Papers by Maria Ana Santos
Translational Psychiatry, 2021
Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a foo... more Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate v...
BackgroundGenetics plays a major role in Alzheimer’s Disease (AD). To date, 40 genes associated w... more BackgroundGenetics plays a major role in Alzheimer’s Disease (AD). To date, 40 genes associated with AD have been identified, although most remain undiscovered. Clinical, neuropathological and genetic variability might impact genetic discoveries and complicate dissection of the biological pathways underlying AD.MethodsGR@ACE is a genome-wide study of dementia and its clinical endophenotypes that encompasses 4,120 cases and 3,289 controls from Spain. GR@ACE phenotypes were defined according to AD’s clinical certainty and the presence of vascular co-morbidity. To explore whether clinical endophenotypes reflect variation in underlying biological pathways, we first assessed the impact of known AD loci across endophenotypes to generate three loci categories. Next, we incorporated gene co-expression data and conducted pathway analysis on each category. To assess the impact of heterogeneity in the GWAS findings, the GR@ACE series were meta-analyzed with: 1) genotype-level data from dbGaP (...
Alzheimer's Research & Therapy, 2018
Background: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's dis... more Background: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aβ) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aβ species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. Methods: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18 F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aβ40 and Aβ42 peptides. The association between Aβ40 and Aβ42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aβ levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aβ plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis.
Marine Pollution Bulletin, 2010
In this study, the DNA integrity of golden grey mullet (Liza aurata) collected in differently con... more In this study, the DNA integrity of golden grey mullet (Liza aurata) collected in differently contaminated sites of a coastal lagoon, Ria de Aveiro (Portugal), was assessed, over the period of 1 year, using the DNA alkaline unwinding assay, in four different tissues (gill, kidney, liver and blood) and compared to a reference site. The four tissues displayed different DNA integrity basal levels, clearly affected by seasonal factors. Gill and kidney were, respectively, the most and least sensitive tissues. All sites demonstrated the capacity to interfere with DNA integrity. The sites displaying the highest and lowest DNA damage capability were, respectively, Barra (subject to naval traffic) and Vagos (contaminated with polycyclic aromatic hydrocarbons). In terms of seasonal variability, autumn seems to be the more critical season (more DNA damage) unlike summer when no DNA damage was found in any tissue. Data recommend the continued monitoring of this aquatic system.
Environment International, 2001
Anguilla anguilla L. ethoxyresorufin-O-deethylase (EROD) elevation by 2.7 microM beta-naphthoflav... more Anguilla anguilla L. ethoxyresorufin-O-deethylase (EROD) elevation by 2.7 microM beta-naphthoflavone (BNF) 3 days water exposure, or 4 mg/kg ip exposure, was studied in four different organs--liver, kidney, gills, and intestine. The results demonstrated a significant increase in liver EROD activity for the two previous conditions, whereas kidney EROD activity only increased during the intraperitoneal exposure. A. anguilla was also exposed during 8, 16, and 24 h to water contaminated with 2.7 microM BNF or benzo[a]pyrene (BaP) at 20 degrees C and 25 degrees C. Both compounds significantly increased liver EROD activity from 8 up to 24 h. There was no significant difference in liver EROD activity elevation by both compounds, either at 20 degrees C or 25 degrees C. Liver EROD activity was demonstrated to be one of the first warning systems concerning the presence of polycyclic aromatic hydrocarbons (PAHs) in water. A. anguilla 3 h exposure to diesel oil water-soluble fraction (DWSF) significantly increased plasma cortisol and significantly decreased plasma lactate. A prolonged exposure beyond 3 h, i.e. 4 h, 2, 3, 4, and 6 days to the previous conditions demonstrated a significant liver EROD activity elevation from Day 2 up to 6, and a significant increase in erythrocytic nuclear abnormalities (ENA) at Day 6.
