Vitamin C attenuation of the development of type I diabetes mellitus by interferon-alpha.
Interferon alpha (IFN-alpha) inhibits insulin release and may be cytotoxic to pancreatic islets. Increased free radical activity may be implicated in the cytotoxic action of IFN-alpha 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-alpha, as well as the possible protective effect of two antioxidants, vitamin C and mannitol. Compared to untreated rats, it was shown that IFN-alpha 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 lipids 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-alpha treatment. Plasma glucagon was increased after 2 weeks. Administration of vitamin C along with IFN-alpha succeeded in modulating most of the altered parameters affected during IFN-alpha. The hyperglycaemic effect of IFN-alpha 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-alpha caused no changes in the parameters studied compared to that induced by treatment with IFN-alpha alone.
Department of Pharmacology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
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al-Zuhair
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Mohamed
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016898:Interferon-alpha / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D051381:Rats
D000975:Antioxidants; D005609:Free Radicals; D007328:Insulin; D016898:Interferon-alpha; D008353:Mannitol; D001205:Ascorbic Acid