Mixture of sugar and povidone-iodine stimulates healing of MRSA-infected skin ulcers on db/db mice

Abstract

The topical application of a mixture of sugar and povidone-iodine (PI) has been reported to accelerate the healing of cutaneous wounds and ulcers by promoting reepithelialization and granulation tissue formation, as well as by having an anti-microbial effect. In order to clarify the efficacy of a 70% sugar and 3% PI paste (U-PASTA(SP) on infectious skin ulcers, we made a bacterial infection model using methicillin-resistant Staphylococcus aureus (MRSA) on the skin of diabetic db/db mice, and investigated the effect of the paste on the healing process of wounds. Full-thickness wounds were made on the backs of female diabetic mice, (C57BL/ksJ db/db) and inoculated with S. aureus. SP was applied to the closed wounds for 8 days. The degree of repair was evaluated using three histological parameters: The degree of reepithelialization was given a percentage value of 0-100%; the amount of granulation tissue was quantified by measuring the area of granulation (mm(2)); and the number of capillary lumens in the granulation tissue was counted in the complete wound cross-section at 100x magnification. In addition, the colony-forming units (CFU) of MRSA on the wounds were counted. Continuous MRSA infection in the wounds of db/db mice was demonstrated with macroscopic and histopathological images. Wounding and infection caused by MRSA on the back of the diabetic mice significantly induced delayed reepithelialization, granulation tissue formation with inflammatory cell infiltrate and increased CFU on wounds (P < 0.01, respectively) compared to those of the MRSA-infected normal mice. Application of SP significantly accelerated reepithelialization (P < 0.01) and decreased CFU (P < 0.05) of the ulcers in the MRSA-infected wounds, compared to the non-treated group. Histopathological evaluation and CFU on this animal model revealed no significant difference between Methicilin-sensitive Staphylococcus aureus and MRSA infection. These results indicate that wounding on db/db mice provides a useful animal model of bacterial skin infections, and that SP is an effective topical agent for the treatment of diabetic skin ulcers.