Environment International, 2002
The effects of a polycyclic aromatic hydrocarbon (PAH) such as naphthalene (NAP)—an environmental... more The effects of a polycyclic aromatic hydrocarbon (PAH) such as naphthalene (NAP)—an environmental contaminant—and β-naphthoflavone (BNF)—a model substance (PAH-like compound)—were investigated in European eel (Anguilla anguilla L.) over 3-, 6-, and 9-day exposure (0.1–2.7 μM). Both xenobiotics revealed to be strong biotransformation (phase I) inducers. After 3-day exposure, liver ethoxyresorufin O-deethylase (EROD) activity was significantly increased by all NAP and
Ecotoxicology and Environmental Safety, 2004
The in vitro effects of chromium (Cr(VI)), copper (Cu2+), iron (Fe2+), mercury (Hg2+), and zinc (... more The in vitro effects of chromium (Cr(VI)), copper (Cu2+), iron (Fe2+), mercury (Hg2+), and zinc (Zn2+) were assessed on liver microsomal ethoxyresorufin O-deethylase (EROD) activity from a sea bass (Dicentrarchus labrax L.) preexposed under laboratory conditions to 2.7 microM beta-naphthoflavone. The reduced glutathione (GSH) protection potential against heavy metal effects was also studied. The heavy metal concentration ranges used for this study were as follows: 10 pM-5 mM Cr(VI), 10 pM-100 microM Cu2+, 10 pM-1 mM Fe2+, 10 pM-10 microM Hg2+, and 10 pM-100 microM Zn2+. Liver microsomal EROD activity was significantly inhibited after in vitro exposure to Cr(VI) (500 microM), Cu2+ (1 microM), Fe2+ (100 microM), Hg2+ (100 pM), and Zn2+ (10 microM). Heavy metals inhibitory effect on liver EROD activity was ordered as follows: Hg2+ &amp;amp;amp;amp;gt; Cu2+ &amp;amp;amp;amp;gt; Zn2+ &amp;amp;amp;amp;gt; Fe2+ &amp;amp;amp;amp;gt; Cr(VI). Protective effects against Hg2+ (1 and 10 microM), Cu2+ (1, 10, and 100 microM), and Zn2+ (10, 50, and 100 microM) were observed in the presence of 0.5 mM GSH by a decrease in liver microsomal EROD activity inhibition. However, 0.5 mM GSH did not protect liver microsomal EROD activity from Cr(VI), and Fe2+-induced inhibition. The effect of metal mixtures (Cu(2+) + Zn(2+), Zn(2+) + Fe(2+), Zn(2+) + Cr(VI), and Cr(VI) + Fe(2+)) (100 microM) on liver microsomal EROD activity was also assessed, revealing a synergistic interaction.
Ecotoxicology and Environmental Safety, 2003
The effect of naphthalene on phagocytes and associated abnormal cellular activities was studied i... more The effect of naphthalene on phagocytes and associated abnormal cellular activities was studied in Anguilla anguilla L. Fish were exposed to sublethal concentrations (0.1, 0.3, 0.9, 2.7 microM) of naphthalene for 8, 16, 24, 48, and 72 h. Gill, head kidney, and peritoneum phagocyte respiratory burst activity (RBA) was measured by nitroblue tetrazolium reduction assay, whereas lipid peroxidation in fish gill, kidney, and liver was measured by thiobarbituric acid reaction substance. A significant increase (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05-P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in total cell count (TCC) of phagocytes (TCCPH) isolated from gill, head kidney, and peritoneum was observed after 8 h of naphthalene exposure and persisting at 16 h exposure. However, long-term exposures (24, 48, and 72 h) induced a significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05-P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) decrease in TCC at all the concentration levels. Naphthalene exposure caused a significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05-P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) RBA induction after 8 and 16 h in gill, head kidney, and peritoneal phagocytes, which consequently resulted in a significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01 and P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) peroxidative tissue damage increase measured as lipid peroxidation (LPO) in gill, kidney, and liver at the same time intervals. Considering TCCPH, RBA, and LPO, the most affected tissues were gill and kidney after 8 and 16 h exposure to all naphthalene concentrations. RBA was significantly decreased after 24, 48, and 72 h of exposure (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05-P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas peroxidative damage increased significantly (P…
Environmental Pollution, 2012
This study aimed to investigate the role of non-enzymatic antioxidants on adaptive skills over ti... more This study aimed to investigate the role of non-enzymatic antioxidants on adaptive skills over time in the bivalve Scrobicularia plana environmentally exposed to mercury. Inter-age (2 D , 3 D , 4 D , 5 D year old) and organ-specific (gills, digestive gland) approaches were applied in bivalves collected from moderately and highly contaminated sites at Ria de Aveiro (Portugal). S. plana's adaptive skills were dependent on the contamination extent; under moderate contamination scenario, the intervention of the different antioxidants took place harmoniously, evidencing an adjustment capacity increasing with the age. Under higher contamination degree, S. plana failed to cope with mercury threat, showing an age-dependent deterioration of the defense abilities. In organ-specific approach, the differences were particularly evident for thiol-compounds, since only gills displayed the potential to respond to moderate levels by increasing non-protein thiols and total glutathione. Under high contamination degree, both organs were unable to increase thiol-compounds, which were compensated by the ascorbic acid elevation.
