Prevention of cyclophosphamide-induced hemorrhagic cystitis by glucose-mannose binding plant lectins

Abstract

Purpose: Neutrophils are implicated in the physiopathologic alterations of hemorrhagic cystitis (HC). Thus, we decided to test the antiinflammatory activity of glucose-mannose binding lectins extracted from D. violacea and D. guianensis seeds, which showed an inhibitory effect upon neutrophil migration in a model of rat peritonitis based on HC experimentally induced by cyclophosphamide (CYP).

Materials and methods: Mice were treated with mesna (40 mg./kg., i.p.), lectins (1 and 10 mg./kg., i.v.) and 0.1 M of alpha-D-methyl-mannoside (alpha-CH3) or alpha-D-galactose (alpha-D-gal). The HC was induced by CYP (200 mg./kg., i.p.). The results were evaluated 12 hours after HC induction, based on the following parameters: vesical edema measurements, macroscopic and microscopic analysis of the bladders (Gray's analysis). The vesical edema was quantified either by the increase in bladder wet weight or by the determination of vesical vascular permeability (Evans' blue leakage).

Results: CYP-induced vesical edema was prevented by mesna and lectin treatment. The lectin effects were dose-dependent, and at the highest dose were similar to that achieved by mesna treatment. alpha-CH3 selectively reversed the lectin inhibitory effect. Histopathological analysis corroborated these findings and showed an intense reduction of leukocyte infiltration and tissue damage by lectin treatment. The bladders from the mesna-treated group showed a nearly normal histological pattern. However, differently from this group, none of the lectins abolished CYP-induced hemorrhage.

Conclusions: The glucose-mannose binding lectins showed strong antiinflammatory activity in the mouse model of HC induced by CYP. As lectins mainly affected leukocyte vesical infiltration, we suggest a competitive blockage of glucosylated (mannose-glucose) selectin binding sites by lectins.