Biomedical subjects

M Oliveira

Publications and source records attributed to M Oliveira.

At least 19 recordsLinked to original sources

PubMed2026

Impact of BRCA2 pathogenic variants on outcomes to first-line CDK4/6 inhibitors plus endocrine therapy in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain. PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH). RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors. CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

Humans↗

PubMed2007

Programming effects of antenatal dexamethasone in the developing mesolimbic pathways.

Elevated glucocorticoids, during pregnancy, alter emotionality and increase propensity to drug abuse later in life, albeit through substrates and mechanisms are largely unknown. In this study, we examined whether antenatal glucocorticoid exposure induces enduring structural changes in the nucleus accumbens (NAcc), an important relay point in the reward limbic circuitry. To this end, rat dams were exposed to the synthetic glucocorticoid dexamethasone (DEX) on days 18 and 19 of gestation, and stereological tools were used to assess the total volume of, and neuronal numbers in, the NAcc, as well as the density of mesencephalic dopaminergic inputs from the ventral tegmental area (VTA) to the NAcc in their adult offspring. Further, we used measures of bromodeoxyuridine incorporation into NAcc cells to examine whether DEX-induced effects on cell proliferation represent another mechanism through which glucocorticoids alter the structure of mesolimbic pathways and might influence addictive behavior. Our studies show that exposure to DEX during late gestation results in significantly reduced volumes and cell numbers in the NAcc. The latter measure correlated strongly with a reduced rate of cell proliferation in DEX-exposed animals. Moreover, the treatment resulted in a decreased number of cells expressing tyrosine hydroxylase in the VTA and an impoverished dopaminergic innervation of the NAcc. These observations, which identify glucocorticoid-sensitive structures and neurochemical targets within the developing "reward pathway," pave way for future studies designed to understand how early life events can predispose individuals for developing drug dependence in adolescent and adult life.

Animals↗

PubMed2006

PpRT1: the first complete gypsy-like retrotransposon isolated in Pinus pinaster.

We have isolated and characterized a complete retrotransposon sequence, named PpRT1, from the genome of Pinus pinaster. PpRT1 is 5,966 bp long and is closely related to IFG7 gypsy retrotransposon from Pinus radiata. The long terminal repeats (LTRs) have 333 bp each and show a 5.4% sequence divergence between them. In addition to the characteristic polypurine tract (PPT) and the primer binding site (PBS), PpRT1 carries internal regions with homology to retroviral genes gag and pol. The pol region contains sequence motifs related to the enzymes protease, reverse transcriptase, RNAseH and integrase in the same typical order known for Ty3/gypsy-like retrotransposons. PpRT1 was extended from an EST database sequence indicating that its transcription is occurring in pine tissues. Southern blot analyses indicate however, that PpRT1 is present in a unique or a low number of copies in the P. pinaster genome. The differences in nucleotide sequence found between PpRT1 and IFG7 may explain the strikingly different copy number in the two pine species genome. Based on the homologies observed when comparing LTR region among different gypsy elements we propose that the highly conserved LTR regions may be useful to amplify other retrotransposon sequences of the same or close retrotransposon family.

Amino Acid Sequence↗

PubMed2006

Ultrastructure and germination of Vitis vinifera cv. Loureiro pollen.

The cultivar Loureiro of Vitis vinifera is one of the most economically important, recommended in almost the totality of the Região Demarcada dos Vinhos Verdes. In vineyards, the grape productivity of this cultivar is normal while in others it is extremely low. The aim of this work was to study the morphology and germination of Vitis vinifera cv. Loureiro pollen with high and low productivity. The pollen grain was examined under light, transmission and scanning electron microscopy. Typically V. vinifera pollen present three furrows but in the cultivar Loureiro we found tricolporated and acolporated (without furrows or pores) pollen grains. Both pollen types present generative and vegetative cells with the usual aspect and a dense cytoplasm rich in organelles. In the acolporated pollen a continuous exine layer and an irregular intine layer were observed. Differences were found in the starch accumulation, since only in tricolporated pollen abundant plastids filled with numerous starch granules were observed. To determine the causes of the low productivity of this cultivar we tested pollen viability by the fluorochromatic reaction and pollen germinability by in vitro assays. We observed that the acolporated pollen grain is viable, but no germination was recorded.

