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Diabetes 54:855-861, 2005
© 2005 by the American Diabetes Association, Inc.

Topical Pretreatment of Diabetic Rats With All-trans Retinoic Acid Improves Healing of Subsequently Induced Abrasion Wounds

Humaira Lateef1, Omorodola I. Abatan2, Muhammad Nadeem Aslam1, Martin J. Stevens2, and James Varani1

1 Department of Pathology, University of Michigan, Ann Arbor, Michigan
2 Department of Internal Medicine, the University of Michigan and the Ann Arbor Veterans Administration Hospital, Ann Arbor, Michigan

In the current study, rats were made diabetic with streptozotocin (STZ) and maintained for 8 weeks, during which time they were treated topically on alternative days with a solution of 0.1% all-trans retinoic acid in a vehicle of 70:30% ethanol/propylene glycol. STZ-induced diabetic rats treated with vehicle served as controls. Additional nondiabetic rats were treated with all-trans retinoic acid or vehicle in parallel. At the end of the 8-week period, rats from all four treatment groups were subjected to abrasion wound formation. Wounds healed more rapidly in vehicle-treated nondiabetic skin than in vehicle-treated diabetic skin (96% of the wound surface area closed in nondiabetic rats within 6 days vs. 41% closed in diabetic rats). Wounds in all-trans retinoic acid-treated diabetic skin healed more rapidly than wounds in vehicle-treated diabetic skin (85% of the wound surface area closed in all-trans retinoic acid-treated diabetic rats vs. 41% closed in vehicle-treated diabetic rats). At the histological level, recently healed skin from vehicle-treated diabetic rats was shown to contain a thin, wispy provisional matrix in which many of the embedded cells were rounded and some were pycnotic. In contrast, a much denser provisional matrix with large numbers of embedded spindle-shaped cells was observed in healed wounds from diabetic skin that had been pretreated with all-trans retinoic acid. The all-trans retinoic acid-treated diabetic skin was histologically similar to vehicle-treated (or all-trans retinoic acid-treated) skin from nondiabetic animals. In light of these findings, we suggest that prophylactic use of retinoid-containing preparations might be useful in preventing the development of nonhealing skin ulcers resultant from minor traumas in at-risk skin.

Address correspondence and reprint requests to James Varani, PhD, Department of Pathology, University of Michigan, 1301 Catherine Road/Box 0602, Ann Arbor, MI 48109. E-mail: varani{at}umich.edu


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Copyright © 2005 by the American Diabetes Association.