An Inhibitor of Cell Proliferation Associated with Adhesion Formation Is Suppressed by N,O-Carboxymethyl Chitosan

Abstract

Surgical adhesions are a major cause of morbidity and mortality. The ideal barrier agent will both minimize adhesions and provide a milieu for the regeneration of the mesothelium lining of the abdominal and thoracic cavities. N,O-Carboxymethylchitosan (NOCC), a derivation of chitin that markedly reduces adhesions, may function to modulate intracellular signals such as growth factors and cytokines in the inflammatory exudate. Since transforming growth factor-β is implicated in the fibrotic process, we investigated the possibility that NOCC's effects on adhesion formation reflects a modulation of TGF-β activity. Using a biological assay for inhibition of cell proliferation to detect TGF-β activity, we demonstrate that NOCC suppresses the levels of an inhibitor of cell proliferation released into serum and peritoneal exudates after ce-cal abrasion in the rat. However, this activity was distinct from known forms of TGF-β as determined using both TGF-β-neutralizing antisera and a TGF-β-resistant cell proliferation assay. Thus at least one potential effect of NOCC involves a mechanism distinct from TGF-β inhibition.

Key Words:

• adhesions
• animals
• N,O-carboxymethyl chitosan
• prevention
• surgery
• transforming growth factor beta