Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos

Detalhes bibliográficos
Ano de defesa: 2010
Autor(a) principal: Benvegnú, Dalila Moter lattes
Orientador(a): Burger, Marilise Escobar lattes
Banca de defesa: Loro, Vania Lucia lattes, Fachinetto, Roselei lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Programa de Pós-Graduação: Programa de Pós-Graduação em Farmacologia
Departamento: Farmacologia
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufsm.br/handle/1/8974
Resumo: Cyclophosphamide (CP) is an alkylating agent widely used in anticancer and immunosuppression therapy. Like other chemotherapies, this drug can induce damage in healthy tissues, generating multiple organ toxicity. The study of natural substances able to prevent or reduce the toxicity induced by the chemotherapy is very important. Pecan nut shell (Carya illinoensis) is a vegetal by-product with low cost and elevated antioxidant potential and therefore can be considered a promissory substance. The aim of this study was to verify whether the cited antioxidant protects against multiple tissue damage induced by CP. Wistar rats received water or pecan shell aqueous extract (AE - 5%) ad libitum in place of drinking water up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the animals were sacrificed by exsanguination. The blood was collected to obtain plasma and erythrocytes. Vital tissues as heart, liver, kidney, testis and bladder were removed. The occurrence of oxidative stress (OS) was observed through the determination of lipid peroxidation (LP), measured by the thiobarbituric acid reactive substances (TBARS) formation and reduced glutathione (GSH) in all removed tissues, the enzyme catalase (CAT) in the heart, liver, kidney and testis, the enzyme superoxide dismutase (SOD) in the testis and the plasmatic vitamin C (VIT C) levels. Furthermore, the testicular function was evaluated by the enzyme lactate deydrogenase (LDH) and the macroscopic and histopathological analysis of the bladder was carried out. Results demonstrated that the CP treatment increased TBARS and decreased GSH levels in all studied tissues. Moreover, the activities of SOD in the testis and CAT in the heart were increased. However, in the other organs, the activity of the latter was diminished. The testicular LDH and plasmatic VIT C levels were also decreased. Finally, the bladder of the CP treated rats showed dark color and various histological alterations, such as thickening of the lines, hemorrhage, edema, leukocyte infiltration and vascular proliferation. The co-treatment with AE was able to prevent the TBARS increase and GSH depletion in all tissues, except heart and plasma, respectively. The extract also prevented changes in the testicular SOD and CAT activity in all organs, except the kidney. Besides, the extract prevented alteration in plasmatic VIT C and testicular LDH as well as various visual and histological changes in the rat bladder. These findings provided important evidences of the protective effect of pecan shell AE against the general organic toxicity induced by CP. Therefore, this natural substance may be considered to minimize adverse effects related with this chemotherapy, improving the life quality of patients who need to use this type of drug.
