EFFECT OF LONG-TERM TREATMENT WITH A PURIFIED MICRONIZED FLAVONOID FRACTION ON PANCREATIC MONONUCLEAR CELL INFILTRATION IN DIABETIC BB RATS

Bio Breeding (BB) rats develop a genetically determined insulin-depend ent diabetes, because of the early destruction of pancreatic beta cell s of Langerhans islets, massively infiltrated by inflammatory mononucl ear cells. S 5682, registered as Daflon, 500 mg, is a purified microni zed flavonoid fraction (90% diosmin, 10% hesperidin), which has been s hown to possess antiinflammatory properties, including anti-free radic al activity, effects on vascular permeability, venous tone, and perive nous inflammation. We studied the effect of S 5682 on the course of pa ncreatic insulitis in diabetic BE rats. All the diabetic BE rats were hyperglycemic, with an increase of plasma levels of fructosamine, alph a-1 acid glycoprotein, and fibrinogen, and a dramatic decrease of C-pe ptide level. These parameters were not modified by S 5682. Pancreas hi stologic studies showed that in S 5682-treated diabetic BE rats, lymph ocytic infiltration of Langerhans islets was less important and freque nt than in untreated diabetic BE rats. By quantitative analysis, a hig hly significant difference was observed for insulitis, as well as peri vasculitis, between S 5682-treated and untreated diabetic BE rats. Thi s inhibitory effect of S 5682 on pancreatic mononuclear cell infiltrat ion may be useful for a complementary treatment to decrease the develo pment of insulitis in human insulin-dependent diabetes mellitus.