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Cristina W Nogueira - One of the best experts on this subject based on the ideXlab platform.
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efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice
Toxicology Letters, 2007Co-Authors: Cristiane Luchese, Cristina W Nogueira, Ricardo Brandao, Renata De Oliveira, Francielli Weber SantosAbstract:Abstract This study was designed to examine if diphenyl diselenide (PhSe) 2 , an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl 2 . Male adult Swiss albino mice received CdCl 2 (10 μmol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe) 2 (10 μmol/kg or 20 μmol/kg, orally) was given concomitantly with CdCl 2 to mice. A number of Toxicological Parameters in lung and brain of mice were examined including δ-aminolevulinic acid dehydratase (δ-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na + ,K + -ATPase activity, acetylcholinesterase (AChE) activity, [ 3 H]glutamate uptake and [ 3 H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe) 2 at the dose of 20 μmol/kg protected the inhibition of δ-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl 2 in lungs. At 10 μmol/kg, (PhSe) 2 protected cerebral AChE and CAT activities inhibited by CdCl 2 . There were no histopathological alterations in the lung of mice after CdCl 2 exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl 2 than in control mice. (PhSe) 2 at dose of 20 μmol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe) 2 attenuated the oxidative damage induced by CdCl 2 in lung and brain of mice.
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low toxicity of diphenyl diselenide in rabbits a long term study
Basic & Clinical Pharmacology & Toxicology, 2007Co-Authors: Andreza Fabro De Bem, Marcelo Farina, Cristina W Nogueira, Rafael De Lima Portella, Juliano Perottoni, Marcio W Paixao, João RochaAbstract:1 Department of Clinical and Toxicological Analysis, Center for Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, and 'Department of Biochemistry, Center for Biological Sciences, Federal University of Santa Catarina, Florianopolis, SC, Brazil Selenium compounds, like diphenyl diselenide (Ph 2 Se 2 ), possess glutathione peroxidase (GSHPx)-like activities and other antioxidant properties. The aim of this study was to evaluate the effects of a long-term oral supplementation with Ph 2 Se 2 on various Toxicological Parameters in rabbits. Adult New Zealand male rabbits were divided into four groups: Group I served as control; Groups II, III and IV received 0.3, 3.0 and 30 p.p.m. of Ph 2 Se 2 pulverized in the chow for 8 months. A number of Toxicological Parameters were examined in liver, kidney, cerebral cortex and hippocampus, such as 8-aminolaevulinic acid dehydratase (δ-ALA-D), catalase (CAT), GSHPx activities, non-protein thiol (-SH), lipid peroxidation and ascorbic acid levels. The results indicated that supplementation 30 p.p.m. Ph 2 Se 2 significantly increased 8-ALA-D activity in liver and in cerebral cortex. Non-protein -SH levels were significantly increased in liver but not in kidney, cerebral cortex and hippocampus of rabbits. Ascorbic acid content was significantly lower in the liver and cerebral cortex after supplementation with 30 p.p.m. Ph 2 Se 2 . Conversely, no alterations in GSHPx and CAT activities, nor in thiobarbituric acid reactive substances levels were observed in rabbit tissues. These results indicate that oral supplementation with Ph 2 Se 2 is relatively secure in rabbits after 8 months of exposure. The findings encourage further experiments on the potential therapeutic effects of such compound.
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efficacy of 2 3 dimercapto 1 propanesulfonic acid dmps and diphenyl diselenide on cadmium induced testicular damage in mice
Food and Chemical Toxicology, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Paulo Do C Nascimento, Marieli S Marques, Cristina W NogueiraAbstract:Abstract The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl 2 (2.5 or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined, such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) and diphenyl diselenide (PhSe) 2 were studied. The results demonstrated an inhibition of δ-ALA-D activity, a reduction of ascorbic acid and an increase of lipid peroxidation induced by cadmium, indicating testes damage. Furthermore, we observed an increase of plasma LDH, AST and ALT activities. DMPS (400 mol/kg) and (PhSe) 2 (100 μmol/kg) partially protected from the inhibitory effect of 2.5 mg/kg CdCl 2 on δ-ALA-D and from the increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe) 2 therapy was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5 mg/kg. Treatment with DMPS and (PhSe) 2 , individually or combined, was inefficient in reducing cadmium-induced plasma LDH and ALT activity increase. The use of combined therapy (DMPS plus (PhSe) 2 ) proved to be efficient in decreasing cadmium levels in testes and in ameliorating plasma AST activity from animals that received the highest dose of cadmium.
