AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B

Detalhes bibliográficos
Autor(a) principal: VONCIK, KETLLYN SIMONE
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do UNICENTRO
Texto Completo: http://tede.unicentro.br:8080/jspui/handle/jspui/663
Resumo: Amphotericin B is a macrolide antibiotic used against systemic fungal infections and leishmaniasis. Due to the increasing number of immunocompromised patients and resistance to antimicrobial drugs Amphotericin is in focus, even though the drug discovery in 1955 has been used effectively with little fungal resistance. The drug has hepatic, hematologic and renal toxicity, and its use is often necessary to discontinue. Curcumin is a natural pigment that has been used in conjunction with nephrotoxic and hepatotoxic drugs, mitigating their effects. Three experiment that aimed to determine the dose and timing of administration of Amphotericin B nephrotoxicity, hepato-and hematotoxicity and check the action of Curcumin on the toxicity of the drug were performed in addition to the possible changes caused by the use of curcumin in the biochemical, hematological and histopathological parameters. The initial experiment was a curve of dose and time of administration of Amphotericin B ( 20 mg/kg/10 days , 40 mg/kg/10 days , 80 mg/kg/10 days , 20 mg/kg/30 days , 40 mg / kg/30 days, n = 6 ) to determine the toxic dose . The second experiment consisted in the application of Amphotericin B intravenously (3 mg / kg) and oral administration of Curcumin (100 mg / kg) for 5 days (n=8). The third experiment involved the intravenous administration of Amphotericin B deoxycholate (1 mg / kg) and curcumin (100 mg / kg ) for 5 days (n = 10). To check hematological changes of animals were performed. Renal function was assessed by measurement of urea and serum creatinine and liver function by quantifying the ALT and alkaline phosphatase. Histopathological examination of kidneys and livers of animals were performed. The results were expressed as mean and standard deviation and the adopted significance level of 5 %. Were employed statistic test Shapiro -Wilk and Levene test for homogeneity of variances of the groups. For variables that did not violate the assumption of homogeneity was employed one-way ANOVA and post hoc Bonferroni and the variables who violated was used the nonparametric test Kruskal- Wallis with a significance value correction for multiple comparisons, followed by test Dunnet. In Curve dose changes occurred in hematological parameters, compared to the control groups in 40 mg/kg/10 days and 80 mg/kg/10 days. In the second experiment, Amphotericin B group of all groups differed with respect to urea. In the third experiment infusion reactions were observed in animals in which it was applied to Amphotericin B deoxycholate, occurring death in 50 % of animals treated with Amphotericin B deoxycholate and 30% treated concomitantly with amphotericin B deoxycholate and Curcumin. There are indications of protective pigment on acute drug reactions, however this experiment we observed changes in hematological parameters (hematocrit, hemoglobin and number of red blood cells) in animals treated with amphotericin B deoxycholate and Curcumin / curcumin when compared with those of group control, a fact that was not observed in the previous experiment. So it has not been possible to check liver and kidney toxicity of Amphotericin B and the protective action of curcumin. It can be stated that curcumin did not cause hepatic and renal changes as well as weight of the animals. This new form studies should be conducted to verify the activity of Curcumin on infusion reactions of Amphotericin B deoxycholate and possible hematological changes caused by natural compound.
