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[show abstract]
[hide abstract]
ABSTRACT: This study was undertaken in order to characterize the role of the glutamate/aspartate transporter (GLAST) in the glutathione (GSH) efflux induced by glutamate. Our results demonstrated that retinal cell cultures exhibit two mechanisms of GSH release, one Na(+)-independent and other Na(+)-dependent. Glutamate and aspartate induced GSH efflux only in presence of Na(+). Treatment with PCD (L-trans-Pyrrolidine-2,4-dicarboxylate), a transportable glutamate uptake blocker, increased GSH release indicating that GSH can be carried by glutamate transporters in retinal cell cultures. Added to this, treatment with zinc ion cultures, a recognized inhibitor of GLAST blocked GSH efflux evoked by glutamate. Treatment with NMDA antagonist (MK-801) did not have any effect on the GSH release induced by glutamate. These results suggest that glutamate induces GLAST-mediated release of GSH from retinal cell cultures and this could represent an important mechanism of cellular protection against glutamate toxicity in the CNS.
Neurochemical Research 03/2011; 36(3):412-8. · 2.24 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: This paper presents a review about mercury contamination and human exposure in the Tapajós River basin (Brazil), one of the major tributaries of the Amazon impacted by traditional gold mining from the mid 1980s. The most recent review in this region was published more than ten years ago and since then many articles about environment and especially human populations have revealed new aspects of mercury toxicology. Additionally, new biomarkers of mercury exposure and toxicity have been studied in these populations. However, there are still many open, about both mercury's biogeochemical cycle and mercury health risks. Further environmental and human risk research directions are proposed.
Environment international 08/2010; 36(6):593-608. · 4.79 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Thiamethoxam is a neonicotinoid insecticide, a group of pesticides that acts selectively on insect nicotinic acetylcholine receptors (nAChRs), with only a little action on mammalian nAChRs. Nevertheless, the selectivity of neonicotinoids for the insect nAChRs may change when these substances are metabolized. Therefore, we aimed to determine the potential effects of thiamethoxam on mammalian brain, testing the performance in the open field and elevated plus-maze of rats exposed to this insecticide and, in order to establish the neurochemical endpoints, we measured the acetylcholinesterase activity in different brain regions (hippocampus, striatum and cortex) and the high-affinity choline uptake (HACU) in synaptosomes from rat hippocampus. Treated animals received thiamethoxam (25, 50 or 100mg/kg) for 7 consecutive days. The results showed that treatment with thiamethoxam induced an increase in the anxiety behavior at two doses (50 or 100mg/kg). Moreover, there was a significant decrease in both HACU and acetylcholinesterase activity. Our hypothesis is that thiamethoxam (or its metabolites) could be acting on the central rats nAChRs. This would produce an alteration on the cholinergic transmission, modulating the anxiety behavior, acetylcholinesterase levels and HACU.
Ecotoxicology and Environmental Safety 06/2009; 73(1):101-7. · 2.29 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Physalis angulata is a popular medicine used in Brazil due to its anti-inflammatory effects, but the pharmacological mechanisms underlying these actions remain to be better understood. In the present work, lyophilized aqueous extract from the roots of Physalis angulata Linneu (AEPa) was used to control the inflammatory response induced by the injection of 1% carrageenan into subcutaneous rat's air pouches. Adenosine deaminase (ADA) activity, nitrite level, and prostaglandin E(2) (PGE(2)) level were used to evaluate the action of inflammatory mediators. Tumor growth factor-beta (TGF-beta) level was used as a bioindicator of immunomodulatory response. Rats were injected with vehicle, indomethacin, or AEPa (0.5 mg/kg, 1 mg/kg, and 5 mg/kg i.p.), 1h before carrageenan administration. AEPa at 0.5 mg/kg had no effect. However, 1mg/kg of AEPa showed significant anti-inflammatory effects, decreasing exudate volume, total number of inflammatory cells, ADA activity, nitrite level, and PGE(2) level in 50%, 41%, 20%, 60%, and 41%, respectively. The anti-inflammatory effects of 5 mg/kg AEPa appeared to be more effective than those of 1 mg/kg AEPa (84%, 80%, 43%, 70%, and 75%, respectively). In addition, TGF-beta level was upregulated to 9700 pg/ml after 5mg/kg AEPa, in comparison with 160 pg/ml in the vehicle-treated group, and 137 pg/ml in the indomethacin-treated group. The results indicate that AEPa exerts powerful anti-inflammatory and immunomodulatory activities, interfering with the cyclooxygenase pathway, lymphocyte proliferation, NO, and TGF-beta production.
