Biomedical subjects

Marcelo Farina

Publications and source records attributed to Marcelo Farina.

At least 19 recordsLinked to original sources

PubMed2006

Differential susceptibility following beta-amyloid peptide-(1-40) administration in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive deficits and the glutathione system response.

Considerable evidence supports the role of oxidative stress in the pathogenesis of Alzheimer's disease (AD). Previous studies suggest that the central nervous system (CNS) administration of beta-amyloid peptide, the major constituent of senile plaque in AD, induces oxidative stress in rodents which may contribute to the learning and memory deficits verified in the beta-amyloid model of AD. In the present study, we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated beta-amyloid peptide-(1-40) (Abeta(1-40)) (400pmol/mouse) on spatial learning and memory performance, synaptic density and the glutathione (GSH)-dependent antioxidant status in adult male C57BL/6 and Swiss albino mice. Seven days after Abeta(1-40) administration, C57BL/6 and Swiss mice presented similar spatial learning and memory impairments, as evaluated in the water maze task, although these impairments were not found in Abeta(40-1)-treated mice. Moreover, a similar decline of synaptophysin levels was observed in the hippocampus (HC) and prefrontal cortex (PFC) of both Swiss and C57BL/6 mice treated with Abeta(1-40), which suggests synaptic loss. C57BL/6 mice presented lower levels of glutathione-related antioxidant defences (total glutathione (GSH-t) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activity) in the HC and PFC in comparison to Swiss mice. Despite the reduced basal GSH-dependent antioxidant defences observed in C57BL/6 mice, Abeta(1-40) administration induced significant alterations in the brain antioxidant parameters only in Swiss mice, decreasing GSH-t levels and increasing GPx and GR activity in the HC and PFC 24h after treatment. These results indicate strain differences in the susceptibility to Abeta(1-40)-induced changes in the GSH-dependent antioxidant defences in mice, which should be taken into account in further studies using the Abeta model of AD in mice. In addition, the present findings suggest that the spatial learning and memory deficits induced by beta-amyloid peptides in rodents may not be entirely related to glutathione-dependent antioxidant response.

Amyloid beta-Peptides↗

PubMed2006

Lactational exposure to inorganic mercury: evidence of neurotoxic effects.

This study examined the effects of inorganic mercury (mercuric chloride - HgCl2) exposure exclusively through maternal milk on biochemical parameters related to oxidative stress (glutathione and thiobarbituric acid reactive substances levels, glutathione peroxidase and glutathione reductase activities) in the cerebellum of weanling mice. These parameters were also evaluated in the cerebellum of mothers, which were subjected to intraperitoneal injections of HgCl2 (0, 0.5 and 1.5 mg/kg, once a day) during the lactational period. Considering the relationship between cerebellar function and motor activity, the presence of motor impairment was also evaluated in the offspring exposed to HgCl2 during lactation. After treatments (at weaning), pups lactationally exposed to inorganic mercury showed high levels of mercury in the cerebellar tissue, as well as significant impairment in motor performance in the rotarod task and decreased locomotor activity in the open field. Offspring and dams did not show changes in cerebellar glutathione levels or glutathione peroxidase activity. In pups, lactational exposure to inorganic mercury significantly increased cerebellar lipoperoxidation, as well as the activity of cerebellar glutathione reductase. However, these phenomena were not observed in dams. These results indicate that inorganic mercury exposure through maternal milk is capable of inducing biochemical changes in the cerebellum of weanling mice, as well as motor deficit and these phenomena appear to be related to the pro-oxidative properties of inorganic mercury.

Animals↗

PubMed2006

Antioxidant effect of diphenyl diselenide against sodium nitroprusside (SNP) induced lipid peroxidation in human platelets and erythrocyte membranes: an in vitro evaluation.

