The ulcer healing effect of protamine sulphate in rat stomach.

Abstract

Protamine sulphate has been reported to stimulate nitric oxide production from blood vessels, which is a pivotal factor for gastric ulcer healing. Our preliminary study also showed that protamine sulphate potentiated the ulcer healing effect of heparin. Male SD rats with acetic acid-induced gastric ulcers were given protamine sulphate (40-80 mg/kg, s.c.) twice daily for 4 or 7 days. L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), an inhibitor of nitric oxide synthase (NOS), was given s.c. prior to protamine sulphate (80 mg/kg) treatment. Ulcer healing, angiogenesis, mucosal histological changes, NOS activity and growth factors were determined. Protamine sulphate dose-dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in angiogenesis, mucosal regeneration and constitutive NOS activity. Inhibition of gastric secretion was observed. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha (TNF-alpha) or inducible NOS activity was also affected. L-NAME completely blocked the beneficial effects of protamine sulphate. Protamine sulphate accelerates gastric ulcer healing through a mucosal nitric oxide-dependent and possibly also the EGF-and bFGF-associated pathways, which are followed by an increase of angiogenesis and mucosal regeneration. Acid inhibition contributes in part to the ulcer healing action of protamine sulphate.