Pamidronate in the prevention of acute doxorubicin-induced cardiotoxicity

• Grant number: 13/04280-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2013
• End date: October 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bertha Furlan Polegato
• Grantee: Paula Bernardo de Carvalho
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Doxorubicin (DOX) is a drug used in the treatment of malignancies, but cardiotoxicity is the major side effect, which can be initiated immediately after drug´s infusion. Mechanisms involved in the genesis of the injury are increased inflammatory activity and activation of matrix metalloproteinases (MMP). Interventions which minimize activation of MMPs may play a role in cardiotoxicity's prevention. Pamidronate (PMD) is used in diseases that alter bone metabolism, such as osteoporosis. However, there are many others biological effects of this drug, such as inflammatory response reduction and decrease MMP activation. Therefore, the aim of the study is evaluating the effect of PMD in DOX-induced acute cardiotoxicity in rats. For this, rats will receive intraperitoneal injection of PMD (3mg/kg) and DOX (20mg/kg). We will have four experimental groups: DOX-PMD, PMD-control, DOX-control and control-control. Animals will be euthanized 48 hours following the infusion of drugs. In vivo cardiac function analysis will be performed by echocardiography and in vitro functional analysis will be performed by isolated heart study. The heart is collected for histological analysis, measurement of IL-10, IFN-gamma, TNF-alpha and ICAM-1 by ELISA and analysis of MMP activity 2 and 9 by zymography. Statistical analysis will be performed by two-way ANOVA. The significance level will be considered 5%.