An in vitro evaluation on the antioxidant effect of diphenyl diselenide (PhSe)(2), an organochalcogenide, against sodium nitroprusside (SNP)-induced lipid peroxidation (LPO) was conduced. Human platelets and erythrocyte membranes (ghosts), as well as rat brain homogenates (S(1)), were pre-incubated with different concentrations of SNP (0-10 microM). All SNP concentrations tested significantly increased LPO in human platelets and S(1). Platelets were more sensitive to SNP-induced peroxidative damage when compared to S(1). SNP 10 microM decreased glutathione peroxidase (GPx) activity and did not affect glutathione reductase (GR) and catalase (CAT) activities in human platelets. However, ghosts were insensitive to SNP-induced LPO and no changes on GPx, GR and CAT activities were observed. Diphenyl diselenide significantly protected human platelets against SNP-induced LPO and recovered GPx inactivation. This effect was more evident at (PhSe)(2) concentrations above 2 microM. The presented results indicate that (PhSe)(2) exerts protective effects on SNP-induced oxidative damage in human blood components and in rat brain. These phenomena seem to be related to its thiol peroxidase-like activity and to a possible direct interaction with SNP and derivatives. Based on our results and on literature, diphenyl diselenide can be pointed as a promising antioxidant molecule.

Animals↗

PubMed2006

Postnatal methylmercury exposure induces hyperlocomotor activity and cerebellar oxidative stress in mice: dependence on the neurodevelopmental period.

During the early postnatal period the central nervous system (CNS) is extremely sensitive to external agents. The present study aims at the investigation of critical phases where methylmercury (MeHg) induces cerebellar toxicity during the suckling period in mice. Animals were treated with daily subcutaneous injections of MeHg (7 mg/kg of body weight) during four different periods (5 days each) at the early postnatal period: postnatal day (PND) 1-5, PND 6-10, PND 11-15, or PND 16-20. A control group was treated with daily subcutaneous injections of a 150 mM NaCl solution (10 ml/kg of body weight). Subjects exposed to MeHg at different postnatal periods were littermate. At PND 35, behavioral tests were performed to evaluate spontaneous locomotor activity in the open field and motor performance in the rotarod task. Biochemical parameters related to oxidative stress (levels of glutathione and thiobarbituric acid reactive substances, as well as glutathione peroxidase and glutathione reductase activity) were evaluated in cerebellum. Hyperlocomotor activity and high levels of cerebellar thiobarbituric acid reactive substances were observed in animals exposed to MeHg during the PND 11-15 or PND 16-20 periods. Cerebellar glutathione reductase activity decreased in MeHg-exposed animals. Cerebellar glutathione peroxidase activity was also decreased after MeHg exposure and the lowest enzymatic activity was found in animals exposed to MeHg during the later days of the suckling period. In addition, low levels of cerebellar glutathione were found in animals exposed to MeHg during the PND 16-20 period. The present results show that the postnatal exposure to MeHg during the second half of the suckling period causes hyperlocomotor activity in mice and point to this phase as a critical developmental stage where mouse cerebellum is a vulnerable target for the neurotoxic and pro-oxidative effects of MeHg.

Animals↗

PubMed2006

Lactational exposure to malathion inhibits brain acetylcholinesterase in mice.

The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound. Although some studies have reported neurotoxicity signs after the in utero exposure to OP pesticides, there is no evidence of the exclusive contribution of the lactational exposure to malathion as a possible cause of neurotoxicity in the offspring. In this study, we investigated the exclusive contribution of malathion exposure through maternal milk on the activity of acetylcholinesterase (AChE), as well as on biochemical parameters related to the oxidative stress (glutathione levels, lipid peroxidation and glutathione reductase and glutathione peroxidase activities) in the brain of suckling mice. The same parameters were also evaluated in the brains of the respective mothers, which where directly exposed to malathion during the lactational period (daily s.c. injections; doses of 20, 60 and 200mg/kg of body weight). Our results showed that the lactational exposure to malathion caused a high inhibitory effect of the brain AChE activity in the offspring, even when dams were exposed to the lowest malathion dose (20mg/kg). Brain AChE activity was also inhibited in mothers; however, only at the highest malathion dose (200mg/kg). No changes were observed in the biochemical parameters related to the oxidative stress for both dams and pups brains. The present study shows, for the first time, that the exposure of neonatal mice to malathion via lactation inhibits the activity of brain AChE in the offspring. These data, summed to the fact that OP pesticides are excreted in human milk, makes relevant the lactational exposure to these xenobiotics in terms of human health concerns.

Acetylcholinesterase↗

PubMed2006

Cerebellar thiol status and motor deficit after lactational exposure to methylmercury.