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spelling 2013-05-162013-05-162010-01-29BENVEGNÚ, Dalila Moter. ACTION OF Carya illinoensis ON THE CYCLOPHOSPHAMIDE INDUCED TOXICITY IN RATS. 2010. 107 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010.http://repositorio.ufsm.br/handle/1/8974Cyclophosphamide (CP) is an alkylating agent widely used in anticancer and immunosuppression therapy. Like other chemotherapies, this drug can induce damage in healthy tissues, generating multiple organ toxicity. The study of natural substances able to prevent or reduce the toxicity induced by the chemotherapy is very important. Pecan nut shell (Carya illinoensis) is a vegetal by-product with low cost and elevated antioxidant potential and therefore can be considered a promissory substance. The aim of this study was to verify whether the cited antioxidant protects against multiple tissue damage induced by CP. Wistar rats received water or pecan shell aqueous extract (AE - 5%) ad libitum in place of drinking water up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the animals were sacrificed by exsanguination. The blood was collected to obtain plasma and erythrocytes. Vital tissues as heart, liver, kidney, testis and bladder were removed. The occurrence of oxidative stress (OS) was observed through the determination of lipid peroxidation (LP), measured by the thiobarbituric acid reactive substances (TBARS) formation and reduced glutathione (GSH) in all removed tissues, the enzyme catalase (CAT) in the heart, liver, kidney and testis, the enzyme superoxide dismutase (SOD) in the testis and the plasmatic vitamin C (VIT C) levels. Furthermore, the testicular function was evaluated by the enzyme lactate deydrogenase (LDH) and the macroscopic and histopathological analysis of the bladder was carried out. Results demonstrated that the CP treatment increased TBARS and decreased GSH levels in all studied tissues. Moreover, the activities of SOD in the testis and CAT in the heart were increased. However, in the other organs, the activity of the latter was diminished. The testicular LDH and plasmatic VIT C levels were also decreased. Finally, the bladder of the CP treated rats showed dark color and various histological alterations, such as thickening of the lines, hemorrhage, edema, leukocyte infiltration and vascular proliferation. The co-treatment with AE was able to prevent the TBARS increase and GSH depletion in all tissues, except heart and plasma, respectively. The extract also prevented changes in the testicular SOD and CAT activity in all organs, except the kidney. Besides, the extract prevented alteration in plasmatic VIT C and testicular LDH as well as various visual and histological changes in the rat bladder. These findings provided important evidences of the protective effect of pecan shell AE against the general organic toxicity induced by CP. Therefore, this natural substance may be considered to minimize adverse effects related with this chemotherapy, improving the life quality of patients who need to use this type of drug.A ciclofosfamida (CP) é um agente alquilante muito usado na terapia anticâncer e imunossupressora. Assim como outros quimioterápicos, este fármaco pode causar danos aos tecidos saudáveis, gerando toxicidade em múltiplos órgãos. Desta forma, o estudo de substâncias naturais capazes de prevenir ou minimizar a toxicidade decorrente do tratamento quimioterápico vem ganhando sua importância. A casca da noz pecã (Carya illinoensis), é um sub-produto de origem vegetal de baixo custo e com elevado potencial antioxidante, constituindo uma substância promissora. O objetivo deste estudo foi verificar se o extrato aquoso bruto do vegetal citado apresenta efeito protetor contra os danos teciduais múltiplos induzidos pela CP. Ratos Wistar receberam água potável ou extrato aquoso bruto (EAB 5%) da casca da noz pecã, ad libitum, no lugar da água de beber até o final do experimento. No trigésimo dia, a metade de cada grupo recebeu uma administração única de veículo ou CP 200 mg/kg-ip. Após 7 dias, os animais foram sacrificados por exsanguinação, para obtenção de plasma e eritrócitos, enquanto alguns tecidos como coração, fígado, rim, testículos e bexiga foram removidos. Parâmetros de estresse oxidativo (EO) foram avaliados através da peroxidação lipídica (LPO), medida por meio da formação de espécies reativas ao ácido tiobarbitúrico (TBARS) e glutationa reduzida (GSH) em todos os tecidos avaliados, bem como a enzima catalase (CAT) no coração, fígado, rim e testículos. A enzima superóxido dismutase (SOD) testicular e os níveis plasmáticos de vitamina C (VIT C) também foram determinados. A