Galectin-3 is a key hepatoprotective molecule against the deleterious effect of cisplatin

Author(s)

Santos, Diego D. ; Sasso, Gisela R. S. ; Belote, Nycole M. ; da Silva, Rafael Andre ; Lice, Izabella ; Correia-Silva, Rebeca D. ; Borges, Fernanda T. ; Carbonel, Adriana A. F. ; Gil, Cristiane D.

• Document type: Journal article
• Source: Life Sciences; v. 318, p. 10-pg., 2023-02-17.

Abstract

Aims: Evaluate the role of galectin-3 in the liver using an acute model of cisplatin-induced toxicity. Material and methods: Modified citrus pectin (MCP) treatment was used to inhibit galectin-3. Rats were distrib-uted into four groups: SHAM, CIS, MCP and MCP + CIS. On days 1-7, animals were treated by oral gavage with 100 mg/kg/day of MCP (MCP and MCP + CIS groups). On days 8, 9 and 10, animals received intraperitoneal injection of 10 mg/kg/day of cisplatin (CIS and MCP + CIS groups) or saline (SHAM and MCP groups). Key findings: Cisplatin administration caused a marked increase in hepatic leukocyte influx and liver degenera-tion, and promoted reactive oxygen species production and STAT3 activation in hepatocytes. Plasma levels of cytokines (IL-6, IL-10), and hepatic toxicity biomarkers (hepatic arginase 1, alpha-glutathione S-transferase, sorbitol dehydrogenase) were also elevated. Decreased galectin-3 levels in the livers of animals in the MCP + CIS group were also associated with increased hepatic levels of malondialdehyde and mitochondrial respiratory complex I. Animals in the MCP + CIS group also exhibited increased plasma levels of IL-1 beta, TNF-alpha, and aspartate trans-aminase 1. Furthermore, MCP therapy efficiently antagonized hepatic galectin-9 in liver, but not galectin-1, the latter of which was increased. Significance: Reduction of the endogenous levels of galectin-3 in hepatocytes favors the process of cell death and increases oxidative stress in the acute model of cisplatin-induced toxicity. (AU)

• FAPESP's process: 20/03565-2 - Effect of annexin A1 and its mimetic peptides in models of inflammatory response in vitro (2D and 3D) and acute toxicity in vivo
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants