Glucose-induced inhibition of angiogenesis in the rat sponge granuloma is prevented by aminoguanidine

Abstract

Angiogenesis and granulation tissue formation that occur following subcutaneous implantation of sponge implants in nondiabetic rats were inhibited by topical administration of D-glucose (22 mM). The healing impairment induced by glucose was analogous to healing failures associated with diabetes. Angiogenesis has been determined by measuring hemoglobin content in the implants, correlated with histological evidence of cellular infiltration and granulation tissue formation. The amount of hemoglobin detected in the glucose-treated implants was significantly lower (0.06+/-0.005 g/dl) than the amount in the controls that received glucose 5 mM (0.12+/-0.012 g/dl), saline (0.10+/-0.006 g/dl) or mannitol (0.086+/-0.007 g/dl). Parallel histological studies corroborated the biochemical findings. Daily intraperitoneal injection of aminoguanidine (AG, 50 mg/kg) prevented glucose-induced inhibition of neovascularization and cellular infiltration in the sponge granuloma. Our results show the direct inhibitory effect of high glucose in the development of granulation tissue and indicate that it may be associated with nonenzymatic glycation of key components of the healing process in the rat sponge granuloma.