Journal of Ethnopharmacology 08/2008; 118(2):246-51. · 3.01 Impact Factor
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M C N Pinheiro,
B M Macchi,
J L F Vieira,
T Oikawa,
W W Amoras,
G A Guimarães,
C A Costa,
M E Crespo-López,
A M Herculano,
L C L Silveira, J L M do Nascimento
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[hide abstract]
ABSTRACT: Mercury is a hazardous metal that has become an important issue of environmental contamination in Amazon areas. Human intoxication by mercury causes sensory deficits, motor dysfunction, delayed psychomotor development, genotoxicity, and several other health problems. One of the major cellular mechanisms of mercury toxicity is the oxidative stress which may lead to membrane peroxidation and generation of reactive oxygen species. The antioxidant defense, which includes scavenger compounds such as glutathione and antioxidant enzymes such as catalase, might prevent these injuries to occur. Thus, the objective of this work was to evaluate hair mercury levels and the strength of antioxidant defenses, evaluated by glutathione levels and catalase activity in the blood of exposed and non-exposed women living in Amazon populations. For each location, no statistically significant difference (P<0.05) was detected for age versus mercury content. However, women from populations under the influence of gold mining activity exhibit high mercury levels in hair samples, above the tolerance limit accepted by the World Health Organization. In addition, a significant correlation was found between high mercury content, high glutathione level, and lower catalase activity. These data suggest that chronic mercury intoxication may deplete antioxidant enzymatic activity, which can be used as an important peripheral marker. Knowledge originated by this monitoring will better assist the development of preventive strategies and governmental actions against the problem of mercury contamination.
Environmental Research 06/2008; 107(1):53-9. · 3.40 Impact Factor
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M C N Pinheiro,
M E Crespo-López,
J L F Vieira,
T Oikawa,
G A Guimarães,
C C Araújo,
W W Amoras,
D R Ribeiro,
A M Herculano, J L M do Nascimento,
L C L Silveira
[show abstract]
[hide abstract]
ABSTRACT: Mercury is a hazardous metal responsible for environmental contamination and human intoxication. Methylmercury, a very toxic organic compound, bio-accumulates through food chain, and is responsible for chronic mercury exposure of riverside Amazonian communities with a diet rich in fish. Uncertainties about the reference exposure dose that could have damaging consequences for nervous system development makes necessary the biomonitoring of these Amazonian populations, especially children. In this work, a comparative study was performed in exposed and non-exposed children living in the Amazon. A total of 168 children were analyzed to find possible correlations between gender, age, location, and hair mercury content. For each location, no statistically significant differences (P<0.05) were detected for gender and age versus mercury content. However, mean mercury levels in hair samples may indicate a tendency of boys to average higher hair concentrations. Also, in the community with highest levels of mercury, the limit of 10 micro g/g of mercury was surpassed by 65% of 2-6 years and 50% of 7-12 years children but only by 27% of 0-1 year babies, pointing to a lower bioaccumulation and/or the existence of a protection mechanism in babies. Log normal distributions of mercury concentrations for each location showed that children from populations under influence of gold mining activity contain the highest mercury levels in hair samples, though this intoxication may have decreased when compared to previous studies. Knowledge originated by this monitoring will better assist in the development of prevention strategies and government actions targeting the mercury contamination of Amazonian environment.
Environment International 02/2007; 33(1):56-61. · 5.30 Impact Factor
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[hide abstract]
ABSTRACT: The visual system is a potential target for methylmercury (MeHg) intoxication. Nevertheless, there are few studies about the cellular mechanisms of toxicity induced by MeHg in retinal cells. Various reports have indicated a critical role for nitric oxide synthase (NOS) activation in modulating MeHg neurotoxicity in cerebellar and cortical regions. The aim of the present study is to describe the effects of MeHg on cell viability and NOS activation in chick retinal cell cultures. For this purpose, primary cultures were prepared from 7-day-old chick embryos: retinas were aseptically dissected and dissociated and cells were grown at 37 degrees C for 7-8 days. Cultures were exposed to MeHg (10 microM, 100 microM, and 1 mM) for 2, 4, and 6 h. Cell viability was measured by MTT method and NOS activity by monitoring the conversion of L-[H3]-arginine to L-[H3]-citrulline. The incubation of cultured retina cells with 10 and 100 microM MeHg promoted an increase of NOS activity compared to control (P < 0.05). Maximum values (P < 0.05) were reached after 4 h of MeHg incubation: increases of 81.6 +/- 5.3 and 91.3 +/- 3.7%, respectively (data are reported as mean +/- SEM for 4 replicates). MeHg also promoted a concentration- and time-dependent decrease in cell viability, with the highest toxicity (a reduction of about 80% in cell viability) being observed at the concentration of 1 mM and after 4-6 h of incubation. The present study demonstrates for the first time the modulation of MeHg neurotoxicity in retinal cells by the nitrergic system.
