULTs from L. boscii, again at micromolar concentrations. The data indicate that M. barbatus and L. boscii are able to sulfate a range of xenobiotics and endogenous compounds, and inhibition of these activities by environmental pollutants may contribute to the known toxic effects of these compounds.

Animals↗

PubMed2006

Sexual dimorphism in esterified steroid levels in the gastropod Marisa cornuarietis: the effect of xenoandrogenic compounds.

Molluscs can conjugate a variety of steroids to form fatty acid esters. In this work, the freshwater ramshorn snail Marisa cornuarietis was used to investigate sex differences in endogenous levels of esterified steroids. Testosterone and estradiol were mainly found in the esterified form in the digestive gland/gonad complex of M. cornuarietis, and males had higher levels of esterified steroids than females (4-10-fold). Additionally, the ability of several xenobiotics, namely tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN) to interfere with the esterification of testosterone and estradiol was investigated. All three compounds induced imposex - appearance of male sexual characteristics in females. Exposure to TBT led to a decrease in both esterified testosterone (60-85%) and estradiol (16-53%) in females after 100 days exposure, but had no effect on males. Exposure to FEN and MT did not alter levels of esterified steroids in males or in females, although exposed females developed imposex after 150 days exposure. The decrease in esterified steroids by TBT could not be directly linked with a decrease in microsomal acyl-CoA:testosterone acyltransferase (ATAT) activity, which catalyzes the esterification of steroids. In fact, ATAT activity was marginally induced in organisms exposed to TBT for 50 days (1.3-fold), and significantly induced in males and females exposed to MT for 50 days (1.8- and 1.5-fold, respectively), whereas no effect on ATAT activity was observed after 150 days exposure.

Androgens↗

PubMed2006

Endocrine alteration in juvenile cod and turbot exposed to dispersed crude oil and alkylphenols.

Juvenile Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus) were exposed for 3 weeks in a continuous water flow to 0.5 ppm of dispersed North Sea crude oil, 0.5 ppm of dispersed North Sea crude oil spiked with 0.1 ppm of a mixture of alkylphenols (offshore oil production), and 30 ppb of nonylphenol (NP). As potential markers of endocrine alteration, key enzymatic activities involved in both synthesis (17beta-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism (liver UDP-glucuronosyltransferases (UGT) and sulfotransferases) of steroids were assessed together with circulating levels of testosterone and estradiol in plasma. NP-exposed turbot had lower ovarian P450 aromatase, lower levels of testosterone and estradiol in plasma, and lower glucuronidation rates of sex steroids than those from the control group. In contrast, higher liver UGT-testosterone, and a trend towards higher P450 aromatase was detected in oil-exposed specimens. Those exposed to the combination oil+alkylphenols had lower levels of estradiol in plasma than controls, and no significant effects on any the enzymatic activities tested was observed. All these alterations were more evident in turbot than in cod. In fact, apart from a higher glucuronidation rate of estradiol detected in the liver of NP-exposed cod, no significant differences were observed between control and exposed cod.

Animals↗

PubMed2006

Steroid levels and steroid metabolism in the mussel Mytilus edulis: the modulating effect of dispersed crude oil and alkylphenols.

Significant amounts of oil and alkylphenols are released into the sea by petroleum installations as a result of discharges of produced water. Some of these pollutants elicit estrogenic responses in fish, but their effects on the endocrine system of molluscs are largely unknown. In this study, mussels Mytilus edulis were exposed to North Sea oil (O) and the mixture of North Sea oil+alkylphenols (OAP), and the effects on tissue steroid levels and steroid metabolism (P450-aromatase and estradiol-sulfotransferase) were monitored. Levels of free testosterone and free estradiol were much higher in gonad tissue than in peripheral tissue, whereas esterified steroids (released after saponification) were of the same order of magnitude in both tissues. Levels of free steroids determined in gonads were not affected by exposure, but esterified steroids significantly increased in OAP exposed mussels (up to 2.4-fold). The sulfation of estradiol was investigated as a conjugation pathway, and increased activities were observed in digestive gland cytosol of both O and OAP exposure groups (up to 2.8-fold). Additionally, increased P450-aromatase activity was determined in OAP exposed mussels (up to three-fold, both in gonad and digestive gland), but not in the O group. Altogether, the results indicate that North Sea oil leads to increased sulfation of estradiol, and that in combination with alkylphenols, additional alterations are observed: increased P450-aromatase, and increased levels of esterified-steroids in gonads. Nonetheless, mussels are able to maintain gonad concentrations of free steroids unaltered, possibly via homeostatic mechanisms such as the conjugation with fatty acid or the formation of sulphate conjugates.

Analysis of Variance↗

PubMed2006

Steroid levels in crinoid echinoderms are altered by exposure to model endocrine disruptors.