função testicular foi determinada através dos níveis da enzima lactato desidrogenase (LDH). A bexiga foi submetida à avaliação macroscópica e histopatológica, já que é um tecido intensamente danificado pela CP. Os resultados obtidos demonstraram que o tratamento com CP aumentou os níveis de TBARS e diminuiu os níveis de GSH em todos os tecidos avaliados. A atividade da SOD testicular apresentou-se aumentada, bem como a atividade da CAT no coração. Nos demais órgãos, a atividade desta última enzima encontrou-se diminuída. Os níveis da enzima LDH testicular e os níveis plasmáticos de VIT C também se apresentaram reduzidos. Por último, as bexigas dos ratos tratados com CP mostraram coloração escura e diversas alterações histológicas, tais como: espessamento das camadas, hemorragia, edema, infiltração leucocitária e proliferação vascular. O co-tratamento com EAB foi capaz de prevenir o aumento do TBARS e diminuição do GSH em todos os tecidos, exceto coração e plasma, respectivamente. O extrato também preveniu modificações na atividade da SOD testicular e da CAT em todos os órgãos, exceto no rim. Além disso, o extrato também preveniu as alterações nos níveis de VIT C plasmática e LDH testicular, bem como as modificações macroscópicas e histopatológicas na bexiga dos ratos tratados com CP. Os resultados apresentados aqui evidenciam os efeitos protetores do EAB das casca da noz pecã sobre a toxicidade generalizada da CP. Deste modo, este sub-produto da indústria da noz pode ser considerado para minimizar os efeitos indesejáveis relacionados ao tratamento com CP, melhorando a qualidade de vida dos pacientes que necessitam deste quimioterápico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaCiclofosfamidaCarya illinoensisNoz pecãEstresse oxidativoAntioxidanteCyclophosphamideCarya illinoensisPecan nutOxidative stressAntioxidantCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAAção protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratosAction of Carya illinoensis on the cyclophosphamide induced toxicity in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBurger, Marilise Escobarhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6Loro, Vania Luciahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4796333D7Fachinetto, Roseleihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2http://lattes.cnpq.br/6134516963963514Benvegnú, Dalila Moter201000000000400500500500500cea6b067-f9a7-4654-8ec5-65f1c465c1a843333e59-8522-4f68-a863-ba9dd29b55be2e9b2b2b-1d72-4976-bf48-be44ffcb83726a615e4f-285a-4d77-aeb6-a33cd9c07f80info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdfDissertação de Mestradoapplication/pdf772670http://repositorio.ufsm.br/bitstream/1/8974/1/DIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdfdf59f2e03a1c3625467b0fd7923d4ed7MD51TEXTBENVEGNU, DALILA MOTER.pdf.txtBENVEGNU, DALILA MOTER.pdf.txtExtracted texttext/plain155636http://repositorio.ufsm.br/bitstream/1/8974/2/BENVEGNU%2c%20DALILA%20MOTER.pdf.txte2d9719dd77854e799d95e2f4b539230MD52DIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.txtDIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.txtExtracted texttext/plain155636http://repositorio.ufsm.br/bitstream/1/8974/4/DIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.txte2d9719dd77854e799d95e2f4b539230MD54THUMBNAILBENVEGNU, DALILA MOTER.pdf.jpgBENVEGNU, DALILA MOTER.pdf.jpgIM Thumbnailimage/jpeg5148http://repositorio.ufsm.br/bitstream/1/8974/3/BENVEGNU%2c%20DALILA%20MOTER.pdf.jpg2778da48bc3b4a74b9fd51d469a750bdMD53DIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.jpgDIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.jpgIM Thumbnailimage/jpeg5148http://repositorio.ufsm.br/bitstream/1/8974/5/DIS_PPGFARMACOLOGIA_2010_BENVEGNU_DALILA.pdf.jpg2778da48bc3b4a74b9fd51d469a750bdMD551/89742020-05-09 03:01:37.563oai:repositorio.ufsm.br:1/8974Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132020-05-09T06:01:37Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.por.fl_str_mv Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
dc.title.alternative.eng.fl_str_mv Action of Carya illinoensis on the cyclophosphamide induced toxicity in rats
title Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
spellingShingle Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
Benvegnú, Dalila Moter
Ciclofosfamida
Carya illinoensis
Noz pecã
Estresse oxidativo
Antioxidante
Cyclophosphamide
Carya illinoensis
Pecan nut
Oxidative stress
Antioxidant
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
title_full Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
title_fullStr Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