Brazilian Journal of Medical and Biological Research 04/2006; 39(3):415-8. · 1.13 Impact Factor
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[hide abstract]
ABSTRACT: In this study, we attempted to identify the possible antinociceptive action of aqueous extract (AE) obtained from roots of Physalis angulata, known in Brazil as "Camapu", used to treat various pain-related physiological conditions. The AE of Physalis angulata (10-30 mg/kg) given by i.p. or p.o. route, 0.5 and 1h prior, produced significant inhibition of abdominal constrictions caused by acetic acid, with ID(50) values of 18.5 (17.4-19.8) and 21.5 (18.9-24.4)mg/kg and inhibitions of 83+/-8 and 66+/-5%, respectively. The AE (10-60 mg/kg, i.p.) also caused significant inhibition of the late-phase of formalin-induced pain, with an ID(50) value of 20.8 (18.4-23.4)mg/kg and inhibition of 100%. Treatment of mice with AE (60 mg/kg, i.p.) or with morphine (10mg/kg, i.p.) produced a significant increase of the reaction time in the hot-plate test. These results demonstrate, for the first time, that the AE of Physalis angulata produce marked antinociception against the acetic acid-induced visceral pain and inflammatory pain responses induced by formalin in mice. The mechanism by which the AE produces antinociception still remains unclear. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in Physalis angulata. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.
Journal of Ethnopharmacology 02/2006; 103(2):241-5. · 3.01 Impact Factor
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[hide abstract]
ABSTRACT: The aim of the present study was to evaluate mercury and selenium concentrations in hair samples of reproductive age women from riverside communities of the Tapajós River basin. We studied 19 pregnant and 21 non-pregnant women, 13 to 45 years old, living in the region for at least 2 years, and having a diet rich in fish. The analysis of Se and total Hg were performed in the Instituto de Pesquisas Energéticas e Nucleares (IPEN, São Paulo, Brazil) by using a Varian AA220-FS atomic absorption spectrometer with a flow injection system. There were no differences between the two groups - pregnant and non-pregnant -- concerning age (23.80 +/- 6.92 and 26.60 +/- 9.60 years old, respectively) and residential time (20.21 +/- 8.30 and 22.20 +/- 10.90 years, respectively). The geometric means and ranges for total Hg concentration were similar (p > 0.05): 8.25 microg/g (1.51-19.43) in pregnant and 9.39 microg/g (5.25-21.00) in non-pregnant women, respectively. Total Hg concentrations were also similar in different gestational stages. However, there was a significant difference between the two groups (p < 0.05, Student t test) in relation to Se concentration: 0.61 microg/g (0.40-2.33) in pregnant and 2.46 microg/g (0.92-5.74) in non-pregnant women, respectively. We concluded that Hg exposure levels in reproductive age women were only slightly higher than a provisional tolerable weekly intake of MeHg would provide, that Hg concentration in maternal hair samples was independent of gestational age, and that low Se concentration in pregnant women indicates high mineral consumption by fetal organism to satisfy their metabolic requirements raised during pregnancy, including as a protective mechanism for Hg cytotoxic effects.
Science of The Total Environment 10/2005; 349(1-3):284-8. · 3.29 Impact Factor
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ABSTRACT: The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 microM increased extracellular DA levels to 1941 +/- 199% in terms of basal levels. Infusion of MeHg 400 microM in GSH 400 microM pretreated animals, only increased striatal DA levels to 465 +/- 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 microM after infusion of GSH 400 microM increased DA levels to 1019 +/- 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 microM in CYS 400 microM -pretreated animals, increased striatal DA levels to 740 +/- 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 microM in MET 400 microM pretreated animals increased striatal DA levels to 2011 +/- 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 muM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with -SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.