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diphenyl diselenide reverses cadmium induced oxidative damage on mice tissues
Chemico-Biological Interactions, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Simone Nardin Weis, Juliana M Fachinetto, Alexandre M Favero, Cristina W NogueiraAbstract:The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of Toxicological Parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma Parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.
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cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice
Toxicology Letters, 2004Co-Authors: Francielli Weber Santos, João Rocha, Tatiana Oro, Gilson Zeni, Paulo Do C Nascimento, Cristina W NogueiraAbstract:Abstract Acute effects of cadmium in mice testes were evaluated. Animals received a single dose of CdCl2 (2.5 mg/kg or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible protective effect of meso-2,3-dimercaptosuccinic acid (DMSA) and diphenyl diselenide (PhSe)2 are studied. The results demonstrated inhibition of δ-ALA-D and SOD activities, reduction in ascorbic acid, increase of lipid peroxidation induced by cadmium, indicating testes damage. DMSA (400 μmol/Kg) and (PhSe)2 (100 μmol/Kg) protected inhibitory effect of 2.5 mg/kg CdCl2 on δ-ALA-D and restored the increase of TBARS levels. Otherwise, (PhSe)2 treatment was effective in reducing the increase of TBARS levels induced by 5 mg/kg CdCl2, whereas DMSA and (PhSe)2, in combination, were ineffective in reducing TBARS level. However, these compounds alone or in combination, were unable to protect SOD activity and to improve ascorbic acid levels near to the normal value. The use of combined therapy (DMSA plus (PhSe)2) not proved be better than the monotherapy, in improving Toxicological Parameters evaluated in this model of testicular damage induced by cadmium.
Monique Rennen - One of the best experts on this subject based on the ideXlab platform.
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derivation of the minimal magnitude of the critical effect size for continuous Toxicological Parameters from within animal variation in control group data
Regulatory Toxicology and Pharmacology, 2009Co-Authors: Harrie Buist, Jan Telman, Frhr G Von Bolcshazy, M Dammann, Monique RennenAbstract:Assuming that temporal fluctuations in physiological Parameters (e.g. haematology, biochemistry) in individual healthy non-exposed animals are non-adverse, the minimal magnitude of the Critical Effect Size (CES) for a number of continuous Parameters of toxicity studies was derived. A total of 36 studies (19 pharmaceutical preclinical studies in dogs and 17 chemical risk assessment studies in rats) were analysed to determine within-animal variation in their control groups. Minimal CES-values were derived for each group of studies, differentiating where necessary between strains and sexes, using the 2.5 percentile (lower limit) and/or 97.5 percentile (upper limit) of the distribution of the within-animal variation around the mean of each parameter. We concluded that minimal CES-values for continuous clinical chemistry and haematology Parameters should be established separately per species, strain, sex and study duration investigated. Grouping of minimal CES-values, leading to more or less "general" values, seems possible for those Parameters that are subject to tight homeostatic control and consequently show little within-animal variation. Nearly a quarter of the proposed CES-values is ≤5%, nearly a quarter range from 6% to 10%, a quarter is 15% or 20%, and nearly 30% of the proposed values is ≥20% of the mean of the control animals. © 2009 Elsevier Inc. All rights reserved.
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within animal variation as an indication of the minimal magnitude of the critical effect size for continuous Toxicological Parameters applicable in the benchmark dose approach
Risk Analysis, 2006Co-Authors: Susan Dekkers, Jan Telman, Monique Rennen, Marco J Appel, Cees De HeerAbstract:In this study, the within-animal variation in routinely studied continuous Toxicological Parameters was estimated from temporal fluctuations in individual healthy nonexposed animals. Assuming that these fluctuations are nonadverse, this within-animal variation may be indicative of the minimal magnitude of the critical effect size (CES). The CES is defined as the breaking point between adverse and nonadverse changes in a continuous Toxicological parameter, at the level of the individual organism. The total variation in the data from individual nonexposed animals was divided in variation parts due to known factors (differences in sex, animal, and day) and a residual variation, by means of analysis of variance. Using the residual variation and the estimated analytical measurement error of a Toxicological parameter, the within-animal variation can be estimated. The data showed within-animal variations ranging between 0.6% and 34% for different clinical chemistry and hematological Parameters in 90-day rat studies. This indicates that different (minimal) CES values may be applicable for different Parameters. © 2006 Society for Risk Analysis.
