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

Autor: Santos DD; Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP 15054-000, Brazil., Sasso GRS; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil., Belote NM; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil., da Silva RA; Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP 15054-000, Brazil., Lice I; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil., Correia-Silva RD; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil., Borges FT; Department of Medicine, Nephrology Division, Universidade Federal de São Paulo (UNIFESP), Sao Paulo, SP 04038-901, Brazil., Carbonel AAF; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil., Gil CD; Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP 15054-000, Brazil; Structural and Functional Biology Graduate Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-900, Brazil. Electronic address: cristiane.gil@unifesp.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Apr 01; Vol. 318, pp. 121505. Date of Electronic Publication: 2023 Feb 16.
DOI: 10.1016/j.lfs.2023.121505
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE