ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 216, No. 1, June, pp. 204-212, 1982 Effects of Vitamin E, Ascorbic Acid and Mannitol on Alloxan-Induced Lipid Peroxidation in Rats’ C. J. DILLARD, K. J. KUNERT, AND A. L. TAPPEL2 Dqxwhmt of Food Science and Technobgg, University of Cah&rnia, Davis, California 95616 Received November 30,1981, and in revised form January 27,1982 w6- and w&unsaturated lipid hydroperoxides decompose to yield pentane and ethane, respectively. Alloxan toxicity was studied in rats in relation to pentane and ethane produced during lipid peroxidation induced by intraperitoneal injection of 20 mg of alloxan/lOO g body wt. Fifteen minutes after injection, vitamin E-deficient rats exhaled 102- and Il.&fold more pentane and ethane, respectively, than prior to injection. In- jection of 75 mg ascorbic acid/100 g body wt 30 min prior to alloxan treatment prolonged the time over which peroxidation occurred, and all vitamin E-deficient rats died before 4 h. Vitamin E-deficient rats injected with 100 mg of the radical scavenger mannitol/ 100 g body wt 30 min prior to alloxan treatment were completely protected against lipid peroxidation, and none of the rats died by 4 h. Rats fed 40 iu dl-a-tocopherol acetate/kg diet or injected with 100 mg dZ-a-tocopherol/lOOg body wt were either totally protected against alloxan and alloxan-ascorbic acid-induced peroxidation or were only slightly affected as shown by very low-level pentane and ethane production. Thiobarbituric acid reactants in plasma, liver, and pancreas 4 h after alloxan treatment reflected the prooxidant nature of ascorbic acid and alloxan, the vitamin E status of the rats, and the protective effect of mannitol. Plasma glucose levels 4 h after alloxan injection were lowest in vitamin E-injected rats and highest in vitamin E-deficient rats. Only in vitamin E-deficient rats were both lipid peroxidation and significantly elevated plasma glucose levels observed by 4 h post-alloxan treatment. Alloxan is a potent oxidizing agent that has been used since about 1943 to produce diabetes in animals (1). Tremendous sci- entific efforts have been made to reveal the basic mechanism by which alloxan produces diabetes. In general, the mech- anism of the overall toxic nature of this compound to the whole animal has not been emphasized. A recent paper (2) dis- cusses the radical chemistry of the qui- none-hydroquinone cycle of the alloxan- 1 This investigation was supported by United States Public Health Service Research Grant AM-09933 from the National Institute of Arthritis, Metabolism and Digestive Diseases. K.J.K. was a recipient of a grant from the De&ache Forschungsgemeinschaft. *Author to whom all correspondence should be addressed. dialuric acid pair. This paper and others point out the involvement of hydrogen peroxide and oxygen-free radicals in the chemistry of alloxan reactions. Heikkila and co-workers (3-5) proposed that hy- droxyl radicals can mediate diabetes. The possible involvement of hydroxyl radicals in alloxan-induced diabetes has been sup- ported by studies that show hydroxyl rad- ical scavengers protect animals against diabetes (6) and protect isolated pan- creatic cells from damage in vitro (7-9). However, it is not possible to say with cer- tainty that hydroxyl radicals are defi- nitely involved in cytotoxicity of alloxan because the specificity of some of the rad- ical scavengers used for the hydroxyl rad- ical is questionable. 0003-9861/82/070204-09$XI2.00/0 204 Copyright Q 1982 by Academic Press, Inc. All rlgbta of reproduction in any form reaervd.