VITAMIN-C ATTENUATION OF THE DEVELOPMENT OF TYPE-I DIABETES-MELLITUS BY INTERFERON-ALPHA

Interferon alpha (IFN-alpha) inhibits insulin release and may be cytot oxic to pancreatic islets. Increased free radical activity may be impl icated in the cytotoxic action of IFN-alpha and development of diabete s mellitus. Therefore we measured markers of free radical activity (li pid peroxides and the non-peroxide-conjugated diene isomer of linoleic acid [PL-9,11-LA']) along with some pancreatic variables in male albi no rats treated with IFN-alpha, as well as the possible protective eff ect of two antioxidants, vitamin C and mannitol. Compared to untreated rats, it was shown that IFN-alpha induced an increase in plasma gluco se. Pancreatic and serum insulin, as well as serum C-peptide, were inc reased after 1 week, then their levels were reduced after 2 weeks. Pla sma lipid peroxides and (PL-9,11-LA') were markedly elevated, while li noleic acid was reduced. These changes in the studied parameters were attributed, in part, to the superoxide and free radical generation dur ing IFN-alpha treatment. Plasma glucagon was increased after 2 weeks. Administration of vitamin C along with IFN-alpha succeeded in modulati ng most of the altered parameters affected during IFN-alpha. The hyper glycaemic effect of IFN-alpha was greatly ameliorated and the negative effect on pancreatic and serum insulin and serum C-peptide were nearl y abolished. The elevated levels of lipid peroxide and (PL-9,11-LA') a nd the reduction in linoleic acid being normalised. The only persisten t effect was the increase in plasma glucagon. Concurrent administratio n of mannitol with IFN-alpha caused no changes in the parameters studi ed compared to that induced by treatment with IFN-alpha alone. (C) 199 8 The Italian Pharmacological Society.