Effect of galectin-3 protein inhibition on cisplatin-induced heart toxicity

• Grant number: 21/04139-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2021
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Nycole Morelli Belote
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Galectin-3 (Gal-3) is a ²-galactoside-binding protein that is associated with heart fibrosis due to its positive regulation of the inflammatory response and oxidative stress. However, the cellular and molecular mechanisms involved in the role of Gal-3 in the heart in a cardiotoxicity model are not well determined. Thus, this study will evaluate the effect of pharmacological inhibition of Gal-3 on cisplatin-induced cardiotoxicity in Wistar rats. The animals will be divided into 4 groups (n = 6/group): SHAM - will receive sterile saline via intraperitoneal (i.p.) for 3 days; CIS - will receive via i.p. cisplatin (10 mg/kg/day) for 3 days; SHAM + PEC - will receive modified citrus pectin (Gal-3 inhibitor) orally (100 mg/kg/day) for 7 days, followed by sterile saline i.p. for 3 days; PEC + CIS - will receive modified citrus pectin orally for 7 days followed by i.p. cisplatin for another 3 days. After 6 hours of the last dose of cisplatin or vehicle, animals will be euthanized for the following analyzes: I) quantification of peripheral blood leukocytes; II) histopathology of the heart using hematoxylin-eosin and Gomori trichrome stains; III) expression of Gal-3 and the antioxidant enzyme catalase in the heart by immunohistochemistry; iv) measurement of malondialdehyde in the heart using the thiobarbituric acid method. The results will contribute to a better understanding of the biological role of Gal-3 in cardiotoxicity, as well as possible therapeutic targets to minimize the deleterious effects of cisplatin in combination therapy. (AU)