Topical application of ‘Hemin’ promotes wound healing in Streptozotocin-induced diabetic rats

Abstract

Hemin may be of potential therapeutic value in wound healing management in diabetics. It is an inducer of heme oxygenase-1, an enzyme which degrades heme and participates in cellular protection against oxidative stress, inflammation and apoptosis. Thus, in the present study, hemin (0.5%) was applied topically over excision wounds, and its therapeutic effect in wound healing evaluated in diabetic rats. Topical hemin application significantly increased the percentage of wound contraction on day 2 in diabetic rats, however, povidone-iodine did the same on day 7 compared to the diabetic control. A significant increase in hydroxyproline and glucosamine content was found on day 14 in the hemin treated wounds of diabetic rats vs. the diabetic control. The histology of the hemin treated rats was in agreement with the cellular proliferation and collagen synthesis in granulation tissue. Hemin significantly increases cytokine IL-10 and decreases TNF-α in the granulation tissue of the healed wounds of diabetic rats. The finding showing the pro-healing effects of hemin was endorsed by inhibition of mRNA expression of pro-inflammatory cytokine TNF-α and adhesion molecule ICAM-1, and up-regulation of anti-inflammatory cytokine IL-10 mRNA. Hence, topical hemin application (i) helps in early and fast wound contraction (ii) enhances the hydroxyproline and glucosamine content of wounds and (iii) modulates pro-healing mRNA expression of cytokines.