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

• Autor(a) principal: Santos, Diego D. [UNESP]
• Data de Publicação: 2023
• Outros Autores: Sasso, Gisela R.S., Belote, Nycole M., da Silva, Rafael André [UNESP], Lice, Izabella, Correia-Silva, Rebeca D., Borges, Fernanda T., Carbonel, Adriana A.F., Gil, Cristiane D. [UNESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.lfs.2023.121505; http://hdl.handle.net/11449/246849
• topic: Hepatotoxicity; Inflammation; Lipid peroxidation; Mitochondria; Modified citrus pectin; Reactive oxygen species

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 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 findings: Cisplatin 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. 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.