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Silma Regina Ferreira Pereira - One of the best experts on this subject based on the ideXlab platform.
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Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Luís Cláudio Lima De Jesus, Rossy-eric Pereira Soares, Vanessa Ribeiro Moreira, Raissa Lacerda Pontes, Patrícia Valéria Castelo-branco, Silma Regina Ferreira PereiraAbstract:Meglumine Antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that Meglumine Antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by Meglumine Antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg Meglumine Antimoniate via intraperitoneal (i.p.) route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg Meglumine Antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving Meglumine Antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine Antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with Meglumine Antimoniate.
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Meglumine Antimoniate glucantime causes oxidative stress derived dna damage in balb c mice infected by leishmania leishmania infantum
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum
Antimicrobial agents and chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Soy isoflavones have antimutagenic activity on DNA damage induced by the antileishmanial Glucantime (Meglumine Antimoniate)
Drug and chemical toxicology, 2014Co-Authors: Ludymila Furtado Cantanhêde, Laís Pinheiro Almeida, Rossy-eric Pereira Soares, Patrícia Valéria Castelo Branco, Silma Regina Ferreira PereiraAbstract:Isoflavones are phytoestrogens reported to be potent antioxidant agents. In contrast, the antileishmanial Meglumine Antimoniate has mutagenic activities. This study evaluated the ability of soy isoflavones to reduce DNA damage induced by Meglumine Antimoniate. Antimutagenic effects (by micronucleus test) were tested using Swiss mice divided into seven groups treated with Meglumine Antimoniate (425 mg/kg bw pentavalent antimony); cyclophosphamide (50 mg/kg bw); water (negative control); single isoflavones dose (1.6 mg/kg bw), and three groups received one dose of isoflavones via gavage (0.4 mg/kg bw, 0.8 mg/kg bw or 1.6 mg/kg bw) plus Meglumine Antimoniate via intraperitoneal, simultaneously. To evaluate antigenotoxicity (by Comet assay), each group with 10 animals received the above-mentioned control doses; single dose of isoflavones 0.8 mg/kg bw, and three groups received isoflavones (0.8 mg/kg bw) by gavage along with intraperitoneal Meglumine Antimoniate, which were treated with isoflavones 24 h before or after receiving Meglumine Antimoniate (pre-treatment and post-treatment, respectively) or simultaneously. Cells were harvested 24 h after the treatment, and the data were evaluated by ANOVA followed by Tukey's test (p
Vanessa Ribeiro Moreira - One of the best experts on this subject based on the ideXlab platform.
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Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Luís Cláudio Lima De Jesus, Rossy-eric Pereira Soares, Vanessa Ribeiro Moreira, Raissa Lacerda Pontes, Patrícia Valéria Castelo-branco, Silma Regina Ferreira PereiraAbstract:Meglumine Antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that Meglumine Antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by Meglumine Antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg Meglumine Antimoniate via intraperitoneal (i.p.) route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg Meglumine Antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving Meglumine Antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine Antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with Meglumine Antimoniate.
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Meglumine Antimoniate glucantime causes oxidative stress derived dna damage in balb c mice infected by leishmania leishmania infantum
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum
Antimicrobial agents and chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
Luís Cláudio Lima De Jesus - One of the best experts on this subject based on the ideXlab platform.
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Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Luís Cláudio Lima De Jesus, Rossy-eric Pereira Soares, Vanessa Ribeiro Moreira, Raissa Lacerda Pontes, Patrícia Valéria Castelo-branco, Silma Regina Ferreira PereiraAbstract:Meglumine Antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that Meglumine Antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by Meglumine Antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg Meglumine Antimoniate via intraperitoneal (i.p.) route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg Meglumine Antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving Meglumine Antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine Antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with Meglumine Antimoniate.
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Meglumine Antimoniate glucantime causes oxidative stress derived dna damage in balb c mice infected by leishmania leishmania infantum
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum
Antimicrobial agents and chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
Rossy-eric Pereira Soares - One of the best experts on this subject based on the ideXlab platform.
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Genistein and Ascorbic Acid Reduce Oxidative Stress-Derived DNA Damage Induced by the Antileishmanial Meglumine Antimoniate.