Life Sciences 07/2005; 77(4):444-51. · 2.53 Impact Factor
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[hide abstract]
ABSTRACT: The present study was carried out in order to determine the effects of intrastriatal administration of different doses (40 microM, 400 microM, and 4mM) of methylmercury (MeHg) on dopaminergic system of rat striatum. Experiments were performed in conscious and freely moving rats using brain microdialysis coupled with liquid chromatography. Intrastriatal administration of MeHg produced significant increases in dopamine (DA) striatal levels (907+/-7%, 1870+/-319%, and 7971+/-534% for the doses of 40, 400 microM, and 4mM, with respect to basal). The increase in DA levels was associated with significant decreases in extracellular levels of its main metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) (65.0+/-3.0% and 52.2+/-1.3%, respectively) using the dose of 4mM MeHg, whereas nonsignificant changes in metabolite levels were observed with the doses of 40 and 400 microM MeHg. A second infusion of 4mM MeHg 24h after first infusion also produced a rise of DA levels, but this increase was very small as compared with that produced by first infusion (7971+/-534% versus 985+/-186%). This second infusion of 4mM MeHg also decreased DOPAC and HVA levels, but this decrease was not significant as compared with that observed after first infusion (65.0+/-3.0% and 52.2+/-1.3% versus 62.4+/-5.2% and 63.4+/-7.4%, respectively). We discuss these effects based on a stimulated DA release and/or a decreased DA intraneuronal degradation.
Ecotoxicology and Environmental Safety 07/2003; 55(2):173-7. · 2.29 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The possible protective effects of NMDA receptor antagonists dizocilpine (MK-801) and D(-)-2-amino-5-phosphonopentanoic acid (AP5), and nitric oxide synthase (NOS) inhibitors L-nitro-arginine methyl ester (L-NAME) and 7-nitro-indazol (7-NI) on the methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis. Intrastriatal infusion of 400 microM or 4 mM MeHg increased the extracellular DA levels to 1941+/-199 and 7971+/-534% with respect to basal levels. Infusion of 400 microM or 4 mM MeHg in 400 microM MK-801 pretreated animals, increased striatal DA levels to 677+/-126 and 2926+/-254%, with respect to basal levels, these increases being 65 and 63% smaller than those induced by MeHg in non-pretreated animals. Infusion of 400 microM or 4 mM MeHg in 400 microM AP5 pretreated animals, increased striatal DA levels to 950+/-234 and 2251+/-254% with respect to basal levels, these increases being 51 and 72% smaller than those induced by MeHg in non-pretreated animals. Infusion of 400 microM MeHg in 100 microM L-NAME or 7-NI pretreated animals, increased the extracellular DA levels to 1159+/-90 and 981+/-292%, with respect to basal levels, these increases being 40 and 50% smaller than those induced by MeHg in non-pretreated animals. In summary, MeHg acts, at last in part, through an overstimulation of NMDA receptors with possible NO production to induce DA release, and administration of NMDA receptor antagonists and NOS inhibitors protects against MeHg-induced DA release from rat striatum.
Neuropharmacology 05/2002; 42(5):612-8. · 4.81 Impact Factor
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ABSTRACT: Methylmercury (MeHg) produces significant increases in the spontaneous output of dopamine (DA) from rat striatal tissue. The mechanism through MeHg produces such increase in the extracellular DA levels could be due to increased DA release or decreased DA uptake into DA terminals. One of the aims of this study was to investigate the role of DA transporter (DAT) in the MeHg-induced DA release. Coinfusion of 400 microM MeHg and nomifensine (50 microM) or amphetamine (50 microM) produced increases in the release of DA similar to those produced by nomifensine and amphetamine alone. In the same way, MeHg-induced DA release was not attenuated under Ca(2+)-free conditions or after pretreatment with reserpine (10 mg/kg i.p.) or tetrodotoxin (TTX), suggesting that the DA release was independent of calcium and vesicular stores, as well as it was not affected by the blockade of voltage sensitive sodium channels. Thus, to investigate whether depolarization of dopaminergic terminal was able to affect MeHg-induced DA release, we infused 75 mM KCl through the dialysis membrane. Our results clearly showed a decrease induced by MeHg in the KCl-evoked DA release. Taken together, these results suggest that MeHg induces release of DA via transporter-dependent, calcium- and vesicular-independent mechanism and it decreases the KCl-evoked DA release.