This study examined the exclusive contribution of methylmercury (MeHg) exposure through maternal milk on biochemical parameters related to the thiol status (glutathione (GSH) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activities) in the cerebellums of suckling mice. The same biochemical parameters were also evaluated in the cerebellums of mothers, which were submitted to a direct oral exposure to MeHg (10 mg/L in drinking water). With regard to the relationship between cerebellar function and motor activity, the presence of signs of motor impairment was also evaluated in the offspring exposed to MeHg during lactation. After the treatment (at weaning period), the pups lactationally exposed to MeHg showed increased levels of mercury in the cerebellum compared to pups in the control group and a significant impairment in the motor performance in the rotarod apparatus. In addition, these pups showed decreased levels of GSH in the cerebellum compared to pups in the control group. In dams, MeHg significantly increased the levels of cerebellar GSH and the activities of cerebellar GR. However, this was not observed in pups. This study indicates that (1) the exposure of lactating mice to MeHg causes significant impairments in motor performance in the offspring which may be related to a decrease in the cerebellar thiol status and (2) the increased GSH levels and GR activity, observed only in the cerebellums of MeHg-exposed dams, could represent compensatory pathophysiologic responses to the oxidative effects of MeHg toward endogenous GSH.

Animals↗

PubMed2006

Acetaldehyde does not inhibit glutathione peroxidase and glutathione reductase from mouse liver in vitro.

Acetaldehyde, the primary ethanol metabolite, has been implicated in the pathogenesis of alcoholic liver disease, but the mechanism involved is still under investigation. This study aims at the search for direct in vitro effects of different concentrations of acetaldehyde (30, 100 and 300microM) on the activities of glutathione reductase (GR), glutathione peroxidase (GPx) from liver supernatants, and the thiol-peroxidase activity of ebselen. They did not change after pre-incubation with acetaldehyde, which suggests that acetaldehyde does not have any direct effect. Nor were direct effects of acetaldehyde toward thiols, such as dithioerythritol and glutathione (GSH), observed either, even though GSH - measured as non-protein thiols from liver supernatants - were oxidized in the presence of acetaldehyde. In addition, acetaldehyde (up to 300microM) significantly oxidized GSH when incubated in the presence of commercially available gamma-glutamyltranspeptidase (GGT), but not in the presence of glutathione-S-transferase. The interaction between ebselen and GSH was also evaluated in an attempt to better understand the possible link between acetaldehyde and nucleophilic selenol groups. The formation and stability of ebselen intermediaries, produced in the chemical interaction between GSH and ebselen, were not affected by acetaldehyde either. Overall, the acetaldehyde oxidation of hepatic low-molecular thiols depends on mouse liver constituents and GGT is proposed as an important enzyme involved in this phenomenon. Thiol depletion, a phenomenon usually observed in the livers of alcoholic patients, can be related to GSH metabolism, and the involvement of GGT may reflect a molecular mechanism involved in thiol oxidation.

Acetaldehyde↗

PubMed2005

Effects of ethanol and diphenyl diselenide exposure on the activity of delta-aminolevulinate dehydratase from mouse liver and brain.

Ethanol toxicity is affected by both environmental and inherited features. Since oxidative stress is an important molecular mechanism for ethanol-induced cellular damage, the concomitant exposure to ethanol and pro-oxidative or antioxidant compounds can alter its toxicity. Here, we investigate the effects of exposure to ethanol and/or diphenyl diselenide, an organochalcogen with antioxidant properties, on parameters related to oxidative stress (thiobarbituric acid reactive species-TBARS-and delta-aminolevulinate dehydratase-delta-ALA-D activity) in mouse liver and brain. In addition, the in vitro effects of ethanol and acetaldehyde on the activity of delta-ALA-D from human erythrocytes were also investigated. Both ethanol and diphenyl diselenide decreased hepatic delta-ALA-D activity and DL-dithiothreitol (DTT) reactivated this enzyme only after ethanol-induced inhibition. Moreover, ethanol increased liver TBARS levels, independently of the presence of diphenyl diselenide treatment. Brain delta-ALA-D activity and TBARS levels were not changed by ethanol or diphenyl diselenide exposure. Under in vitro conditions, acetaldehyde was a more potent inhibitor of delta-ALA-D from human erythrocytes when compared to ethanol, demonstrating a dose-dependent effect. This study indicates that (1) hepatic delta-ALA-D is a molecular target for the damaging effect of ethanol under in vivo conditions; (2) diphenyl diselenide and ethanol seem to inhibit delta-ALA-D by different mechanisms; (3) acetaldehyde, a metabolite of ethanol, is probably the main molecule responsible for the inhibitory effects of the parent compound on delta-ALA-D.