Antimicrobial agents and chemotherapy, 2018Co-Authors: Luís Cláudio Lima De Jesus, Rossy-eric Pereira Soares, Vanessa Ribeiro Moreira, Raissa Lacerda Pontes, Patrícia Valéria Castelo-branco, Silma Regina Ferreira PereiraAbstract:Meglumine Antimoniate (Glucantime) is a pentavalent antimonial used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that Meglumine Antimoniate causes oxidative stress-derived DNA damage. Knowing that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by Meglumine Antimoniate. For that, mice (n = 5/group) received genistein (via gavage) in doses of 5, 10, and 20 mg/kg for three consecutive days. After this period, they were treated with 810 mg/kg Meglumine Antimoniate via intraperitoneal (i.p.) route. Furthermore, mice (n = 5/group) simultaneously received ascorbic acid (i.p.) in doses of 30, 60, and 120 mg/kg and 810 mg/kg Meglumine Antimoniate. We also conducted post- and pretreatment assays, in which animals received ascorbic acid (60 mg/kg) 24 h prior to or after receiving Meglumine Antimoniate. Genomic instability and mutagenicity were analyzed through conventional comet assay and enzymatic assay using formamide pyrimidine DNA glycosylase (Fpg) enzyme, as well as the micronucleus test, respectively. Meglumine Antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid was capable of reducing mutagenic effects in simultaneous treatment as well as in posttreatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with Meglumine Antimoniate.
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Meglumine Antimoniate glucantime causes oxidative stress derived dna damage in balb c mice infected by leishmania leishmania infantum
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum
Antimicrobial agents and chemotherapy, 2017Co-Authors: Vanessa Ribeiro Moreira, Rossy-eric Pereira Soares, Luís Cláudio Lima De Jesus, Luis Douglas Miranda Silva, Bruno Araújo Serra Pinto, Maria Norma Melo, Antonio Marcus De Andrade Paes, Silma Regina Ferreira PereiraAbstract:Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine Antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which Meglumine Antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with Meglumine Antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that Meglumine Antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both Meglumine Antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a Meglumine Antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment.
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Soy isoflavones have antimutagenic activity on DNA damage induced by the antileishmanial Glucantime (Meglumine Antimoniate)
Drug and chemical toxicology, 2014Co-Authors: Ludymila Furtado Cantanhêde, Laís Pinheiro Almeida, Rossy-eric Pereira Soares, Patrícia Valéria Castelo Branco, Silma Regina Ferreira PereiraAbstract:Isoflavones are phytoestrogens reported to be potent antioxidant agents. In contrast, the antileishmanial Meglumine Antimoniate has mutagenic activities. This study evaluated the ability of soy isoflavones to reduce DNA damage induced by Meglumine Antimoniate. Antimutagenic effects (by micronucleus test) were tested using Swiss mice divided into seven groups treated with Meglumine Antimoniate (425 mg/kg bw pentavalent antimony); cyclophosphamide (50 mg/kg bw); water (negative control); single isoflavones dose (1.6 mg/kg bw), and three groups received one dose of isoflavones via gavage (0.4 mg/kg bw, 0.8 mg/kg bw or 1.6 mg/kg bw) plus Meglumine Antimoniate via intraperitoneal, simultaneously. To evaluate antigenotoxicity (by Comet assay), each group with 10 animals received the above-mentioned control doses; single dose of isoflavones 0.8 mg/kg bw, and three groups received isoflavones (0.8 mg/kg bw) by gavage along with intraperitoneal Meglumine Antimoniate, which were treated with isoflavones 24 h before or after receiving Meglumine Antimoniate (pre-treatment and post-treatment, respectively) or simultaneously. Cells were harvested 24 h after the treatment, and the data were evaluated by ANOVA followed by Tukey's test (p
Rogelio López-vélez - One of the best experts on this subject based on the ideXlab platform.