Cell Survival↗

PubMed2006

Cytochrome P4501A, genotoxic and stress responses in golden grey mullet (Liza aurata) following short-term exposure to phenanthrene.

This study represents a first approach to short-term effects of phenanthrene (Phe) in fish. The teleost Liza aurata was exposed to 0.1-2.7microM Phe during 16h. 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 0.3-2.7microM. Phe genotoxicity in gill was not found, whereas liver DNA integrity significantly decreased after exposure to Phe 0.1 and 0.9microM 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 2.7microM. In terms of stress responses, plasma cortisol was significantly increased by Phe 0.3-2.7microM, though plasma glucose was only significantly increased by Phe 0.9 and 2.7microM. The Phe observed effects on L. aurata detected at different levels demonstrate a physiological unbalance and a probable ecological risk to ichthyofauna.

Animals↗

PubMed2006

Biofilm-forming ability profiling of Staphylococcus aureus and Staphylococcus epidermidis mastitis isolates.

Biofilm-forming ability has been increasingly recognized as an important virulence factor in Staphylococci, facilitating their persistence in the host, evading its defences and allowing bacterial survival at high antimicrobial concentrations. Staphylococcus aureus remains a major pathogen of chronic mastitis, but in the last years Staphylococcus epidermidis has emerged as a relevant mastitis pathogen. The present work aimed at the evaluation of the biofilm-forming ability of Staphylococci field isolates from bovine subclinical mastitis and at the development of a fluorescent in situ hybridisation (FISH) protocol that would allow the direct observation of biofilm formation in milk samples. The analysis of phenotypic expression in Congo Red Agar (CRA) and by FISH, showed that 37.5% of the S. aureus isolates produced biofilm, while by optical density measurement only 18.75% isolates revealed this phenotype. The results showed a fair agreement according to the kappa coefficient test (kappa = 0.259). Regarding S. epidermidis mastitis isolates, 37.5% revealed the ability to produce biofilm, but only four isolates were positive by all methods. This agreement was moderate (kappa = 0.467). The application of FISH to artificially contaminated milk samples allowed the direct observation of biofilm production by 37.5% isolates, showing total agreement with the CRA results. This method better mimics the in vivo conditions, especially in terms of the presence of calcium and iron, which in high concentrations, respectively, are known to inhibit or induce biofilm production.

Animals↗

PubMed2006

Oxidative stress and genotoxic effects in gill and kidney of Anguilla anguilla L. exposed to chromium with or without pre-exposure to beta-naphthoflavone.

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.

Anguilla↗

PubMed2006

Oxidative stress, liver biotransformation and genotoxic effects induced by copper in Anguilla anguilla L.--the influence of pre-exposure to beta-naphthoflavone.

