THE VITAMIN-E DERIVATIVE U-X3836-E IN THE LOW-DOSE STREPTOZOCIN-TREATED MOUSE - EFFECTS ON DIABETES DEVELOPMENT

Low-dose streptozocin-treated (LDS) mice were administered an inhibito r of lipid peroxidation, U-83X36-E (a derivative of vitamin E), in ord er to observe its ability to alter the onset of diabetes. Ten or 20 mg /kg body wt. per day of U-83836-E were given to mice for 7 days and th ey were killed after 21 days. Results revealed that there was a signif icant increase in glycaemia in treated groups up to day 14 after which no further increase was noticed. Superoxide dismutase (SOD) assay sho wed that: (1) the LDS treatment significantly reduces SOD activity whe n compared with untreated controls (P < 0.005); (2) U-83836-E increase s SOD levels (when compared with untreated controls); and (3) U-83836- E counteracts LDS treatment, since SOD activity is significantly highe r with respect to that found in LDS-controls (P < 0.05), and SOD level s were significantly higher with respect to that found in Group 2 anim als (P < 0.05), but significantly lower with respect to those found in groups 3 and 4 (P < 0.005). Moreover, malondialdehyde (MDA), the end- product of lipoperoxidation, was found at much higher levels in LDS co ntrols than in the other groups and the lowest values were found in U- 83836-E controls and in normoglycaemic animals treated with both strep tozocin and U-83836-E. Morphological observations demonstrated that is let beta cells were of normal appearance in normoglycaemic animals of the treated groups. In conclusion, the in vivo inhibition of lipid per oxidation by this compound produces a limited but significant preventi on of the islet beta cell destruction.