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spelling BONINI, JULIANA SARTORIhttp://lattes.cnpq.br/7239838542231670044.209.419-10http://lattes.cnpq.br/8970555387721940VONCIK, KETLLYN SIMONE2017-06-05T16:48:27Z2014-02-21VONCIK, KETLLYN SIMONE. AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B. 2014. 78 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR.http://tede.unicentro.br:8080/jspui/handle/jspui/663Amphotericin B is a macrolide antibiotic used against systemic fungal infections and leishmaniasis. Due to the increasing number of immunocompromised patients and resistance to antimicrobial drugs Amphotericin is in focus, even though the drug discovery in 1955 has been used effectively with little fungal resistance. The drug has hepatic, hematologic and renal toxicity, and its use is often necessary to discontinue. Curcumin is a natural pigment that has been used in conjunction with nephrotoxic and hepatotoxic drugs, mitigating their effects. Three experiment that aimed to determine the dose and timing of administration of Amphotericin B nephrotoxicity, hepato-and hematotoxicity and check the action of Curcumin on the toxicity of the drug were performed in addition to the possible changes caused by the use of curcumin in the biochemical, hematological and histopathological parameters. The initial experiment was a curve of dose and time of administration of Amphotericin B ( 20 mg/kg/10 days , 40 mg/kg/10 days , 80 mg/kg/10 days , 20 mg/kg/30 days , 40 mg / kg/30 days, n = 6 ) to determine the toxic dose . The second experiment consisted in the application of Amphotericin B intravenously (3 mg / kg) and oral administration of Curcumin (100 mg / kg) for 5 days (n=8). The third experiment involved the intravenous administration of Amphotericin B deoxycholate (1 mg / kg) and curcumin (100 mg / kg ) for 5 days (n = 10). To check hematological changes of animals were performed. Renal function was assessed by measurement of urea and serum creatinine and liver function by quantifying the ALT and alkaline phosphatase. Histopathological examination of kidneys and livers of animals were performed. The results were expressed as mean and standard deviation and the adopted significance level of 5 %. Were employed statistic test Shapiro -Wilk and Levene test for homogeneity of variances of the groups. For variables that did not violate the assumption of homogeneity was employed one-way ANOVA and post hoc Bonferroni and the variables who violated was used the nonparametric test Kruskal- Wallis with a significance value correction for multiple comparisons, followed by test Dunnet. In Curve dose changes occurred in hematological parameters, compared to the control groups in 40 mg/kg/10 days and 80 mg/kg/10 days. In the second experiment, Amphotericin B group of all groups differed with respect to urea. In the third experiment infusion reactions were observed in animals in which it was applied to Amphotericin B deoxycholate, occurring death in 50 % of animals treated with Amphotericin B deoxycholate and 30% treated concomitantly with amphotericin B deoxycholate and Curcumin. There are indications of protective pigment on acute drug reactions, however this experiment we observed changes in hematological parameters (hematocrit, hemoglobin and number of red blood cells) in animals treated with amphotericin B deoxycholate and Curcumin / curcumin when compared with those of group control, a fact that was not observed in the previous experiment. So it has not been possible to check liver and kidney toxicity of Amphotericin B and the protective action of curcumin. It can be stated that curcumin did not cause hepatic and renal changes as well as weight of the animals. This new form studies should be conducted to verify the activity of Curcumin on infusion reactions of Amphotericin B deoxycholate and possible hematological changes caused by natural compound.A Anfotericina B é um antibiótico macrolídeo utilizado contra infecções fúngicas sistêmicas e leishmaniose. Devido ao aumento no número de pacientes imunossuprimidos e da resistência aos fármacos antimicrobianos a Anfotericina está em foco, apesar de descoberta em 1955 a droga tem sido usada com eficácia e com pouca resistência fúngica. A droga pode apresenta toxicidade hepática, hematológica e renal, sendo necessário muitas vezes descontinuar seu uso. A Curcumina é um pigmento natural que já foi utilizado em conjunto com drogas nefrotóxicas e hepátotóxicas, amenizando seus efeitos. Foram realizados três experimento que tinham como objetivo determinar a dose e o tempo de administração da Anfotericina B que causam nefro, hepato e hematotoxicidade, bem como verificar a ação da Curcumina sobre a toxicidade da droga, além das possíveis alterações causadas pelo uso da Curcumina nos parâmetros bioquímicos, hematológicos e histopatológicos. O experimento inicial foi uma Curva de dose e tempo de administração de Anfotericina B (20 mg/kg/10 dias, 40 mg/kg/10 dias, 80 mg/kg/10 dias, 20 mg/kg/30 dias, 40 mg/kg/30 