EFFECT OF MODIFIED CITRUS PECTIN ON SPLENIC RESPONSE IN EXPERIMENTAL MODEL OF ACUTE TOXICITY INDUCED BY CISPLATIN

Abstract

Citrus pectin is a complex polysaccharide, derived from citrus fruit peels, which can be modified through a specific pH and enzymatic treatment that makes it low molecular weight and easily absorbed in the intestine. Modified citrus pectin (MCP) produces pleiotropic effects, including anti-proliferative, anti-metastatic, and immunomodulatory effects. MCP also antagonizes the effects of the protein galectin (Gal)-3, demonstrating benefits in preclinical and clinical models. Studies conducted by our group using a cisplatin-induced rodent model of acute toxicity show that MCP not only reduces Gal-3 levels, but also regulates Gal-1 and Gal-9 in the liver. Thus, in this study we will evaluate the effect of MCP on splenic toxicity induced by cisplatin in Wistar rats. The animals will be divided into 4 groups (n = 5): SHAM - will receive sterile saline via intraperitoneal injection; MCP - receive orally 100 mg/kg/day of MCP for 7 days, followed by 3 more days of sterile saline i.p.; CIS - receive via i.p. 10 mg/kg/day of cisplatin for 3 days; MCP+CIS - will receive MCP for 7 days followed by cisplatin via i.p. for another 3 days. Six hours after the last dose of cisplatin or vehicle, the rats will be euthanized for spleen collection and processing for the following analyses: I) spleen histology; II) analysis and quantification of macrophages; III) possible changes in the expression of galectins (-1, -3 and -9) by immunohistochemistry and western blotting. In the publicly available transcriptomes of the Gene Expression Omnibus (GEO) repository, we will evaluate the transcriptional levels of LGALS1, LGALS3 and LGALS9 using studies involving splenic response to different cytotoxic drugs. The results will contribute to a better understanding of the immunomodulatory effects of MCP in the cisplatin-induced splenotoxicity model, as well as its effects on the modulation of galectin levels.