Medical & Biological Engineering, 1976
Conclusions A pen-counter system has been described which was found to be very useful for counti... more Conclusions A pen-counter system has been described which was found to be very useful for counting the number of muscle cells in the cross-section of narrow slips of the intercostal muscles. This system speeded up very drastically the whole counting procedure and made possible an extensive survey of the fibre densities in the intercostal muscles of dogs. It should also prove to be a convenient instrumental approach in all areas in which large numbers of small objects have to be counted.
Ecotoxicology and Environmental Safety, 1990
Lb?iversity oi'A veiro, 3800 .Iveiro. Portugal Recei ved b4av 16. 1Y89 Yellow eels (.4nguiNa arzg... more Lb?iversity oi'A veiro, 3800 .Iveiro. Portugal Recei ved b4av 16. 1Y89 Yellow eels (.4nguiNa arzgztilkz L.) with an average weight of 60 g were used in this experiment. The fish were caught in June/July at the Aveiro Lagoon on the Portuguese West Coast, transported to the Department of Biology. Aveiro University, and kept in aerated aquaria for 1 week before the experiment started. The eels were then exposed for I and 3 weeks to 75 and 50% of the kraft pulp mill effluent. The eels exposed to the kraft pulp mill effluent developed an increase in red blood cell number per cubic millimeter and several biochemical changes, such as an increase in plasma lactate and sodium and a decrease in plasma pyruvate and potassium. Histological examination of the experimental eels exposed to the 50% kraft pulp mill effluent revealed deep alteration of the tissue structure. such as disruption of the skin and edematous hypertrophy of covering epithelial'cells in secondary gill lamellae. The kidney had damage of the renal tubules. The liver developed necrosis supported by a significant decrease in GOT and GPT activity. The spleen had an increase in blood content as well as in pigment centers. Previous results indicated the kraft pulp mill effluent causes tissue damage and consequent metabolic changes in the eel .4qgui//a angui//a L. I&: 1990 Academic Press, IK.
Chemosphere, 2004
Juvenile sea bass, Dicentrarchus labrax L., were exposed during 2, 4, 8, and 24 h to 0.9 microM b... more Juvenile sea bass, Dicentrarchus labrax L., were exposed during 2, 4, 8, and 24 h to 0.9 microM beta-naphthoflavone (BNF), 131 nM 17 beta-estradiol (E(2)), 4.05 microM 4-nonylphenol (NP), as well as to BNF combined either to E(2) or NP (maintaining the previous concentrations). Liver cytochrome P450 content (P450), ethoxyresorufin-O-deethylase (EROD), and glutathione S-transferase (GST) activities were measured in order to evaluate biotransformation responses. Genotoxicity was assessed as erythrocytic nuclear abnormalities (ENA) frequency. The effects on endocrine function were evaluated as plasma cortisol and glucose. Cortisol was not affected by xeno/estrogens tested, either in single exposure or mixed with BNF. Nevertheless, the intermediary metabolism was affected since glucose concentration increased after 4 h exposure to E(2), and after all BNF+NP exposure lengths. Moreover, a synergism between BNF and NP was thoroughly demonstrated, whereas a sporadic antagonistic interaction was found at 4 h BNF + E(2) exposure. Liver EROD and GST activities were not significantly altered by single E(2) or NP exposure. However, both compounds were able to induce EROD activity in the presence of BNF. NP single exposure was able to significantly increase liver P450 content, while its mixture with BNF displayed an antagonistic interference. Considering the xeno/estrogens single exposures, only NP induced an ENA increase; however, both mixtures (BNF + E(2) and BNF + NP) displayed genotoxic effects. Fish responses to mixtures of xenobiotics are complex and the type of interaction (synergism/potentiation or antagonism) in a particular mixture can vary with the evaluated biological response.