dias, n=6) para averiguar a dose tóxica. O segundo experimento consistiu na aplicação de Anfotericina B intravenosa (3 mg/kg) e administração de Curcumina via oral (100 mg/kg) por 5 dias (n=8). O terceiro experimento consistiu na administração intravenosa de Anfotericina B desoxicolato (1 mg/kg) e Curcumina (100 mg/kg) por 5 dias (n=10). Para verificar alterações hematológicas foram realizados hemograma dos animais. A função renal foi avaliada através da mensuração da uréia e creatinina sérica e a hepática pela quantificação da ALT e fosfatase alcalina. Foi realizado exame histopatológico dos rins e fígados dos animais. Os resultados obtidos foram descritos em média e desvio padrão e adotado o nível de significância de 5%. Foram empregados os testes estatísticos Shapiro-Wilk e teste de Levene para homogeneidade das variâncias dos grupos. Para as variáveis que não violaram o pressuposto de homogeneidade foi empregado o teste ANOVA one way com post hoc de Bonferroni e para as que violaram foi empregado o teste não paramétrico de Kruskal-Wallis com correção do valor de significância para múltiplas comparações, seguido de teste de Dunnet. Na Curva de dose ocorreram alterações hematológicas, em relação ao controle nos grupos 40 mg/kg/10 dias e 80 mg/kg/10 dias. No segundo experimento, grupo Anfotericina B diferiu de todos os grupos em relação a uréia. No terceiro experimento foram observadas reações infusionais nos animais em que foi aplicada a Anfotericina B desoxicolato, ocorrendo a morte de 50% dos animais tratados com Anfotericina B desoxicolato e 30% dos tratados concomitantemente com Anfotericina B desoxicolato e Curcumina, além de ser observada perda de peso nos animais do grupo Anfotericina e Anfotericina/Curcumina. Há indícios de proteção do pigmento sobre as reações agudas do fármaco, entretanto nesse experimento observaram-se alterações nos parâmetros hematológicos (hematócrito, hemoglobina e número de hemácias) nos animais tratados com Curcumina e Anfotericina B desoxicolato/Curcumina quando comparados com os animais do grupo controle, fato que não foi observado no experimento anterior. Assim não foi possível verificar a toxicidade hepática e renal da Anfotericina B, bem como a ação protetora da Curcumina. Pode-se afirmar que a Curcumina não provocou alterações hepáticas e renais, bem como no peso dos animais. Dessa forma novos estudos devem ser realizados para verificar a atividade da Curcumina sobre as reações infusionais da Anfotericina B desoxicolato e possíveis alterações hematológicas causadas pelo composto natural.Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2017-06-05T16:48:27Z No. of bitstreams: 1 KETLLYN SIMONE VONCIK.pdf: 5165636 bytes, checksum: d35f9a14d5e21d67984da334d4688c5b (MD5)Made available in DSpace on 2017-06-05T16:48:27Z (GMT). No. of bitstreams: 1 KETLLYN SIMONE VONCIK.pdf: 5165636 bytes, checksum: d35f9a14d5e21d67984da334d4688c5b (MD5) Previous issue date: 2014-02-21Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede.unicentro.br:8080/jspui/retrieve/2014/KETLLYN%20SIMONE%20VONCIK.pdf.jpgporUniversidade Estadual do Centro-OestePrograma de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG)UNICENTROBrasilUnicentro::Departamento de Ciências da SaúdeAnfotericina BCurcuminatoxicidadeantifúngicoAmphotericin BcurcumintoxicityantifungalCIENCIAS DA SAUDE::FARMACIAAVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA Binfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-7679163762264962259600600600600-693476683800971729069976364134497549962075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UNICENTROinstname:Universidade Estadual do Centro-Oeste (UNICENTRO)instacron:UNICENTROLICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/jspui/663/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51ORIGINALKETLLYN SIMONE VONCIK.pdfKETLLYN SIMONE VONCIK.pdfapplication/pdf5165636http://localhost:8080/tede/bitstream/jspui/663/2/KETLLYN+SIMONE+VONCIK.pdfd35f9a14d5e21d67984da334d4688c5bMD52TEXTKETLLYN SIMONE VONCIK.pdf.txtKETLLYN SIMONE VONCIK.pdf.txttext/plain132980http://localhost:8080/tede/bitstream/jspui/663/3/KETLLYN+SIMONE+VONCIK.pdf.txtb7aa270a54bca62f39252beb33d0d5dbMD53THUMBNAILKETLLYN SIMONE VONCIK.pdf.jpgKETLLYN SIMONE VONCIK.pdf.jpgimage/jpeg1943http://localhost:8080/tede/bitstream/jspui/663/4/KETLLYN+SIMONE+VONCIK.pdf.jpgcc73c4c239a4c332d642ba1e7c7a9fb2MD54jspui/6632017-09-12 15:06:16.136oai:localhost:jspui/663Biblioteca Digital de Teses e Dissertaçõeshttp://tede.unicentro.br:8080/jspui/PUBhttp://tede.unicentro.br/tde_oai/oai3.phprepositorio@unicentro.br||fabianoqueiroz@yahoo.com.bropendoar:2017-09-12T18:06:16Biblioteca Digital de Teses e Dissertações do UNICENTRO - Universidade Estadual do Centro-Oeste (UNICENTRO)false
dc.title.por.fl_str_mv AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
title AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
spellingShingle AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
VONCIK, KETLLYN SIMONE
Anfotericina B
Curcumina
toxicidade
antifúngico
Amphotericin B
