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

Abstract

Interferon alpha (IFN-α) inhibits insulin release and may be cytotoxic to pancreatic islets. Increased free radical activity may be implicated in the cytotoxic action of IFN-α and development of diabetes mellitus. Therefore we measured markers of free radical activity (lipid peroxides and the non-peroxide-conjugated diene isomer of linoleic acid [PL-9,11-LA′]) along with some pancreatic variables in male albino rats treated with IFN-α, as well as the possible protective effect of two antioxidants, vitamin C and mannitol. Compared to untreated rats, it was shown that IFN-α induced an increase in plasma glucose. Pancreatic and serum insulin, as well as serum C-peptide, were increased after 1 week, then their levels were reduced after 2 weeks. Plasma lipid peroxides and (PL-9,11-LA′) were markedly elevated, while linoleic acid was reduced. These changes in the studied parameters were attributed, in part, to the superoxide and free radical generation during IFN-α treatment. Plasma glucagon was increased after 2 weeks. Administration of vitamin C along with IFN-α succeeded in modulating most of the altered parameters affected during IFN-α. The hyperglycaemic effect of IFN-α was greatly ameliorated and the negative effect on pancreatic and serum insulin and serum C-peptide were nearly abolished. The elevated levels of lipid peroxide and (PL-9,11-LA′) and the reduction in linoleic acid being normalised. The only persistent effect was the increase in plasma glucagon. Concurrent administration of mannitol with IFN-α caused no changes in the parameters studied compared to that induced by treatment with IFN-α alone.