Fish are exposed in the aquatic ecosystems to different classes of pollutants. Polycyclic aromatic hydrocarbons (PAHs) and heavy metals represent two important classes of aquatic contaminants. Thus, one lot of European eels (Anguilla anguilla L.) was pre-exposed during 24 h to 2.7 microM beta-naphthoflavone (BNF; a PAH-like compound), and subsequently exposed during 24 h to 0, 1 and 2.5 microM copper (Cu). Additionally, another lot not pre-exposed to BNF was exposed to the same Cu concentrations. BNF pre-exposure promoted a significant increase in liver ethoxyresorufin O-deethylase (EROD) activity, but did not change the other responses investigated in eels. On the other hand, both Cu concentrations did not modify the liver EROD activity either in eels pre-exposed to BNF or not. Liver total cytochrome P450 was increased in eels exposed to Cu 2.5 microM, being significantly only in eels not pre-exposed to BNF. Free sulfhydryl group content was decreased by 1 and 2.5 microM in eels pre-exposed to BNF or not pre-exposed, being significant at 2.5 microM Cu in eels not pre-exposed compared to its control. Liver total glutathione (TG), reduced glutathione (GSH) and GSH/oxidized glutathione (GSSG) levels were slightly decreased by 1 and 2.5 microM Cu in eels pre-exposed to BNF, whereas a slight tendency to increase was observed in eels not pre-exposed. Thus, liver TG and GSH significantly decreased in 2.5 microM Cu BNF pre-exposed eels compared to eels not pre-exposed to BNF. Liver glutathione reductase and catalase activities were significantly inhibited by 1 and 2.5 microM Cu in eels pre-exposed to BNF, concomitantly with a slight liver glutathione peroxidase tendency to decrease. Lipid peroxidation was significantly increased by 1 microM Cu in eels either pre-exposed or not pre-exposed to BNF. Liver H(2)O(2) was significantly increased by 1 microM Cu in eels pre-exposed to BNF. Liver DNA integrity was significantly decreased by 1 and 2.5 microM Cu in eels pre-exposed to BNF. The oxidative stress and genotoxic effects induced by Cu in eels pre-exposed to BNF revealed that the metal effects are potentiated by previous exposure to BNF.

Anguilla↗

PubMed2006

Construction and characterization of a Lactococcus lactis strain deficient in intracellular ClpP and extracellular HtrA proteases.

A Lactococcus lactis strain deficient in both its major proteases, intracellular (ClpP) and extracellular (HtrA), was constructed and characterized. This strain, hereafter called clpP-htrA, could be obtained only by conjugation between a clpP donor strain and an htrA recipient strain in the NZ9000 context, allowing heterologous gene expression under the control of the NICE (nisin-controlled expression) system. The clpP-htrA double mutant showed both higher stress tolerance (e.g. high temperature and ethanol resistance) and higher viability than single clpP or htrA mutant strains. In addition, the secretion rate of two heterologous proteins (staphylococcal nuclease Nuc and Nuc-E7) was also higher in clpP-htrA than in the wild-type strain. This strain should be a useful host for high-level production and quality of stable heterologous proteins.

Conjugation, Genetic↗

PubMed2006

Development of an inhibition ELISA test for the detection of non-capsid polyprotein 3ABC in viral suspensions destined for inactivated foot-and-mouth disease vaccines.

The use during the last decade of immuno-enzymatic tests based on the detection of antibodies to the non-capsid proteins (NCPs) of foot-and-mouth disease virus (FMDV) to assess viral circulation, irrespective of vaccination, supported the incorporation into the OIE code of the 'free from FMDV with vaccination' category and opened the way to a 'vaccination to live' policy. Eradication programmes in South America include systematic vaccination accompanied by large serosurveys through NCP antibody testing to ensure the absence of residual viral activity. For correct interpretation of serosurveys, a major prerequisite is that vaccines made of semi-purified preparations of inactivated virions do not contain levels of NCPs, which upon proper presentation conditions, could induce an antibody response under the conditions for field immunization. This work describes the development of an inhibition ELISA to detect NCP polyprotein 3ABC in viral suspensions destined for vaccine production as an in-process control during vaccine manufacture. Antibody responses against NCP 3ABC in vaccinated and revaccinated cattle, induced by vaccines with different purification processes and formulations, are discussed.

Animals↗

PubMed2005

Age-related qualitative shift in emotional behaviour: paradoxical findings after re-exposure of rats in the elevated-plus maze.

