ANTIOXIDANT MDL 29,311 PREVENTS DIABETES IN NONOBESE DIABETIC AND MULTIPLE LOW-DOSE STZ-INJECTED MICE

Recent investigations suggest a role for antioxidants in preventing ID DM. MDL 29,311 (4,4'-[methylenebis (thio)]bis[2,6-bis(1,1-dimethylethy l)]-phenol) is an analogue of the antioxidant probucol. Administered a s a 1% dietary admixture to female nonobese diabetic mice from 4 to 24 wk of age, MDL reduced the prevalence of diabetes from 49 to 4% at 24 wk of age (n = 50-61/group). Discontinuation of treatment at 24 wk of age did not result in a rapid onset of diabetes. Probucol (1%) did no t prevent diabetes. Initiating MDL treatment at 4 or 8 wk of age was m ore effective (19 and 17%, respectively, compared with 60% in control mice) than initiating treatment at 12 wk of age (30% diabetic; n = 28- 35/group). A lower dose of MDL (0.1%), started at 4 wk of age, decreas ed the prevalence of diabetes to 36%. Histopathology indicated that MD L did not prevent insulitis. MDL (0.1%) also was evaluated in combinat ion with immunosuppressants. Compared with control mice (65% diabetic) , the combination of MDL and deflazacort was more effective (21% diabe tic) than either agent alone (39% diabetic for MDL and 59% diabetic fo r deflazacort), whereas the effectiveness of MDL, cyclosporin, and MDL plus cyclosporin was similar (39, 38, and 34% diabetic, respectively) . In another model of IDDM, the multiple-low-dose streptozocin-injecte d mouse, MDL (1%) also reduced the prevalence of diabetes when adminis tered beginning 8 wk before streptozocin (55% diabetic vs. 100% of con trol mice; n = 20-25/group). Probucol (1%) was ineffective. MDL appear s effective in preventing the onset of disease in two mouse models of IDDM.