Neurochemistry International 05/2002; 40(5):455-65. · 2.86 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: In this study, we attempted to identify the possible antinociceptive action of aqueous extract (AE) obtained from roots of Physalis angulata, known in Brazil as “Camapu”, used to treat various pain-related physiological conditions. The AE of Physalis angulata (10–30 mg/kg) given by i.p. or p.o. route, 0.5 and 1 h prior, produced significant inhibition of abdominal constrictions caused by acetic acid, with ID50 values of 18.5 (17.4–19.8) and 21.5 (18.9–24.4) mg/kg and inhibitions of 83 ± 8 and 66 ± 5%, respectively. The AE (10–60 mg/kg, i.p.) also caused significant inhibition of the late-phase of formalin-induced pain, with an ID50 value of 20.8 (18.4–23.4) mg/kg and inhibition of 100%. Treatment of mice with AE (60 mg/kg, i.p.) or with morphine (10 mg/kg, i.p.) produced a significant increase of the reaction time in the hot-plate test. These results demonstrate, for the first time, that the AE of Physalis angulata produce marked antinociception against the acetic acid-induced visceral pain and inflammatory pain responses induced by formalin in mice. The mechanism by which the AE produces antinociception still remains unclear. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in Physalis angulata. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.
Journal of Ethnopharmacology.
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[show abstract]
[hide abstract]
ABSTRACT: This paper presents a review about mercury contamination and human exposure in the Tapajós River basin (Brazil), one of the major tributaries of the Amazon impacted by traditional gold mining from the mid 1980s. The most recent review in this region was published more than ten years ago and since then many articles about environment and especially human populations have revealed new aspects of mercury toxicology. Additionally, new biomarkers of mercury exposure and toxicity have been studied in these populations. However, there are still many open, about both mercury's biogeochemical cycle and mercury health risks. Further environmental and human risk research directions are proposed.
Environment International.
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[show abstract]
[hide abstract]
ABSTRACT: In the present study, the effects of intrastriatal administration of different concentrations (40 μM, 400 μM, and 4 mM) of inorganic mercury (HgCl2) on the dopaminergic system of rat striatum were evaluated, using a microdialysis technique coupled to liquid chromatography-electrochemical detection. In previous studies, we discussed the effects of organic mercury (MeHg) administration on the striatal dopaminergic system on the basis of changes in the release and metabolism of striatal dopamine (DA). In the present study it is demonstrated that intrastriatal administration of all concentrations of HgCl2 produced significant increases in the output of DA (1240, 2500, and 2658% for the concentrations of 40 μM, 400 μM, and 4 mM HgCl2, respectively) from rat striatal tissue, associated with significant decreases in striatal levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) with the concentrations of 400 μM and 4 mM HgCl2 (74.4 and 3.4% for DOPAC and 71.0 and 50.6% for HVA, respectively), whereas no changes in metabolite levels were observed with the concentration of 40 μM HgCl2. These effects are explained as a result of stimulated DA release and/or changed DA metabolism. The effects of intrastriatal administration of HgCl2 were compared with those of MeHg on DA extracellular levels.
Ecotoxicology and Environmental Safety.
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[show abstract]
[hide abstract]
ABSTRACT: Physalis angulata is a popular medicine used in Brazil due to its anti-inflammatory effects, but the pharmacological mechanisms underlying these actions remain to be better understood. In the present work, lyophilized aqueous extract from the roots of Physalis angulata Linneu (AEPa) was used to control the inflammatory response induced by the injection of 1% carrageenan into subcutaneous rat's air pouches. Adenosine deaminase (ADA) activity, nitrite level, and prostaglandin E2 (PGE2) level were used to evaluate the action of inflammatory mediators. Tumor growth factor-β (TGF-β) level was used as a bioindicator of immunomodulatory response. Rats were injected with vehicle, indomethacin, or AEPa (0.5 mg/kg, 1 mg/kg, and 5 mg/kg i.p.), 1 h before carrageenan administration. AEPa at 0.5 mg/kg had no effect. However, 1 mg/kg of AEPa showed significant anti-inflammatory effects, decreasing exudate volume, total number of inflammatory cells, ADA activity, nitrite level, and PGE2 level in 50%, 41%, 20%, 60%, and 41%, respectively. The anti-inflammatory effects of 5 mg/kg AEPa appeared to be more effective than those of 1 mg/kg AEPa (84%, 80%, 43%, 70%, and 75%, respectively). In addition, TGF-β level was upregulated to 9700 pg/ml after 5 mg/kg AEPa, in comparison with 160 pg/ml in the vehicle-treated group, and 137 pg/ml in the indomethacin-treated group. The results indicate that AEPa exerts powerful anti-inflammatory and immunomodulatory activities, interfering with the cyclooxygenase pathway, lymphocyte proliferation, NO, and TGF-β production.
