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Original Articles

Antioxidant MDL 29,311 Prevents Diabetes in Nonobese Diabetic and Multiple Low-Dose STZ-Injected Mice

  1. Eric W Heineke,
  2. Mary B Johnson,
  3. John E Dillberger and
  4. Keith M Robinson
  1. Marion Merrell Dow Research Institute Cincinnati, Ohio and Indianapolis, Indiana
  1. Address correspondence and reprint requests to Dr. Keith M. Robinson, Marion Merrell Dow Research Institute, 2110 East Galbraith Road, Cincinnati, OH 45215.
Diabetes 1993 Dec; 42(12): 1721-1730. https://doi.org/10.2337/diab.42.12.1721
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Abstract

Recent investigations suggest a role for antioxidants in preventing IDDM. MDL 29,311 (4,4’-[methylenebis(thio)]bis[2,6-bis(1,1-dimethylethyl)]-phenol) is an analogue of the antioxidant probucol. Administered as 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 not prevent diabetes. Initiating MDL treatment at 4 or 8 wk of age was more 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, decreased the prevalence of diabetes to 36%. Histopathology indicated that MDL did not prevent insulitis. MDL (0.1%) also was evaluated in combination with immunosuppressants. Compared with control mice (65% diabetic), the combination of MDL and deflazacort was more effective (21% diabetic) than either agent alone (39% diabetic for MDL and 59% diabetic for 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-injected mouse, MDL (1%) also reduced the prevalence of diabetes when administered beginning 8 wk before streptozocin (55% diabetic vs. 100% of control mice; n = 20–25/group). Probucol (1%) was ineffective. MDL appears effective in preventing the onset of disease in two mouse models of IDDM.

  • Received January 22, 1993.
  • Revision received July 8, 1993.
  • Accepted July 8, 1993.
  • Copyright © 1993 by the American Diabetes Association

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December 1993, 42(12)
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Antioxidant MDL 29,311 Prevents Diabetes in Nonobese Diabetic and Multiple Low-Dose STZ-Injected Mice
Eric W Heineke, Mary B Johnson, John E Dillberger, Keith M Robinson
Diabetes Dec 1993, 42 (12) 1721-1730; DOI: 10.2337/diab.42.12.1721

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Antioxidant MDL 29,311 Prevents Diabetes in Nonobese Diabetic and Multiple Low-Dose STZ-Injected Mice
Eric W Heineke, Mary B Johnson, John E Dillberger, Keith M Robinson
Diabetes Dec 1993, 42 (12) 1721-1730; DOI: 10.2337/diab.42.12.1721
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