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Doctoral Thesis
DOI
10.11606/T.7.2013.tde-12092014-121109
Document
Author
Full name
Cassiane Dezoti da Fonseca
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Vattimo, Maria de Fatima Fernandes (President)
Borges, Fernanda Teixeira
Magro, Marcia Cristina da Silva
Neiva, Luciana Barros de Moura
Watanabe, Mirian
Title in Portuguese
Nefropatia induzida por contraste iodado e o diabetes mellitus: modelo experimental em ratos
Keywords in Portuguese
Contraste (efeito adverso)
Diabetes Mellitus
Estresse Oxidativo
Insuficiência Renal Aguda
Abstract in Portuguese
A nefropatia induzida por contraste (NIC) é uma lesão renal aguda (LRA) tóxica, que consiste em vasoconstrição intra-renal, toxicidade tubular direta com liberação de espécies reativas de oxigênio (EROs). A NIC está diretamente associada a doenças crônicas que comprometem a oxigenação da região da medula renal, como a disfunção renal preexistente, o Diabetes Mellitus (DM) e insuficiência cardíaca congestiva. Esse estudo investigou os mecanismos fisiopatológicos que caracterizam a NIC em ratos diabéticos. Foram utilizados ratos Wistar, adultos e machos. No protocolo DM foi realizada a nefrectomia unilateral esquerda (Nefré) no 1º dia, para potencializar o efeito tóxico da hiperglicemia crônica no rim. O DM foi induzido pela administração intravenosa (i.v.) de 65 mg/kg de estreptozotocina (STZ, diluída com citrato) no 20º dia, e o contraste iodado (CI) ioxitalamato de meglumina, 6 ml/kg, foi administrado (intraperitoneal, i.p.) no 85º dia. Foram realizados os seguintes grupos: Citrato (controle); Nefré+Citrato; DM; Nefré+DM; DM+CI; Nefré+DM+CI. Foram avaliados parâmetros fisiológicos (ingestão de ração e água, peso, glicemia capilar, peso do rim e peso relativo do rim); a albuminúria (método de imunodifusão), a função renal (FR) (clearance de creatinina, método de Jaffé), a lesão oxidativa (peróxidos urinários-PU, FOX-2; substâncias reativas com o ácido tiobarbitúrico-TBARS, tióis no tecido renal) e análise histológica renal (lesão tubulointersticial). Observou-se que os grupos diabéticos apresentaram polifagia, polidipsia, hiperglicemia e redução do peso corporal (p<0,05), além de redução do clearance de creatinina com elevação de PU e TBARS, manutenção de tióis e elevação da albuminúria. O tratamento com CI nos animais diabéticos determinou redução da FR, elevação dos PU e TBARS e redução dos tióis. Quanto à histologia renal, demonstrou-se que apenas o grupo Nefré+DM+CI apresentou lesão tubulointersticial. Os achados dessa investigação confirmaram o efeito tóxico do CI dose única sobre a função renal de ratos com hiperglicemia crônica, pressupondo que o DM seja fator de risco para essa nefropatia.
Title in English
Iodine contrast-induced nephropathy and diabetes mellitus: experimental model in rats.
Keywords in English
Acute Renal Failure
Contrast (adverse effect)
Diabetes Mellitus
Oxidative Stress
Abstract in English
Contrast-Induced Nephropathy (CIN) is a toxic acute kidney injury (AKI) that consists in intrarenal vasoconstriction, direct tubular toxicity with generation of reactive oxygen species (ROS). The CIN is associated with the decreased tissue oxygen tension in renal medula in preexisting renal dysfunction, Diabetes Mellitus (DM) and congestive heart failure. This study investigated the pathophysiologic mechanisms in the CIN in diabetic rats. Adult, male, Wistar rats were used. It was performed left uninephrectomy (Nx) on the 1st day in the DM group to potentialize the toxic effect of the chronic hyperglycemia. The DM was induced by a single dose of intravenous streptozotocin (65mg/kg i.v.) in sodium citrate buffer, on the 20th day and the iodine contrast (IC) meglumine ioxithalamate 6 ml/kg was administrated (intraperitoneal, i.p.) on the 85th day. Animals were divided into the following groups: Citrate (control); Nx+Citrate; DM; Nx+DM; DM+IC; Nx+DM+IC. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight and relative kidney weight); renal function (creatinine clearance, Jaffé method); urine albumin (imunodifusion method); oxidative injury (urinary peroxides, FOX-2, tiobarbituric acid reactive substances-TBARS and thiols in renal tissue) and kidney histological analysis (tubulointerstitial injury) were evaluated. In the diabetic groups, polyphagia, polydipsia, increased blood glucose and reduced body weight were observed (p<0.05). The relative kidney weight was increased in the Nx and IC animals (p<0.05). The renal function was reduced; urinary peroxides and TBARS were increased in the diabetic and IC animals. The decrease in thiols levels in the diabetic and IC groups demonstrated the endogenous substrate consumption. The Nx animals that received IC presented tubular cells vacuolization and edema with moderate injury. The data has described the pathophysiology of CIN in diabetic rats involving oxidative injury that resulted of association of chronic high blood glucose and IC toxicity, suggesting that DM can be pointed out as a risk factor for CIN.
 
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Publishing Date
2014-09-18
 
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