Journal of Ethnopharmacology.
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[show abstract]
[hide abstract]
ABSTRACT: Thiamethoxam is a neonicotinoid insecticide, a group of pesticides that acts selectively on insect nicotinic acetylcholine receptors (nAChRs), with only a little action on mammalian nAChRs. Nevertheless, the selectivity of neonicotinoids for the insect nAChRs may change when these substances are metabolized. Therefore, we aimed to determine the potential effects of thiamethoxam on mammalian brain, testing the performance in the open field and elevated plus-maze of rats exposed to this insecticide and, in order to establish the neurochemical endpoints, we measured the acetylcholinesterase activity in different brain regions (hippocampus, striatum and cortex) and the high-affinity choline uptake (HACU) in synaptosomes from rat hippocampus. Treated animals received thiamethoxam (25, 50 or 100 mg/kg) for 7 consecutive days. The results showed that treatment with thiamethoxam induced an increase in the anxiety behavior at two doses (50 or 100 mg/kg). Moreover, there was a significant decrease in both HACU and acetylcholinesterase activity. Our hypothesis is that thiamethoxam (or its metabolites) could be acting on the central rats nAChRs. This would produce an alteration on the cholinergic transmission, modulating the anxiety behavior, acetylcholinesterase levels and HACU.
Ecotoxicology and Environmental Safety.
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[show abstract]
[hide abstract]
ABSTRACT: The possible protective effects of glutathione (GSH), cysteine (CYS) and methionine (MET) on the Methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis coupled to HPLC with electrochemical detection. Intrastriatal infusion of MeHg 400 μM increased extracellular DA levels to 1941 ± 199% in terms of basal levels. Infusion of MeHg 400 μM in GSH 400 μM pretreated animals, only increased striatal DA levels to 465 ± 104%, in terms of basal levels, this increase being 76% lower than induced by MeHg alone. Conversely, the infusion of MeHg 400 μM after infusion of GSH 400 μM increased DA levels to 1019 ± 96% in terms of basal levels, this increase being 47.5% lower than that observed in MeHg non-pretreated animals. The infusion of MeHg 400 μM in CYS 400 μM -pretreated animals, increased striatal DA levels to 740 ± 149%, in terms of basal levels, this increase being 62% lower than that induced by MeHg in non-pretreated animals. The infusion of MeHg 400 μM in MET 400 μM pretreated animals increased striatal DA levels to 2011 ± 230% in terms of basal, an increase that was not significantly different from that produced by MeHg 400 μM alone. In summary, the administration of compounds containing free -SH groups prevented the MeHg-induced DA release from rat striatum, probably due to the binding of MeHg to -SH groups. This would result in a lower metal availability to interact with –SH membrane proteins groups, which would decrease MeHg ability to interact with DA transporter.
Life Sciences.
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[show abstract]
[hide abstract]
ABSTRACT: The possible protective effects of NMDA receptor antagonists dizocilpine (MK-801) and d(−)-2-amino-5-phosphonopentanoic acid (AP5), and nitric oxide synthase (NOS) inhibitors l-nitro-arginine methyl ester (l-NAME) and 7-nitro-indazol (7-NI) on the methylmercury (MeHg)-induced dopamine (DA) release from rat striatum were investigated using in vivo microdialysis. Intrastriatal infusion of 400 μM or 4 mM MeHg increased the extracellular DA levels to 1941±199 and 7971±534% with respect to basal levels. Infusion of 400 μM or 4 mM MeHg in 400 μM MK-801 pretreated animals, increased striatal DA levels to 677±126 and 2926±254%, with respect to basal levels, these increases being 65 and 63% smaller than those induced by MeHg in non-pretreated animals. Infusion of 400 μM or 4 mM MeHg in 400 μM AP5 pretreated animals, increased striatal DA levels to 950±234 and 2251±254% with respect to basal levels, these increases being 51 and 72% smaller than those induced by MeHg in non-pretreated animals. Infusion of 400 μM MeHg in 100 μM l-NAME or 7-NI pretreated animals, increased the extracellular DA levels to 1159±90 and 981±292%, with respect to basal levels, these increases being 40 and 50% smaller than those induced by MeHg in non-pretreated animals. In summary, MeHg acts, at last in part, through an overstimulation of NMDA receptors with possible NO production to induce DA release, and administration of NMDA receptor antagonists and NOS inhibitors protects against MeHg-induced DA release from rat striatum.
Neuropharmacology.