João Rocha - One of the best experts on this subject based on the ideXlab platform.
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toxicity of ethylmercury and thimerosal a comparison with methylmercury
Journal of Applied Toxicology, 2013Co-Authors: José G. Dórea, Marcelo Farina, João RochaAbstract:Ethylmercury (etHg) is derived from the metabolism of thimerosal (o-carboxyphenyl-thio-ethyl-sodium salt), which is the most widely used form of organic mercury. Because of its application as a vaccine preservative, almost every human and animal (domestic and farmed) that has been immunized with thimerosal-containing vaccines has been exposed to etHg. Although methylmercury (meHg) is considered a hazardous substance that is to be avoided even at small levels when consumed in foods such as seafood and rice (in Asia), the World Health Organization considers small doses of thimerosal safe regardless of multiple/repetitive exposures to vaccines that are predominantly taken during pregnancy or infancy. We have reviewed in vitro and in vivo studies that compare the Toxicological Parameters among etHg and other forms of mercury (predominantly meHg) to assess their relative toxicities and potential to cause cumulative insults. In vitro studies comparing etHg with meHg demonstrate equivalent measured outcomes for cardiovascular, neural and immune cells. However, under in vivo conditions, evidence indicates a distinct toxicokinetic profile between meHg and etHg, favoring a shorter blood half-life, attendant compartment distribution and the elimination of etHg compared with meHg. EtHg's toxicity profile is different from that of meHg, leading to different exposure and toxicity risks. Therefore, in real-life scenarios, a simultaneous exposure to both etHg and meHg might result in enhanced neurotoxic effects in developing mammals. However, our knowledge on this subject is still incomplete, and studies are required to address the predictability of the additive or synergic Toxicological effects of etHg and meHg (or other neurotoxicants).
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low toxicity of diphenyl diselenide in rabbits a long term study
Basic & Clinical Pharmacology & Toxicology, 2007Co-Authors: Andreza Fabro De Bem, Marcelo Farina, Cristina W Nogueira, Rafael De Lima Portella, Juliano Perottoni, Marcio W Paixao, João RochaAbstract:1 Department of Clinical and Toxicological Analysis, Center for Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Department of Chemistry, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, and 'Department of Biochemistry, Center for Biological Sciences, Federal University of Santa Catarina, Florianopolis, SC, Brazil Selenium compounds, like diphenyl diselenide (Ph 2 Se 2 ), possess glutathione peroxidase (GSHPx)-like activities and other antioxidant properties. The aim of this study was to evaluate the effects of a long-term oral supplementation with Ph 2 Se 2 on various Toxicological Parameters in rabbits. Adult New Zealand male rabbits were divided into four groups: Group I served as control; Groups II, III and IV received 0.3, 3.0 and 30 p.p.m. of Ph 2 Se 2 pulverized in the chow for 8 months. A number of Toxicological Parameters were examined in liver, kidney, cerebral cortex and hippocampus, such as 8-aminolaevulinic acid dehydratase (δ-ALA-D), catalase (CAT), GSHPx activities, non-protein thiol (-SH), lipid peroxidation and ascorbic acid levels. The results indicated that supplementation 30 p.p.m. Ph 2 Se 2 significantly increased 8-ALA-D activity in liver and in cerebral cortex. Non-protein -SH levels were significantly increased in liver but not in kidney, cerebral cortex and hippocampus of rabbits. Ascorbic acid content was significantly lower in the liver and cerebral cortex after supplementation with 30 p.p.m. Ph 2 Se 2 . Conversely, no alterations in GSHPx and CAT activities, nor in thiobarbituric acid reactive substances levels were observed in rabbit tissues. These results indicate that oral supplementation with Ph 2 Se 2 is relatively secure in rabbits after 8 months of exposure. The findings encourage further experiments on the potential therapeutic effects of such compound.