Animals↗

PubMed2005

Mechanism of delta-aminolevulinate dehydratase inhibition by phenyl selenoacetylene involves its conversion to diphenyl diselenide.

The mechanism of delta-aminolevulinate dehydratase (delta-ALA-D) inhibition by phenyl selenoacetylene in vitro was investigated in this study. Phenyl selenoacetylene (40-400 microM) inhibition of delta-aminolevulinate dehydratase from rat liver (low speed supernatant fraction, S1 fraction) was partially prevented by incubation under argon atmosphere and completely prevented by dithiothreitol. After incubation with S1 fraction from rat liver or cysteine (40 mM), phenyl selenoacetylene was partially converted into diphenyl diselenide, which is a stronger inhibitor of delta-aminolevulinate dehydratase than phenyl selenoacetylene. Diphenyl diselenide increased the rate of oxidation of -SH groups, while phenyl selenoacetylene did not affect such oxidation. delta-Aminolevulinate dehydratase purified from bovine liver (Sigma) was less sensitive to phenyl selenoacetylene and diphenyl diselenide than the enzyme from S1 fraction. We propose that the lower sensitivity of purified enzyme to selenides could be related to the formation of selenols due to the presence of dithiothreitol (a reducing agent) in the incubation medium. In agreement, incubation of purified enzyme (Sigma) with diphenyl diselenide (2 microM) and sodium borohydride (a reducing agent) under argon atmosphere significantly increased enzyme activity. Results obtained suggest that delta-aminolevulinate dehydratase inhibition by phenyl selenoacetylene is dependent on its conversion into diphenyl diselenide that induces oxidation of essential -SH groups of delta-aminolevulinate dehydratase. We propose that oxygen could be important in the regeneration of diphenyl diselenide leading to a catalytic oxidation of the enzyme.

Acetylene↗

PubMed2005

Organic and inorganic forms of selenium inhibited differently fish (Rhamdia quelen) and rat (Rattus norvergicus albinus) delta-aminolevulinate dehydratase.

Selenium contamination in the aquatic environment can produce severe toxic effects to fish. The mammalian sulfhydryl-containing enzyme, delta-aminolevulinate dehydratase (delta-ALA-D), is inhibited after exposure to organic and inorganic forms of selenium. In the present study, the inhibitory effect of (PhSe)2, (BuSe)2, and Na2SeO3 on the activity of fish hepatic and gill delta-ALA-D was investigated and compared with the rat liver enzyme. Results indicated that delta-ALA-D activity varied considerably depending on the tissue, selenium form, and species considered. For fish (liver and gill), the IC50 values for delta-ALA-D inhibition by (PhSe)2, (BuSe)2, and Na2SeO3 were 274 and 76, 985 and 693, and 386 and 902 microM, respectively. For rat liver these values were 7, 10, and 5 microM, respectively. In contrast, fish and rat subcellular fractions similarly increased the oxidative effect of (PhSe)2 toward sulfhydryl groups from DTT. These catalytic properties of subcellular fractions from fish and rat liver were abolished by heat treatment. Taking into account that aquatic organisms can be in contact with higher concentrations of selenium for longer periods of time and accumulate more selenium than terrestrial animals, it is reasonable to suppose that fish delta-ALA-D can be a potential target for organic and inorganic selenium forms present in aquatic contaminated environments. From an ecotoxicological point of view, our results suggest a link between selenium-induced anemia signs in fish and the sensitivity of fish delta-ALA-D to selenium in natural habitats.

Animals↗

PubMed2005

Hemolytic effects of sodium selenite and mercuric chloride in human blood.

Many works have reported the interaction between selenium and mercury in the mammalian body and that chalcogen seems to have a protective effect against mercury toxicity. The aim of this study was to investigate the hemolytic effects of sodium selenite and/or mercuric chloride in human blood under in vitro conditions. For this, total venous blood from healthy subjects (males and females) was heparinized and incubated at 37 degrees C for 90 min with different concentrations of sodium selenite and/or mercuric chloride. The hemolytic effects of compounds were evaluated by measuring plasma hemoglobin concentration after centrifugation. In addition, 2-thiobarbituric acid reactive substances (TBARS) from plasma and erythrocytes, as well as erythrocyte nonprotein thiols (NPSH), were also evaluated in order to investigate molecular mechanisms related to selenite- or mercury-induced hemolysis. Mercuric chloride and sodium selenite, alone (400 microM), promoted a small in vitro hemolytic effect in human erythrocytes. However, when blood was exposed to both compounds (200 microM of each), there was an extremely high synergistic hemolytic effect. The exposure of blood to sodium selenite (400 microM), mercuric chloride (400 microM), and both compounds (200 microM each) did not alter erythrocyte TBARS levels. Sodium selenite presented a high oxidant effect toward erythrocyte NPSH; however, this effect was inhibited by mercuric chloride. The current results point to a synergistic hemolytic effect of sodium selenite and mercuric chloride in human blood, suggesting new understanding on the selenium-mercury antagonism. Moreover, this observed hemolysis seems to be not related to lipoperoxidation or thiol depletion.