Several variables, including age, are known to influence anxiety. Previous exposure to the elevated-plus maze (EPM) is known to modify emotional behaviour as retesting in the EPM at a standard age of 3 months increases open-arm avoidance and attenuates the effects of anxiolytic drugs. This study analysed whether similar results are obtained when older animals are subjected to these experimental paradigms. Overall, increasing age was associated with more signs of anxiety. Additionally, we observed a paradoxical behaviour pattern in aged-subjects that were re-exposed to the EPM, with mid-aged and old rats failing to display open arm avoidance (OAA) in the second trial; this qualitative shift in emotional behaviour was not associated with decreased locomotion. An examination of how age influences responsiveness to anxiolytic drugs, with or without previous maze experience, was also conducted. Midazolam (0.5 and 1 mg/kg) proved anxiolytic in maize-naive young animals; in marked contrast, in older animals midazolam at 1 mg/kg resulted in sedation but not anxiolyis. One trial tolerance to midazolam was evident in animals of both ages that were subjected to a second EPM trial; the latter phenomenon was apparently accentuated in older animals as they do not show open arm avoidance upon re-exposure to the EPM. These data suggest that the age-associated 'resistance' to anxiolytic drugs might be related to a qualitative shift in emotional behaviour.

Aging↗

PubMed2005

Biotransformation and genotoxic biomarkers in mullet species (Liza sp.) from a contaminated coastal lagoon (Ria de Aveiro, Portugal).

The aim of the present study was to assess liver ethoxyresorufin-O-deethylase (EROD) activity and erythrocytic nuclear abnormalities (ENA) frequency in three mullet species, as biotransformation and genotoxicity biomarkers, respectively, for monitoring aquatic ecosystems. Specimens of Liza aurata, Liza ramada and Liza saliens were caught bimonthly, between May 2000 and March 2001, at nine stations in the Ria de Aveiro (Portugal), a polluted coastal lagoon. The survey revealed two critical areas (Vagos and Carregal) where it was observed elevated EROD activity and ENA frequency, comparing to the reference sites. The results often reflect a contamination by a mixture of pollutants, from point and non-point sources. Nevertheless, the responses observed at Vagos are probably attributable to high polycyclic aromatic hydrocarbon (PAH) water levels measured at that station. All species were able to detect inter-site differences; however L. aurata seems to be the most appropriate bio-indicator due to its larger geographical distribution and abundance during the whole year. The adopted biomarkers, applied to mullet species, can be successfully employed for biomonitoring anthropogenic contamination in both Atlantic and Mediterranean European coastal waters.

Animals↗

PubMed2005

Use of RAPD markers for identifying Nelore bulls with early reproductive maturation onset.

Random amplified polymorphic DNA (RAPD) markers were used for identifying animals with early (precocious) or late (non-precocious) reproductive maturation onset. Animals (n=34) were phenotyped according to spermatozoa appearance in ejaculates (group A, 20 animals) or to the expected progeny difference (EPD) values for scrotal circumference (group B, 14 animals). The RAPD markers were initially detected by amplifying two pooled samples of equimolar amounts of DNA from the eight precocious 12 and non-precocious animals of group A. Only 38 out of 320 random primers used for screening group A pooled samples detected polymorphisms. These polymorphic primers generated 443 distinguishable and reproducible bands, from which 174 were polymorphic and 269, monomorphic. These polymorphic primers were then used in RAPD reactions to amplify individual DNA samples from animals belonging to both groups, A and B. The dendrograms generated from RAPD patterns allowed phenotypic class differentiation in both cases. Therefore, RAPD markers can be used as a tool for identifying genotypes favoring early sexual maturation in Nelore breeding programs.

Animals↗

PubMed2005

Oxidative stress and genotoxic responses to resin acids in Mediterranean mussels.

This study represents the first attempt to investigate the genotoxic effects and oxidative stress of resin acids in Mediterranean mussels (Mytilus galloprovincialis Lmk). Mussels were exposed to 2.7 microM abietic acid (AA) and dehydroabietic acid (DHAA) for 6, 12, 18, and 24h. Gill and hepatopancreas conjugation activity, antioxidant defense system, lipid peroxidation (LPO), and DNA damage were determined as reduced glutathione (GSH), glutathione S-transferase (GST) activity, glutathione peroxidase (GPx) activity, catalase (CAT) activity, LPO, and DNA strand breaks. AA caused significant GST inhibition in mussel gills at 12, 18, and 24h. Activity of the antioxidant enzymes, namely, GPx and CAT, was inhibited at 24 and 18 h, respectively, in mussel gills. A significant increase in gill LPO was observed at 24h. The DNA integrity of mussel hepatopancreas significantly decreased after 12 and 24 h exposure to AA. A significant increase in LPO was observed after 6h exposure to DHAA, in either mussel gills or hepatopancreas. DNA integrity was significantly decreased in mussel hepatopancreas after 12 and 24 h exposure to DHAA. AA induced oxidative damage and genotoxicity in mussels, because it promoted increases in LPO in gills and DNA strand breaks in hepatopancreas. DHAA promoted oxidative damage and genotoxicity in mussels, as significant increases were observed in LPO in gills and hepatopancreas and in DNA strand breaks in hepatopancreas.