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efficacy of 2 3 dimercapto 1 propanesulfonic acid dmps and diphenyl diselenide on cadmium induced testicular damage in mice
Food and Chemical Toxicology, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Paulo Do C Nascimento, Marieli S Marques, Cristina W NogueiraAbstract:Abstract The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl 2 (2.5 or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined, such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) and diphenyl diselenide (PhSe) 2 were studied. The results demonstrated an inhibition of δ-ALA-D activity, a reduction of ascorbic acid and an increase of lipid peroxidation induced by cadmium, indicating testes damage. Furthermore, we observed an increase of plasma LDH, AST and ALT activities. DMPS (400 mol/kg) and (PhSe) 2 (100 μmol/kg) partially protected from the inhibitory effect of 2.5 mg/kg CdCl 2 on δ-ALA-D and from the increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe) 2 therapy was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5 mg/kg. Treatment with DMPS and (PhSe) 2 , individually or combined, was inefficient in reducing cadmium-induced plasma LDH and ALT activity increase. The use of combined therapy (DMPS plus (PhSe) 2 ) proved to be efficient in decreasing cadmium levels in testes and in ameliorating plasma AST activity from animals that received the highest dose of cadmium.
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diphenyl diselenide reverses cadmium induced oxidative damage on mice tissues
Chemico-Biological Interactions, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Simone Nardin Weis, Juliana M Fachinetto, Alexandre M Favero, Cristina W NogueiraAbstract:The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of Toxicological Parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma Parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.
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cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice
Toxicology Letters, 2004Co-Authors: Francielli Weber Santos, João Rocha, Tatiana Oro, Gilson Zeni, Paulo Do C Nascimento, Cristina W NogueiraAbstract:Abstract Acute effects of cadmium in mice testes were evaluated. Animals received a single dose of CdCl2 (2.5 mg/kg or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible protective effect of meso-2,3-dimercaptosuccinic acid (DMSA) and diphenyl diselenide (PhSe)2 are studied. The results demonstrated inhibition of δ-ALA-D and SOD activities, reduction in ascorbic acid, increase of lipid peroxidation induced by cadmium, indicating testes damage. DMSA (400 μmol/Kg) and (PhSe)2 (100 μmol/Kg) protected inhibitory effect of 2.5 mg/kg CdCl2 on δ-ALA-D and restored the increase of TBARS levels. Otherwise, (PhSe)2 treatment was effective in reducing the increase of TBARS levels induced by 5 mg/kg CdCl2, whereas DMSA and (PhSe)2, in combination, were ineffective in reducing TBARS level. However, these compounds alone or in combination, were unable to protect SOD activity and to improve ascorbic acid levels near to the normal value. The use of combined therapy (DMSA plus (PhSe)2) not proved be better than the monotherapy, in improving Toxicological Parameters evaluated in this model of testicular damage induced by cadmium.
Francielli Weber Santos - One of the best experts on this subject based on the ideXlab platform.
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efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice
Toxicology Letters, 2007Co-Authors: Cristiane Luchese, Cristina W Nogueira, Ricardo Brandao, Renata De Oliveira, Francielli Weber SantosAbstract:Abstract This study was designed to examine if diphenyl diselenide (PhSe) 2 , an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl 2 . Male adult Swiss albino mice received CdCl 2 (10 μmol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe) 2 (10 μmol/kg or 20 μmol/kg, orally) was given concomitantly with CdCl 2 to mice. A number of Toxicological Parameters in lung and brain of mice were examined including δ-aminolevulinic acid dehydratase (δ-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na + ,K + -ATPase activity, acetylcholinesterase (AChE) activity, [ 3 H]glutamate uptake and [ 3 H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe) 2 at the dose of 20 μmol/kg protected the inhibition of δ-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl 2 in lungs. At 10 μmol/kg, (PhSe) 2 protected cerebral AChE and CAT activities inhibited by CdCl 2 . There were no histopathological alterations in the lung of mice after CdCl 2 exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl 2 than in control mice. (PhSe) 2 at dose of 20 μmol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe) 2 attenuated the oxidative damage induced by CdCl 2 in lung and brain of mice.