Adult↗

PubMed2005

Protective effects of Polygala paniculata extract against methylmercury-induced neurotoxicity in mice.

We have examined the possible protective effects of Polygala paniculata extract against methylmercury (MeHg)-induced neurotoxicity in adult mice. MeHg was diluted in drinking water (40 mg L(-1), freely available) and the hydroalcoholic Polygala extract was diluted in a 150 mM NaCl solution and administered by gavage (100 mg kg(-1) b.w., twice a day). After a two-week treatment, MeHg exposure significantly inhibited glutathione peroxidase and increased glutathione reductase activity, while the levels of thiobarbituric acid reactive substances were increased in the cerebral cortex and cerebellum. These alterations were prevented by administration of Polygala extract, except for glutathione reductase activity, which remained elevated in the cerebral cortex. Behavioural interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control levels by Polygala extract co-administration. This study has shown, for the first time, the in-vivo protective effects of Polygala extract against MeHg-induced neurotoxicity. In addition, our findings encourage studies concerning the beneficial effects of P. paniculata on neurological conditions related to excitotoxicity and oxidative stress.

Animals↗

PubMed2004

Anticonvulsant effect of GMP depends on its conversion to guanosine.

Studies on the purinergic system normally deal with adenine-based purines, namely, adenine nucleotides and adenosine. However, a guanine-based purinergic system may also have important neuromodulatory roles. Guanine-based purines exert trophic effects on neural cells, protect brain slices in a model of hypoxia and stimulate glutamate uptake. In vivo, both guanosine 5'-monophosphate (GMP) and guanosine (GUO) protected against seizures. In this study, we investigated if the anticonvulsant effect of GMP is mediated by guanosine and if guanosine or GMP treatments were able to increase adenosine levels. Intraperitoneal (i.p.) treatments with 7.5 mg/kg GMP or guanosine prevented 50% of seizures by quinolinic acid (QA) and increased guanosine cerebrospinal fluid (CSF) levels around twofold and threefold, respectively; GMP and adenosine levels remained unchanged. Intracerebroventricular treatment with 960 nmol GMP prevented 80% of seizures and the 5'-nucleotidase inhibitor alpha-beta-methyleneadenosine 5'-diphosphate (AOPCP), when injected 3 min before, reduced this anticonvulsant effect to 30% protection as well as significantly decreased the conversion of GMP into guanosine measured in the CSF. This study shows that the previously reported effect of GMP as an anticonvulsant seems to be related to its ability to generate guanosine through the action of ecto-5'-nucleotidase.

Adenosine Diphosphate↗

PubMed2004

Methyl phenyl selenide causes heme biosynthesis impairment and its toxicity is not modified by dimethyl sulphoxide in vivo.

Organoselenium compounds can cause anemia in mice, possibly as a consequence of impairment of the heme biosynthesis pathway. Such compounds can inhibit the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (delta-ALA-D), which is involved in the heme biosynthetic pathway, leading to a decrease in the syntheses of hemoglobin, cytochromes and other heme-proteins. Methyl phenyl selenide (CH3SePh) has chemopreventive activity against cancer in rodents, raising the possibility of therapeutic use of this compound by humans. Treatment with methyl phenyl selenide (500 micromol/kg/day, 30 days) inhibited the delta-aminolevulinate dehydratase activity in adult male mice. Furthermore, the exposure to methyl phenyl selenide caused an increase in the liver/body weight ratio and a decrease in the hemoglobin content when compared to the control animals. The vehicle used (DMSO or corn oil) did not affect any of the analyzed parameters or the selenide effects towards these parameters. In summary, results presented here support that delta-aminolevulinate dehydratase is a potential target to CH3SePh, leading to an impairment of hemoglobin content, a heme biosynthetic endpoint.