Chemosphere, 2007
This study represents a first approach to short-term effects of phenanthrene (Phe) in fish. The t... more This study represents a first approach to short-term effects of phenanthrene (Phe) in fish. The teleost Liza aurata was exposed to 0.1-2.7 lM Phe during 16 h. CYP1A induction was assessed as liver ethoxyresorufin-O-deethylase (EROD) activity. Genotoxicity was evaluated in gill and liver as DNA integrity (by alkaline unwinding), whereas in blood the erythrocytic nuclear abnormalities (ENA) frequency was determined. Stress responses were determined as cortisol, glucose and lactate plasma levels. Liver EROD activity was significantly increased by Phe 0.3-2.7 lM. Phe genotoxicity in gill was not found, whereas liver DNA integrity significantly decreased after exposure to Phe 0.1 and 0.9 lM demonstrating its genotoxicity which did not correlate with liver CYP1A induction. Phe genotoxicity in blood was demonstrated by a significant ENA increase from 0.1 up to 2.7 lM. In terms of stress responses, plasma cortisol was significantly increased by Phe 0.3-2.7 lM, though plasma glucose was only significantly increased by Phe 0.9 and 2.7 lM. The Phe observed effects on L. aurata detected at different levels demonstrate a physiological unbalance and a probable ecological risk to ichthyofauna.
Chemosphere, 2006
The effect of bleached kraft pulp mill effluent (BKPME) persistent compounds on phagocyte activit... more The effect of bleached kraft pulp mill effluent (BKPME) persistent compounds on phagocyte activities and its organspecific influence in gill, kidney and liver was studied in European eel (Anguilla anguilla L.). Eels were caged and plunged at 3 different sites-50 m (site 1), 100 m (site 2) and 2000 m (site 3) away from the end of the closed BKPME discharging channel for 8 and 48 h. Gill, head kidney and peritoneum phagocytes oxidative burst activity (OBA) was measured by the nitroblue tetrazolium reduction assay whereas lipid peroxidation (LPO) in eel gill, kidney and liver was measured by thiobarbituric acid reaction. A significant gill OBA induction was found at 8 h on site 2, and on sites 1, 2 and 3 at 48 h exposure. However, in head kidney and peritoneal exudate phagocytes, OBA induction was significant only at sites 2 and 3 after 48 h exposure. In those particular sites, a significant increase in gill, kidney and liver LPO was measured that is assumed to result from OBA induction. Considering OBA and LPO, gill is the most affected tissue compared to kidney and liver. Gill vulnerability towards peroxidative damage was demonstrated at 8 h on site 2 and at 48 h on sites 1, 2 and 3, whereas in kidney was observed at sites 2 and 3 only at 48 h. Liver LPO increased at site 2 only after 48 h exposure. Our results demonstrate that the OBA activation pattern in gill and kidney is associated with the induced peroxidative damage extent in those organ, together with water pollution the exposure route, resulting from previous BKPME effluent sediment contamination which may affect the activation pattern of circulating fish phagocytes.
