Evaluation of polysucrose 15000 as a marker of intestinal permeability

Abstract

Polysucrose (PS) is a synthetic copolymer of sucrose and epichlorohydrin, which can be produced in a variety of molecular sizes. The aim of the study was to evaluate the functionality of PS 15000, mean mol wt 14700, as a marker for intestinal permeability to macro molecules. In human tests, PS 15000, sometimes together with 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) and 14C-mannitol, was given orally and the renally excreted portion of the markers was quantified. An enzyme immunoassay for PS 15000 was developed for the measuring of PS excretion in urine. PS was shown to be fairly resistant to bacterial degradation. Intravenous injection of PS 15000 revealed rapid renal clearance. Oral PS 15000 challenge in healthy volunteers gave the highest excretion values in the 0-4 h sample followed by a gradual decline, the total excretion being about 0.02% over 12 hours.

Rheumatoid arthritis (RA) patients on non-steroidal anti-inflammatory drug (NSAID) treatment had a twofold increased PS 15000 excretion; initially untreated RA patients with normal PS 15000 test rose in excretion values after one week of NSAID treatment, indicating increased intestinal permeability as a consequence of the treatment rather than being an RA attribute. Patients with Crohn's disease had a significantly increased PS 15000 excretion for the intervals 4-8 h and 8-12 h; permeability was more increased in small-intestinal than in colonic disease, and more increased in active than in quiescent disease. In healthy controls 7 tested on four occasions, PS 15000 was compared to the paracellular marker 5ICr-EDTA and to the transcellular marker 14C-mannitol under different test conditions. PS 15000 excretion values were strongly correlated to those of 5ICr-EDTA, with no correlation to those of 14C-mannitol. PS 15000 and 51Cr-EDTA were not affected by a hyperosmolar test solution but showed increased excretion after one week of NSAID pretreatment, whereas 14C-mannitol excretion was markedly reduced by the hyperosmolar test solution but was not affected by NSAID pretreatment.

In a continued study on the healthy controls a standardised liquid meal increased the number of time intervals with a significant NSAID-induced change in excretion for both PS 15000 and 51Cr-EDTA, i.e. tended to improve the disease vs. health discrimination ability of the tests. Calculation of paracellular/transcellular excretion ratios was not beneficial. Finally, tight junction function or endocytosis were modulated in rat ileal mucosa mounted in Ussing chambers and the effect on the permeability to PS 15000 and 51Cr-EDTA was evaluated. Modulation affected both markers in a similar way, indicating that PS 15000, despite its size, behaves as a marker of paracellular intestinal permeability. PS 15000 seems to fulfil many criteria for an ideal marker of paracellular intestinal permeability.