curcumin
toxicity
antifungal
CIENCIAS DA SAUDE::FARMACIA
title_short AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
title_full AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
title_fullStr AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
title_full_unstemmed AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
title_sort AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B
author VONCIK, KETLLYN SIMONE
author_facet VONCIK, KETLLYN SIMONE
author_role author
dc.contributor.advisor1.fl_str_mv BONINI, JULIANA SARTORI
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7239838542231670
dc.contributor.authorID.fl_str_mv 044.209.419-10
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8970555387721940
dc.contributor.author.fl_str_mv VONCIK, KETLLYN SIMONE
contributor_str_mv BONINI, JULIANA SARTORI
dc.subject.por.fl_str_mv Anfotericina B
Curcumina
toxicidade
antifúngico
topic Anfotericina B
Curcumina
toxicidade
antifúngico
Amphotericin B
curcumin
toxicity
antifungal
CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Amphotericin B
curcumin
toxicity
antifungal
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description Amphotericin B is a macrolide antibiotic used against systemic fungal infections and leishmaniasis. Due to the increasing number of immunocompromised patients and resistance to antimicrobial drugs Amphotericin is in focus, even though the drug discovery in 1955 has been used effectively with little fungal resistance. The drug has hepatic, hematologic and renal toxicity, and its use is often necessary to discontinue. Curcumin is a natural pigment that has been used in conjunction with nephrotoxic and hepatotoxic drugs, mitigating their effects. Three experiment that aimed to determine the dose and timing of administration of Amphotericin B nephrotoxicity, hepato-and hematotoxicity and check the action of Curcumin on the toxicity of the drug were performed in addition to the possible changes caused by the use of curcumin in the biochemical, hematological and histopathological parameters. The initial experiment was a curve of dose and time of administration of Amphotericin B ( 20 mg/kg/10 days , 40 mg/kg/10 days , 80 mg/kg/10 days , 20 mg/kg/30 days , 40 mg / kg/30 days, n = 6 ) to determine the toxic dose . The second experiment consisted in the application of Amphotericin B intravenously (3 mg / kg) and oral administration of Curcumin (100 mg / kg) for 5 days (n=8). The third experiment involved the intravenous administration of Amphotericin B deoxycholate (1 mg / kg) and curcumin (100 mg / kg ) for 5 days (n = 10). To check hematological changes of animals were performed. Renal function was assessed by measurement of urea and serum creatinine and liver function by quantifying the ALT and alkaline phosphatase. Histopathological examination of kidneys and livers of animals were performed. The results were expressed as mean and standard deviation and the adopted significance level of 5 %. Were employed statistic test Shapiro -Wilk and Levene test for homogeneity of variances of the groups. For variables that did not violate the assumption of homogeneity was employed one-way ANOVA and post hoc Bonferroni and the variables who violated was used the nonparametric test Kruskal- Wallis with a significance value correction for multiple comparisons, followed by test Dunnet. In Curve dose changes occurred in hematological parameters, compared to the control groups in 40 mg/kg/10 days and 80 mg/kg/10 days. In the second experiment, Amphotericin B group of all groups differed with respect to urea. In the third experiment infusion reactions were observed in animals in which it was applied to Amphotericin B deoxycholate, occurring death in 50 % of animals treated with Amphotericin B deoxycholate and 30% treated concomitantly with amphotericin B deoxycholate and Curcumin. There are indications of protective pigment on acute drug reactions, however this experiment we observed changes in hematological parameters (hematocrit, hemoglobin and number of red blood cells) in animals treated with amphotericin B deoxycholate and Curcumin / curcumin when compared with those of group control, a fact that was not observed in the previous experiment. So it has not been possible to check liver and kidney toxicity of Amphotericin B and the protective action of curcumin. It can be stated that curcumin did not cause hepatic and renal changes as well as weight of the animals. This new form studies should be conducted to verify the activity of Curcumin on infusion reactions of Amphotericin B deoxycholate and possible hematological changes caused by natural compound.
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identifier_str_mv VONCIK, KETLLYN SIMONE. AVALIAÇÃO DO EFEITO DA CURCUMINA SOBRE A TOXICIDADE DA ANFOTERICINA B. 2014. 78 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas - Mestrado / Associação Ampla com UEPG) - Universidade Estadual do Centro-Oeste, Guarapuava - PR.
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