Ecotoxicology, 2009
Despite the importance of fish kidney in several functions (immune, metabolism and excretion of x... more Despite the importance of fish kidney in several functions (immune, metabolism and excretion of xenobiotics) its use in coastal water biomonitoring focusing on protection and damage is scarce. Five critical sites in Ria de Aveiro (Portugal; Barra--BAR, Gafanha--GAF, Rio Novo do Principe--RIO; Laranjo--LAR and Vagos--VAG) were assessed in comparison to a reference site (Torreira--TOR), focusing on Liza aurata kidney antioxidant defences versus damage responses. Non protein thiols were higher at RIO (near a former bleached kraft pulp mill effluent) and total glutathione at RIO, LAR (mercury contaminated) and VAG (polycyclic aromatic hydrocarbons contaminated). Catalase and glutathione S-transferase activities were higher at RIO and LAR whereas no differences were found in glutathione peroxidase activity. However, glutathione reductase was higher at BAR (subject to naval traffic), GAF (harbour water area), RIO and LAR. No peroxidative damage was observed despite the decreased DNA integrity at RIO and VAG. The integrated biomarker response index ranked impacted sites as: LAR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;RIO&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;BAR&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;GAF&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;VAG&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;TOR.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2006
Fish in the aquatic environment can be subjected to a multipollution state and the occurrence of ... more Fish in the aquatic environment can be subjected to a multipollution state and the occurrence of sequential exposures is an important aspect of eco-toxicological research. In this context, a preceding exposure can affect a toxic response to a subsequent exposure. Therefore, the current study was based on sequential exposures, viz. to a PAH-like compound (beta-naphthoflavone, BNF) followed by a heavy metal (chromium, Cr), focusing on the assessment of oxidative stress responses and their role in induction of genotoxicity. Oxidative stress responses in gill and kidney were investigated in European eel (Anguilla anguilla L.), and measured as lipid peroxidation (LPO), glutathione peroxidase (GPX), catalase (CAT) and glutathione S-transferase (GST) activity, and reduced glutathione (GSH) concentration, whereas genotoxicity was measured as DNA strand breakage. Fish were exposed for 24 h to two Cr concentrations (100 microM, 1 mM), with or without pre-exposure to BNF (2.7 microM, 24 h). In gill, a GSH decrease was observed along with loss of DNA integrity at all exposure conditions except at the lowest Cr concentration, showing a crucial role of GSH over genotoxicity. Moreover, sporadic induction of antioxidant enzymes was not effective in the protection against genotoxicity. However, a different mechanism seems to occur in kidney, since the loss of DNA integrity detected for all exposed groups was not accompanied by alterations in antioxidant levels. With regards to peroxidative damage, both organs showed an LPO increase after sequential exposure to BNF and 100 microM Cr. However, no association between LPO induction and antioxidant responses could be established, showing that LPO is not predictable solely on the basis of antioxidant depletion. The interference of BNF pre-exposure with the response of organs to Cr showed a marked dependence on the Cr concentration. Gill showed synergistic effects on LPO and GPX increase, as well as on CAT and GSH decrease for the lowest Cr concentration. However, for the highest concentration an additive effect on decrease of DNA integrity and an antagonistic effect on the increase of GPX were observed. In kidney, synergistic effects were evident on LPO increase and GSH decrease for the lowest Cr concentration, as well as on CAT and GST decrease for the highest concentration. In contrast, an antagonistic action was observed on DNA integrity loss for both Cr concentrations. The current results are relevant in assessing the interactions of PAHs and metals and contribute to a better knowledge about oxidative stress and mechanisms of genotoxicity in fish.
Environmental Toxicology, 2005
Anguilla anguilla L. (European eel) was exposed for 24 h to chromium (Cr-100 M and 1 mM) or coppe... more Anguilla anguilla L. (European eel) was exposed for 24 h to chromium (Cr-100 M and 1 mM) or copper (Cu-1 and 2.5 M), with or without a 24-h preexposure to -naphthoflavone (BNF-2.7 M), a polycyclic aromatic hydrocarbon (PAH)-like compound, simulating sequential exposure to PAHs and heavy metals. Plasma cortisol, thyroid-stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) were determined in order to assess the effects on endocrine function. Plasma glucose and lactate also were measured. The frequency of erythrocytic nuclear abnormalities (ENA) was scored as a genotoxicity indicator. Plasma T4 decreased in eels when exposed to Cr only. The interference of BNF preexposure on Cr effects was observed as a significant plasma glucose increase. Single exposures to Cu elevated plasma cortisol and glucose (2.5 M), as well as plasma lactate (1 M), whereas a T4 decrease was found for both concentrations. BNF preexposure prevented plasma cortisol and lactate increases; however, a greater T4 decrease was observed in eels exposed to 2.5 M Cu. Moreover, this pretreatment was crucial for genotoxicity expression because only BNFϩ2.5 M Cu-exposed fish exhibited significant ENA induction. In general, plasma T4 was the most affected hormone, as it responded to all Cr and Cu exposure conditions.
