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 inhibitor of lipid peroxidation, U-83836-E (a derivative of vitamin E), in order 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 they were killed after 21 days. Results revealed that there was a significant increase in glycaemia in treated groups up to day 14 after which no further increase was noticed. Superoxide dismutase (SOD) assay showed that: (1) the LDS treatment significantly reduces SOD activity when compared with untreated controls (P < 0.005); (2) U-83836-E increases SOD levels (when compared with untreated controls); and (3) U-83836-E counteracts LDS treatment, since SOD activity is significantly higher with respect to that found in LDS-controls (P < 0.05), and SOD levels were significantly higher with respect to that found in Group 2 animals (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 controls than in the other groups and the lowest values were found in U-83836-E controls and in normoglycaemic animals treated with both streptozocin and U-83836-E. Morphological observations demonstrated that islet β cells were of normal appearance in normoglycaemic animals of the treated groups. In conclusion, the in vivo inhibition of lipid peroxidation by this compound produces a limited but significant prevention of the islet β cell destruction. © 1995.