Introduction: Modified citrus pectin (MCP) exhibits diverse biological activities, including anti-proliferative, anti-metastatic, and immunomodulatory effects. Additionally, MCP acts as an antagonist of galectin-3 (Gal-3), a key regulator of inflammation. This study aimed to investigate MCP's therapeutic potential in a murine colitis model induced using dextran sulfate sodium (DSS), focusing on its impact on inflammation and disease severity. Methods: Male C57BL/6 mice were divided into four groups: a control; DSS (colitis induced through the oral administration of 1.25% DSS in water for 7 days ad libitum); MCP (administered via orogastric gavage for 7 days at 100 mg/kg/day); and MCP+DSS. C57BL/6 Gal-3^-/- mice were divided into two groups: control and DSS groups. All of the procedures were approved by the Ethics Committee in Animal Experimentation of UNIFESP (CEUA nº4973090123).

Results: The DSS-treated mice presented significant weight loss on the eighth day and elevated disease activity index scores compared to their respective controls (p<0.0001). The DSS and MCP+DSS animals showed significant shortening of the intestines compared to the controls (p<0.0001), with increased production of IL-17 and TNF-α. A lack of Gal-3 abolished these effects, showing no changes in gut length or these cytokines between the control and DSS groups. Systemically, the spleens of the Gal-3^-/- DSS and MCP+DSS animals were longer than those of the DSS group (p<0.01). However, the plasma KC levels increased significantly in the DSS and MCP+DSS groups; again, the lack of Gal-3 abolished these differences between the DSS and control groups.

Conclusion: MCP therapy as a preventive treatment in the development of DSS-induced colitis was not effective. On the other hand, the lack of endogenous Gal-3 mitigates the deleterious effects of SSD-induced colitis, possibly by preventing an increase in IL-17 and TNF-α. Funding: CAPES, CNPq, and FAPESP.