Environment International, 2006
The effects of 17beta-estradiol (E(2)) on fish became a matter of concern, since significant leve... more The effects of 17beta-estradiol (E(2)) on fish became a matter of concern, since significant levels of this hormone were detected in the aquatic environment released mainly by domestic sewage treatment plants. In this perspective, the current study was focused on E(2) effects upon biotransformation, stress and genotoxic responses of juvenile Dicentrarchus labrax L. (sea bass). Fish were exposed to E(2) during 10 days in two different ways: water diluted (200 ng/L or 2,000 ng/L) and i.p. injected (0.5 mg/kg or 5 mg/kg). A battery of biological responses was evaluated: liver ethoxyresorufin-O-deethylase (EROD) and alanine transaminase (ALT) activities, liver somatic index (LSI), plasma cortisol, glucose and lactate concentrations, as well as erythrocytic nuclear abnormalities (ENA). All the exposure conditions induced endocrine disruption, measured as plasma cortisol decrease, and genotoxicity, measured as ENA increase. Thus, no differences were detected either between different exposure routes or tested concentrations. Concerning liver EROD and ALT activities, as well as plasma glucose and lactate concentrations no differences were found between treated and control groups. LSI was the only parameter to respond differently in the two exposure routes, as only E(2) water diluted induced a significant increase in this hepatic indicator.
![Research paper thumbnail of Anguilla anguilla L. Biochemical and Genotoxic Responses to Benzo[a]pyrene](https://attachments.academia-assets.com/92580259/thumbnails/1.jpg)
Ecotoxicology and Environmental Safety, 2002
and 216 h to 0 (control), 0.3, 0.9, and 2.7 M benzo[a]pyrene (BaP). The biotransformation induced... more and 216 h to 0 (control), 0.3, 0.9, and 2.7 M benzo[a]pyrene (BaP). The biotransformation induced by BaP was measured as liver ethoxyresoru5n O-deethylase (EROD) activity and cytochrome P450 content, and compared with the genotoxic e4ects, such as erythrocytic nuclear abnormalities (ENA), and blood and liver DNA strand breaks. The liver exhibited a highly signi5cant EROD activity increase from 2 up to 216 h exposure to 0.9 and 2.7 M BaP, whereas 0.3 M BaP exposure induced a signi5cant liver EROD increase from 2 up to 144 h. Liver cytochrome P-450 content was signi5cantly increased at 8 h to 2.7 M BaP exposure. Liver DNA integrity was decreased at 16 h, from 8 up to 144 h and 8 up to 72 h exposure to 0.3, 0.9, and 2.7 M BaP, respectively. A signi5cant decrease in blood DNA integrity was observed at 48, 72, 144 h, from 8 up to 72, and from 6 up to 72 h exposure to 0.3, 0.9, and 2.7 M BaP, respectively. The A. anguilla L. genotoxic response to BaP, measured as ENA induction, was signi5cantly increased at 144 h exposure to 0.3 M BaP. The intermediate BaP concentration tested (0.9 M) induced a signi5cant three fold ENA increase at 48 and 72 h exposure compared to their controls. The highest BaP concentration (2.7 M) induced a signi5cant increase in ENA frequency at 72, 144 and 216 h exposure.
Ecotoxicology and Environmental Safety, 2008
Gill and kidney DNA integrity (alkaline unwinding assay) was assessed in Anguilla anguilla expose... more Gill and kidney DNA integrity (alkaline unwinding assay) was assessed in Anguilla anguilla exposed for 24-h to copper (Cu: 1 or 2.5 μM), with or without 24-h pre-exposure to a polycyclic aromatic hydrocarbon (PAH)-like compound--β-naphthoflavone (BNF: 2.7 μM). Gill showed DNA integrity loss in all the exposure conditions, reflecting a dual mode of BNF-Cu interaction depending on the metal concentration. Thus, antagonistic or additive effects were observed for BNF+Cu 1 μM or BNF+Cu 2.5 μM, respectively. Kidney showed decreased DNA integrity for single exposures (BNF, Cu 1 μM), whereas sequential exposures displayed higher DNA integrity than BNF alone, revealing a Cu antagonistic effect at both the concentrations. The results also demonstrated that (i) both organs are receptive for Cu inhibitory role against BNF genotoxicity; (ii) kidney is more resistant to Cu individual exposures; and (iii) under multi-pollution conditions genotoxicity cannot be predicted on the basis of individual chemicals responses.
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Papers by Maria Ana Santos