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

Abstract

AimsEvaluate the role of galectin-3 in the liver using an acute model of cisplatin-induced toxicity. Material and methodsModified citrus pectin (MCP) treatment was used to inhibit galectin-3. Rats were distributed 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 findingsCisplatin administration caused a marked increase in hepatic leukocyte influx and liver degeneration, 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, α-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-1β, TNF-α, and aspartate transaminase 1. Furthermore, MCP therapy efficiently antagonized hepatic galectin-9 in liver, but not galectin-1, the latter of which was increased. SignificanceReduction 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.