Sexual steroids (testosterone and estradiol) were measured in the whole body of wild specimens of the crinoid Antedon mediterranea collected from the Tyrrhenian Sea (Italy). Testosterone levels (274-1,488 pg/g wet weight (w.w.)) were higher than those of estradiol (60-442 pg/g w.w.) and no significant differences between males and females were observed. No clear seasonal trend was either detected - individuals from February, June and October 2004 analyzed - apart from a peak of estradiol in males in autumn. Nonetheless, dramatic changes on tissue steroid levels were observed when individuals were exposed to model androgenic and anti-androgenic compounds for 2 and 4 weeks. The selected compounds were 17 alpha-methyltestosterone (17 alpha-MT), triphenyltin (TPT), fenarimol (FEN), cyproterone acetate (CPA), and p,p'-DDE. Endogenous testosterone levels were significantly increased after exposure to 17 alpha-MT, TPT and FEN, while different responses were observed for estradiol; 17 alpha-MT and FEN increased endogenous estradiol (up to seven-fold), and TPT lead to a significant decrease. Concerning the anti-androgenic compounds, CPA significantly reduced testosterone in a dose-dependent manner without altering estradiol levels, whereas specimens exposed to p,p'-DDE at a low dose (24 ng/L) for 4 weeks showed a four-fold increase in T levels. Overall, the data show the ability of the selected compounds to alter endogenous steroid concentrations in A. mediterranea, and suggest the existence in this echinoderm species of vertebrate-like mechanisms that can be affected by exposure to androgenic and anti-androgenic chemicals.

Androgen Antagonists↗

PubMed2006

COMPRENDO: Focus and approach.

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .

Androgens↗

PubMed2005

Effects of 17beta-estradiol exposure in the mussel Mytilus galloprovincialis: a possible regulating role for steroid acyltransferases.

Mussels (Mytilus galloaprovincialis) were exposed to different concentrations of estradiol (20, 200, and 2000 ng/L) in a semi-static regime (1-day dosing intervals) for up to 7 days in an attempt to see how mussels deal with exogenous estrogenic compounds. Whole tissue free-estradiol levels were only significantly elevated at the high exposure dose, whereas total-estradiol (free+esterified) sharply increased in a dose-dependent manner, from 2 ng/g in controls to 258 ng/g at the high exposure group. Neither free nor esterified testosterone levels showed significant differences between control and exposed organisms. The results suggest the existence of mechanisms that allow mussels to maintain their hormonal levels stable, with the exception of the high exposure dose, and the important role that fatty acid esterification, e.g. palmitoyl-CoA:estradiol acyltransferases, may play within those mechanisms. Additionally, the activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase, P450-aromatase, and estradiol-sulfotransferases were investigated in digestive gland microsomal and cytosolic fractions. All these activities were differently affected by estradiol exposure. Overall, the study contributes to the better knowledge of molluscan endocrinology, and defines new mechanisms of regulation of free steroid-levels in mussels.

Acyltransferases↗

PubMed2005

Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean.

Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17beta-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean.

Animals↗

PubMed2005

The combined use of chemical and biochemical markers to assess water quality along the Ebro River.

Carp (Cyprinus carpio) and barbel (Barbus graellsii) were collected from five sites along the Ebro River. The study was designed to assess levels of persistent organic pollutants and metals bioaccumulated by fish, and some biochemical responses (cytochrome P450 system, phase II activities, and metallothioneins) against those pollutants. The highest levels of PCBs and DDTs were detected in carp from industrialised areas, which also showed high levels of mercury and cadmium in the liver, and high levels of nonylphenol in bile. Significant alterations in some biochemical markers were observed and associated to combined exposure to pollutants. The activity 7-ethoxyresorufin O-deethylase ranged from 69 pmol/min/mg protein in carp from the reference site to 415 pmol/min/mg protein in those from polluted sites. Carp from the Ebro Delta, an agricultural area, had depressed acetylcholinesterase in muscle tissue. Metallothionein concentrations were positively correlated with copper residues, but no significant differences among sampling points were observed.

Animals↗

PubMed2005

Antioxidant enzyme activities and lipid peroxidation in the freshwater cladoceran Daphnia magna exposed to redox cycling compounds.

Contaminant-related changes in antioxidative processes in the freshwater crustacea Daphnia magna exposed to model redox cycling contaminant were assessed. Activities of key antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferases and levels of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) and lipofucsin pigment content were determined in D. magna juveniles after being exposed to sublethal levels of menadione, paraquat, endosulfan, cadmium and copper for 48 h. Results denoted different patterns of antioxidant enzyme responses, suggesting that different toxicants may induce different antioxidant/prooxidant responses depending on their ability to produce reactive oxygen species and antioxidant enzymes to detoxify them. Low responses of antioxidant enzyme activities for menadione and endosulfan, associated with increasing levels of lipid peroxidation and enhanced levels of antioxidant enzyme activities for paraquat, seemed to prevent lipid peroxidation, whereas high levels of both antioxidant enzyme activities and lipid peroxidation were found for copper. For cadmium, low antioxidant enzyme responses coupled with negligible increases in lipid peroxidation indicated low potential for cadmium to alter the antioxidant/prooxidant status in Daphnia. Among the studied enzymes, total glutathione peroxidase, catalase and glutathione S-transferase appeared to be the most responsive biomarkers of oxidative stress.