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efficacy of 2 3 dimercapto 1 propanesulfonic acid dmps and diphenyl diselenide on cadmium induced testicular damage in mice
Food and Chemical Toxicology, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Paulo Do C Nascimento, Marieli S Marques, Cristina W NogueiraAbstract:Abstract The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl 2 (2.5 or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined, such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) and diphenyl diselenide (PhSe) 2 were studied. The results demonstrated an inhibition of δ-ALA-D activity, a reduction of ascorbic acid and an increase of lipid peroxidation induced by cadmium, indicating testes damage. Furthermore, we observed an increase of plasma LDH, AST and ALT activities. DMPS (400 mol/kg) and (PhSe) 2 (100 μmol/kg) partially protected from the inhibitory effect of 2.5 mg/kg CdCl 2 on δ-ALA-D and from the increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe) 2 therapy was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5 mg/kg. Treatment with DMPS and (PhSe) 2 , individually or combined, was inefficient in reducing cadmium-induced plasma LDH and ALT activity increase. The use of combined therapy (DMPS plus (PhSe) 2 ) proved to be efficient in decreasing cadmium levels in testes and in ameliorating plasma AST activity from animals that received the highest dose of cadmium.
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diphenyl diselenide reverses cadmium induced oxidative damage on mice tissues
Chemico-Biological Interactions, 2005Co-Authors: Francielli Weber Santos, João Rocha, Gilson Zeni, Simone Nardin Weis, Juliana M Fachinetto, Alexandre M Favero, Cristina W NogueiraAbstract:The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of Toxicological Parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the Parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma Parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.
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cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice
Toxicology Letters, 2004Co-Authors: Francielli Weber Santos, João Rocha, Tatiana Oro, Gilson Zeni, Paulo Do C Nascimento, Cristina W NogueiraAbstract:Abstract Acute effects of cadmium in mice testes were evaluated. Animals received a single dose of CdCl2 (2.5 mg/kg or 5 mg/kg, intraperitoneally) and a number of Toxicological Parameters in mice testes were examined such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible protective effect of meso-2,3-dimercaptosuccinic acid (DMSA) and diphenyl diselenide (PhSe)2 are studied. The results demonstrated inhibition of δ-ALA-D and SOD activities, reduction in ascorbic acid, increase of lipid peroxidation induced by cadmium, indicating testes damage. DMSA (400 μmol/Kg) and (PhSe)2 (100 μmol/Kg) protected inhibitory effect of 2.5 mg/kg CdCl2 on δ-ALA-D and restored the increase of TBARS levels. Otherwise, (PhSe)2 treatment was effective in reducing the increase of TBARS levels induced by 5 mg/kg CdCl2, whereas DMSA and (PhSe)2, in combination, were ineffective in reducing TBARS level. However, these compounds alone or in combination, were unable to protect SOD activity and to improve ascorbic acid levels near to the normal value. The use of combined therapy (DMSA plus (PhSe)2) not proved be better than the monotherapy, in improving Toxicological Parameters evaluated in this model of testicular damage induced by cadmium.
E Cacho - One of the best experts on this subject based on the ideXlab platform.
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mouse bioassay for palytoxin specific symptoms and dose response against dose death time relationships
Food and Chemical Toxicology, 2008Co-Authors: Pilar Riobo, Beatriz Paz, Jose M Franco, Jose Antonio Vazquez, M A Murado, E CachoAbstract:Nowadays, a variety of protocols are applied to quantitate palytoxin. However, there is not desirable agreement among them, the confidence intervals of the basic Toxicological Parameters are too wide and the formal descriptions lack the necessary generality to establish comparisons. Currently, the mouse bioassay is the most accepted one to categorize marine toxins and it must constitute the reference for other methods. In the present work, the mouse bioassay for palytoxin is deeply analyzed and carefully described showing the initial symptoms of injected mice which are presented here in the first time. These symptoms clearly differ from the more common marine toxins described up to now. Regarding to the Toxicological aspects two considerations are taking into account: (i) the empiric models based in the dose-death time relationships cause serious ambiguities and (ii) the traditional moving average method contains in its regular use any inaccuracy elements. Herein is demonstrated that the logistic equation and the accumulative function of Weibull's distribution (with the modifications proposed) generate satisfactory Toxicological descriptions in all the respects.