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Amphotericin B lipid complex versus Meglumine Antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV: a randomized pilot study
The Journal of antimicrobial chemotherapy, 2003Co-Authors: Fernando Laguna, Julián Torre-cisneros, Sebastián Videla, Manuel E. Jiménez-mejías, Guillem Sirera, Esteban Ribera, Dolores Prados, Bonaventura Clotet, Mariano Sust, Rogelio López-vélezAbstract:Optimal treatment for HIV-related visceral leishmaniasis (VL) has still to be established. A pilot clinical trial was carried out in 57 HIV-VL coinfected patients to compare the efficacy and safety of amphotericin B lipid complex (ABLC) versus Meglumine Antimoniate. The patients were randomized to receive either ABLC 3 mg/kg/day for 5 days (ABLC-5, 18 patients), ABLC 3 mg/kg/day for 10 days (ABLC-10, 20 patients) or Meglumine Antimoniate 20 mg Sbv /kg/day for 28 days (19 patients). Treatment was considered successful if parasites were not detected in a bone marrow aspirate after treatment. Parasitological cure was attained in 33% (95% CI: 13%-59%) of the ABLC-5 group, in 42% (95% CI: 16%-62%) of the ABLC-10 group and in 37% (95% CI: 16%-62%) of the Meglumine Antimoniate group (P = 0.94). Eight out of 19 patients administered Antimoniate discontinued treatment prematurely following serious adverse events, compared with one in the ABLC groups (P = 0.0006). The efficacy of ABLC is similar to Meglumine Antimoniate, but the severity of toxicity in the treatment of HIV-VL is lower with ABLC.
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Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing Meglumine Antimoniate with amphotericin B
AIDS (London England), 1999Co-Authors: Fernando Laguna, Rogelio López-vélez, Federico Pulido, Salas A, Julián Torre-cisneros, Torres E, F. J. Medrano, José Sanz, Picó G, Gómez-rodrigo JAbstract:BACKGROUND Visceral leishmaniasis is common in patients with HIV infection living in endemic areas, but the most effective and safe treatment remains unknown. OBJECTIVE To compare the efficacy and safety of Meglumine Antimoniate versus amphotericin B in HIV-infected patients with first episodes of visceral leishmaniasis (VL). DESIGN An open, multicentre, prospective and randomized trial. SETTING Twelve tertiary hospitals. PATIENTS Eighty-nine consecutive HIV-infected patients diagnosed with VL. Patients were randomly assigned to treatment with either Meglumine Antimoniate (20 mg pentavalent antimony per kilogram of body weight per day) or amphotericin B (0.7 mg/kg per day) both for 28 days. Treatment was considered successful if a bone marrow aspirate performed 1 month after the end of therapy did not detect parasites. Relapse was defined as the reappearance of parasites after an initial cure. RESULTS An initial cure was attained in 29 of 44 patients (65.9%) randomly assigned to treatment with Meglumine Antimoniate and 28 of 45 (62.2%) randomly assigned to treatment with amphotericin B. The incidence of moderate to severe adverse events was similar in both groups. The patients treated with Meglumine Antimoniate had higher incidences of cardiotoxicity (14 versus 0%, P = 0.02) and chemical pancreatitis (30 versus 0%, P < 0.01). However, in the amphotericin B group, nephrotoxicity was more frequent (36 versus 5%, P < 0.01). There was no difference in survival or relapse-free interval according to the allocated group of therapy. CONCLUSION Treatment of VL with Meglumine Antimoniate or amphotericin B was shown to have similar efficacy and toxicity rates in Spanish HIV-infected patients. The differences in the toxicity patterns could be useful in choosing one of these agents as first-line treatment.
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Assessment of allopurinol plus Meglumine Antimoniate in the treatment of visceral leishmaniasis in patients infected with HIV
The Journal of infection, 1994Co-Authors: Fernando Laguna, Rogelio López-vélez, Vicente Soriano, Pedro Montilla, Jorge Alvar, Juan González-lahozAbstract:Summary We report on 11 patients with HIV infection and visceral leishmaniasis and who were treated with Meglumine Antimoniate plus allopurinol for 3 weeks (six patients) or 4 weeks (five patients). Clinical and parasitological cures were achieved in four of the five patients treated for 4 weeks and in one of the six patients treated for 3 weeks. Only one patient developed a severe maculopapular rash. Allopurinol plus Meglumine Antimoniate was found to be a safe combination of drugs for the treatment of visceral leishmaniasis in patients infected with HIV. The optimal length of this treatment is unknown but a course of at least 4 weeks' duration would appear to be necessary for obtaining parasitological cure in most cases.