The effects of topical treatment with acidified nitrite on wound healing in normal and diabetic mice

The effects of the application of a nitric oxide generating acidified nitrite cream comprising sodium nitrite and citric acid, on the healing of incisional wounds in mice, has been investigated. The effects of acidified nitrite on wound healing were critically dependent on the time of application after wounding. Application of acidified nitrite starting on the day of wounding and on consecutive days thereafter significantly inhibited both half time to closure and extent of wound closure. Conversely, application starting on days 1–4 after wounding and on consecutive days thereafter significantly augmented the rate and extent of wound healing. Optimal effects on improving wound healing were observed with cream concentrations of 3.0% (w/v) sodium nitrite and 4.5% (w/v) citric acid. Starting application on day 5 after wounding had no effect on the rate or extent of wound healing. In diabetic Lepr db/db mice, starting treatment at day 2 after wounding, acidified nitrite at 3.0% (w/v) sodium nitrite and 4.5% (w/v) citric acid significantly increased the rate and extent of wound healing. This suggests that acidified nitrite is effective in improving wound healing against a diabetic background. The present data shows that acidified nitrite cream, a clinically effective means of topically delivering nitric oxide, augments the wound healing process and may be of clinical benefit.