Abietanes↗

PubMed2005

Endocrine and metabolic changes in Anguilla anguilla L. following exposure to beta-naphthoflavone--a microsomal enzyme inducer.

Anguilla anguilla L. were exposed during 24 and 48 h to 2.7 muM beta-naphthoflavone (BNF), a known microsomal enzyme inducer. The BNF effects on thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine (T4) and cortisol plasma levels were investigated. Alterations on plasma glucose and lactate levels were also measured as an indication of energy-mobilizing hormones alterations. BNF showed to be able to decrease significantly A. anguilla plasma T4 levels, whereas TSH, T3 and cortisol plasma remained constant. However, plasma glucose levels were significantly increased, demonstrating that intermediary metabolism has been affected. These results demonstrate that BNF a PAH-like compound alters the normal functioning of the hypothalamo-pituitary-thyroid (HPT) axis in A. anguilla.

Anguilla↗

PubMed2005

Adolescent and adult congenital heart disease assessed by real-time three-dimensional echocardiography: an initial experience.

Real-time three-dimensional (3D) echocardiography has enormous diagnostic potential, enabling acquisition of full-volume three-dimensional images in real time, which can be sliced in several planes and rotated in order to achieve a more accurate study of the target cardiac structures. It is particularly useful because it enables the heart to be visualized from multiple perspectives in the same way a surgeon would see it during an operation. We describe our echocardiographic laboratory's experience with real-time 3D ultrasound study of adolescent and adult congenital heart disease.

Adolescent↗

PubMed2004

Immunolocalisation of arabinogalactan proteins and pectins in Actinidia deliciosa pollen. Short communication.

The cell wall composition of germinating pollen grains of Actinidia deliciosa was studied by immunolocalization with monoclonal antibodies against arabinogalactan proteins (AGPs) and pectins. In ungerminated pollen, the JIM8 epitope (against a subset of AGPs) was located in the intine and in the cytoplasm, while the MAC207 epitope (against AGPs) was located only in the exine. After germination, the JIM8 and MAC 207 epitopes were located in the cytoplasm and in the pollen tube wall. The Yariv reagent that binds to AGPs was added to the germination medium inducing a reduction or inhibition in pollen germination. This indicates that AGPs are present in the growing pollen tube and play an important role in pollen germination. To identify the nature of the pectins found in pollen grains and tubes, four monoclonal antibodies were used. The JIM5 epitope (against unesterifled pectins) was located in the intine, more intensely in the pore region, and along the pollen tube wall, and the JIM7 epitope (against methylesterified pectins) was also observed in the cytoplasm. After germination, the JIM5 epitope was located in the pollen tube wall; although, the tube tip was not labelled. The JIM7 epitope was located in the entire pollen tube wall. LM5 (against galactans) showed a labelling pattern similar to that of JIM5 and the pattern of LM6 (against arabinans) was similar to that of JIM7. Pectins show different distribution patterns when the degree of esterification is considered. Pollen tube wall pectins are less esterified than those of the pollen tube tip. The association of AGPs with pectins in the cell wall of the pollen grain and the pollen tube may play an important role in the maintenance of cell shape during pollen growth and development.

Actinidia↗

PubMed2004

Glutathione protects heavy metal-induced inhibition of hepatic microsomal ethoxyresorufin O-deethylase activity in Dicentrarchus labrax L.

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+ > Cu2+ > Zn2+ > Fe2+ > 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.

Animals↗