title_full_unstemmed Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
title_sort Ação protetora da Carya illinoensis sobre a toxicidade induzida por ciclofosfamida em ratos
author Benvegnú, Dalila Moter
author_facet Benvegnú, Dalila Moter
author_role author
dc.contributor.advisor1.fl_str_mv Burger, Marilise Escobar
dc.contributor.advisor1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6
dc.contributor.referee1.fl_str_mv Loro, Vania Lucia
dc.contributor.referee1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4796333D7
dc.contributor.referee2.fl_str_mv Fachinetto, Roselei
dc.contributor.referee2Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6134516963963514
dc.contributor.author.fl_str_mv Benvegnú, Dalila Moter
contributor_str_mv Burger, Marilise Escobar
Loro, Vania Lucia
Fachinetto, Roselei
dc.subject.por.fl_str_mv Ciclofosfamida
Carya illinoensis
Noz pecã
Estresse oxidativo
Antioxidante
topic Ciclofosfamida
Carya illinoensis
Noz pecã
Estresse oxidativo
Antioxidante
Cyclophosphamide
Carya illinoensis
Pecan nut
Oxidative stress
Antioxidant
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
dc.subject.eng.fl_str_mv Cyclophosphamide
Carya illinoensis
Pecan nut
Oxidative stress
Antioxidant
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Cyclophosphamide (CP) is an alkylating agent widely used in anticancer and immunosuppression therapy. Like other chemotherapies, this drug can induce damage in healthy tissues, generating multiple organ toxicity. The study of natural substances able to prevent or reduce the toxicity induced by the chemotherapy is very important. Pecan nut shell (Carya illinoensis) is a vegetal by-product with low cost and elevated antioxidant potential and therefore can be considered a promissory substance. The aim of this study was to verify whether the cited antioxidant protects against multiple tissue damage induced by CP. Wistar rats received water or pecan shell aqueous extract (AE - 5%) ad libitum in place of drinking water up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the animals were sacrificed by exsanguination. The blood was collected to obtain plasma and erythrocytes. Vital tissues as heart, liver, kidney, testis and bladder were removed. The occurrence of oxidative stress (OS) was observed through the determination of lipid peroxidation (LP), measured by the thiobarbituric acid reactive substances (TBARS) formation and reduced glutathione (GSH) in all removed tissues, the enzyme catalase (CAT) in the heart, liver, kidney and testis, the enzyme superoxide dismutase (SOD) in the testis and the plasmatic vitamin C (VIT C) levels. Furthermore, the testicular function was evaluated by the enzyme lactate deydrogenase (LDH) and the macroscopic and histopathological analysis of the bladder was carried out. Results demonstrated that the CP treatment increased TBARS and decreased GSH levels in all studied tissues. Moreover, the activities of SOD in the testis and CAT in the heart were increased. However, in the other organs, the activity of the latter was diminished. The testicular LDH and plasmatic VIT C levels were also decreased. Finally, the bladder of the CP treated rats showed dark color and various histological alterations, such as thickening of the lines, hemorrhage, edema, leukocyte infiltration and vascular proliferation. The co-treatment with AE was able to prevent the TBARS increase and GSH depletion in all tissues, except heart and plasma, respectively. The extract also prevented changes in the testicular SOD and CAT activity in all organs, except the kidney. Besides, the extract prevented alteration in plasmatic VIT C and testicular LDH as well as various visual and histological changes in the rat bladder. These findings provided important evidences of the protective effect of pecan shell AE against the general organic toxicity induced by CP. Therefore, this natural substance may be considered to minimize adverse effects related with this chemotherapy, improving the life quality of patients who need to use this type of drug.
publishDate 2010
dc.date.issued.fl_str_mv 2010-01-29
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dc.identifier.citation.fl_str_mv BENVEGNÚ, Dalila Moter. ACTION OF Carya illinoensis ON THE CYCLOPHOSPHAMIDE INDUCED TOXICITY IN RATS. 2010. 107 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010.
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/8974
identifier_str_mv BENVEGNÚ, Dalila Moter. ACTION OF Carya illinoensis ON THE CYCLOPHOSPHAMIDE INDUCED TOXICITY IN RATS. 2010. 107 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010.
url http://repositorio.ufsm.br/handle/1/8974
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