Animals↗

PubMed2003

Ebselen protects against methylmercury-induced inhibition of glutamate uptake by cortical slices from adult mice.

Methylmercury (MeHg) is a highly neurotoxic compound and the inhibition of glutamate uptake by astrocytes has been pointed as an important mechanism involved in MeHg-induced glutamate excitotoxicity. We examined the effect of oral exposure to MeHg (10 and 40 mg/l in drinking water) on glutamate uptake by brain cortical slices of adult mice. Moreover, the possible protective role of ebselen (20 mg/kg, subcutaneously) against MeHg effect was also examined. In addition, it was measured the glutathione peroxidase and catalase activities in mice brain. Our results demonstrated, for the first time, that in vivo exposure to MeHg causes a dose-dependent decrease in glutamate uptake and that ebselen, which did not affect the uptake per se, reverted this effect. MeHg decreased glutathione peroxidase activity and increased catalase activity, effects which were also prevented by ebselen. These results may indirectly indicate that: (i) the in vivo inhibitory effect of MeHg on glutamate uptake could be probably related to overproduction of H(2)O(2); (ii) the protective effect of ebselen on MeHg-induced inhibition of glutamate uptake could be related to its ability to detoxify H(2)O(2).

Animals↗

PubMed2003

Profile of nonprotein thiols, lipid peroxidation and delta-aminolevulinate dehydratase activity in mouse kidney and liver in response to acute exposure to mercuric chloride and sodium selenite.

The effects of mercury (Hg(2+)) and selenite (Se(4+)) on delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, 2-thiobarbituric acid reactive substances (TBARS) and nonprotein sulfhydryl content (NPSH) in mouse kidney and liver were investigated. Male mice were given a single i.p. injection of Hg(2+) and/or Se(4+) (25 micromol/kg) and were killed at 6, 12, 24 and 48 h after treatment. Hg(2+) inhibited renal delta-ALA-D at 6 and 12 h after treatment. Se(4+) abolished the inhibitory effect of mercury on renal delta-ALA-D at 12 h after treatment. Renal and hepatic NPSH content decreased after Hg(2+) exposure and selenite inhibited, at least in part, the Hg-induced oxidation of renal and hepatic NPSH. Se(4+) and Hg(2+), when injected alone, did not alter hepatic or renal TBARS levels; however, simultaneous exposure to these compounds increased hepatic and renal TBARS levels at 12 and 48 h after treatment, respectively. Present results suggest that selenium abolishes the interaction of Hg(2+) with sulfhydryl groups of protein and nonprotein sources.

Animals↗

PubMed2003

In vitro effects of selenite and mercuric chloride on liver thiobarbituric acid-reactive substances and non-protein thiols from rats: influences of dietary cholesterol and polyunsaturated and saturated fatty acids.

OBJECTIVE: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. METHODS: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h. RESULTS: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. CONCLUSION: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.

Animals↗

PubMed2003

Interaction between metals and chelating agents affects glutamate binding on brain synaptic membranes.

The present study investigates the possible effects of Hg2+, Pb2+, and Cd2+ on [3H]-glutamate binding. To better understand the role of the thiol-disulfide status on the toxicity of such metals toward glutamatergic neurotransmission, we used three thiol chelating agents, 2,3-dimercaptopropanol (BAL), 2,3-dimercaptopropane 1-sulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid (DMSA). Dithiotreitol (DTT) was tested for its ability to prevent metals-induced inhibition on [3H]-glutamate binding. Hg2+, Pb2+, and Cd2+ showed a concentration-dependent inhibition on [3H]-glutamate binding, and mercury was the most effective inhibitor. BAL did not prevent [3H]-glutamate binding inhibition by Hg2+, Cd2+, and Pb2+. However, DMPS and DMSA prevented the inhibition caused by Cd2+ and Pb2+, but not by Hg2+. DTT did not prevent the inhibition on [3H]-glutamate binding caused by 10 microM Hg2+. In contrast, it was able to partially prevent [3H]-glutamate binding inhibition caused by 40 microM Pb2+ and Cd2+. These results demonstrated that the heavy metals present an inhibitory effect on [3H]-glutamate binding. In addition, BAL was less effective to protect [3H]-glutamate binding inhibition caused by these metals than other chelating agents studied.

Animals↗