Animals↗

PubMed2005

Changes in antioxidant enzyme activities, fatty acid composition and lipid peroxidation in Daphnia magna during the aging process.

Age-related changes in the balance between endogenous pro-oxidative and antioxidative processes in the freshwater cladoceran Daphnia magna (Crustacea) were assessed. The activities of key antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase and levels of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) were determined in eight age classes, covering juvenile, young and senescent adults. Age-related changes in fatty acid composition were also measured to examine the contribution of polyunsaturated fatty acids (PUFA) in the peroxidation status of animals. Biochemical responses depicted in this study demonstrated that age-related decline in survival was accompanied by increasing oxidative stress and oxidative damage. Enhanced oxidative stress in aging D. magna was suggested by the significant increase in the formation of lipid peroxides, and a concomitant reduction of unsaturated fatty acids of 20 or more carbon atoms. Because aging was accompanied by selective loss of key antioxidant enzymes and small changes in the amount of PUFA, the breakdown of antioxidant defences might have directly contributed to oxidative stress, membrane lipid peroxide and a decline of survival. Indeed, the results reported here, indicate that age-related increases of lipid peroxides were at least partially due to the functional imbalance of enzymatic antioxidant defences.

Aging↗

PubMed2004

Effects of endocrine disrupters on sex steroid synthesis and metabolism pathways in fish.

The interactions of estrogenic (nonylphenol, dicofol, atrazine), androgenic (organotins, phthalates, fenarimol) and anti-androgenic compounds (vinclozolin, diuron, p,p'-DDE) with key enzymatic activities involved in both synthesis and metabolism of sex hormones was investigated. Carp testicular microsomes incubated in the presence of androstenedione and different xenobiotics evidenced higher sensitivity of 5alpha-reductase activity than 17beta-hydroxysteroid dehydrogenase activity towards those chemicals. Dicofol, organotins and phthalates were among the most effective inhibitors. In contrast, ovarian synthesis of maturation-inducing hormones (20alpha- and 20beta-hydroxysteroid dehydrogenase activities) were enhanced by nonylphenol, dicofol, fenarimol and p,p'-DDE. Metabolic clearance pathways of hormones were also affected. Fenarimol, nonylphenol and triphenyltin inhibited the glucuronidation of testosterone and estradiol at concentrations as low as 10, 50 and 100 microM, respectively. Triphenyltin, tributyltin and nonylphenol were also inhibitors of estradiol sulfation with IC(50) values of 17, 18 and 41 microM. Overall, the data indicates the interaction of selected chemicals with key enzymatic pathways involved in both synthesis and metabolism of sex hormones. This interference might be one of the underlying mechanisms for the reported hormonal disrupting properties of the tested compounds, and might finally affect physiological processes such as gamete growth and maturation.

Androstenedione↗

PubMed2004

First evidence of endocrine disruption in feral carp from the Ebro River.

Feral carps (Cyprinus carpio) were collected in spring 2001 from five sites along the lower course of Ebro River (Spain) with the aim of investigating the existence of endocrine-disrupting effects. Several findings (low gonadosomatic index (GSI), plasmatic vitellogenin (VTG), depressed levels of testosterone, and histological alterations in gonads) detected in male carps downstream of Zaragoza's sewage treatment plant (STP) strongly suggest that the concentration of sewage effluent in the area is a major causal factor leading to the detected estrogenic effects. Important alterations (viz. delayed maturation in females, indications of arrested spermatogenesis in males) were detected in carps from Flix, a heavily industrialized area. Low ovarian P-450 aromatase and reduced glucuronidation of testosterone and estradiol in males were observed in Zaragoza and Canal Imperial de Aragón-an agricultural area-which suggest decreased estrogen synthesis, and possibly, reduced sex hormone excretion in those organisms. These results were related to some in vitro assays aimed to assess the interference of model compounds (atrazin, vinclozolin, diuron, pp'-DDE, dicofol, triphenyltin, nonylphenol, and fenarimol) with the glucuronidation of testosterone and estradiol by liver microsomal fractions. The fungicide fenarimol (10-20 microM) and nonylphenol (50 microM) were found to significantly inhibit (20%) both activities at relatively low doses. Overall, this work provides the first evidence of the existence of significant alterations of the endocrine system of carps from the medium-low course of the Ebro River and demonstrates the ability of several chemicals to modulate the inactivation of endogenous steroids.

Animals↗