Archives of Medical Research Volume 25, No. 3, pp. 377-380, 1994 Printed in Mexico Original Article Pancreatic Lipid Peroxidation in Alloxan-Induced Diabetes Mellitus CLAUDIA SOTO, PABLO MURIEL and JOSE L. REYES Departamento de Sisternas Biolbgicos UAM-X, Departamento de Farmacologia y Toxicologia and Departamento de Fisiologia y Biofisica, CINVESTAV-IPN, MPxico, D.F. Received for publication October 25, 1993; accepted February 2, 1994 (931314). Abstract The time-course of pancreatic lipid peroxidation and reduced glutathione, and blood glucose were studied in adult male CD-1 mice after each of three sequential injections of alloxan, administered at intervals of 48 h. Twenty four hours after alloxan administration an increment of blood glucose and pancreatic lipoperoxidation was observed. Lipo- peroxidation partially recovered, while blood glu- cose was increased after the third administration to a value of 150 mgl100 ml. Pancreas reduced glu- Introduction In experimental animals alloxan diabetes presents several similarities to diabetes mellitus type I in man, with typical symptoms such as body weight loss, polydipsia, polyuria, glycosuria, ketonuria, hyper- glycemia and ketonemia (1). Several hypotheses have been put forward but none of them fully explains the diabetogenic effect of alloxan. Some of the hypotheses include reaction with sulfhydrylgroups, chelating action and enzymatic or metabolic alterations. There is also evidence that alloxan interacts with several of the mechanisms of ionic transport of the cell membrane (2), such as calcium and sodium (3,4). Comespondenceto: Claudio Soto, Departamentode Fisiologia y Biofisica, CINVESTAV- IPN, Aptdo. Postal 14-740, 07000 Mtxico, D.F. Tel: (5) 754-0200, Ext. 5410; FAX: (5) 586-2792 & 586-6290 tathione content remained without any significant change throughout the experiment. These results suggest that the establishment of alloxan-induced diabetes is preceded by an increment in pancreatic lipid peroxidation that could be associated with permanent damage to pancreatic tissue. (Arch Med Res 1994; 29377) KEY WORDS: Glucose; Insulin; Membrane transport; Hyperglycemia; Free radicals. It has been suggested that the diabetogenic action of alloxanincludes the production of highly reactive oxygen- containing radical formed in a redox reaction between this substance and its reduction product, dialuric acid. Such oxygen-containing species as superoxide ion, hydrogen peroxide and hydroxyl radical, which are cytotoxic to the insulin-producing B- cells of the pancreas (6) have been detected in oxygenatedsolutionscontaining alloxan and dialuric acid (5) and in biological systems (7). This suggestion is based on the observation that pretreatment with radical scavengers (8 -11) prevents alloxan-induced diabetes. On the basis of these considerations, we decided to study pancreatic lipid peroxidation and glutathionechanges during the onset of alloxan diabetes and to correlate it with the development of hyperglycemia. Materials and Methods Materials. All chemicals and reagents were supplied by Sigma Chemical Co. (St. Louis, MO, USA). 377