Acidified nitrite improves wound healing in type 2 diabetic rats: Role of oxidative stress and inflammation

Purpose: Decreased nitric oxide bioavailability in skin contributes to impaired wound healing in type 2 diabetes (T2D). This study aims at determining effects of acidified nitrite on wound closure as well as inflammatory and antioxidants markers in wound tissue of rats with T2D. Main methods: Skin wound was made on the back of rats 28 days after the induction of T2D (high-fat diet/low-dose of streptozotocin). Control and diabetic rats were subdivided into two subgroups: Untreated control (C), acidified nitrite-treated control (CN), untreated diabetes (D), and acidified nitrite-treated diabetes (DN). Acidified nitrite was applied once daily from day 3 to day 28 and the wounds were photographed for macroscopic changes. On days 3, 7, 14, 21, and 28 after wounding, wound levels of inflammatory and antioxidant markers were measured. Results: Half closure time (CT50%) was significantly lower in acidified nitrite-treated diabetic rats compared to untreated ones (5.1 vs. 8.0 days, P < 0.001). Inflammatory response was delayed in diabetic rats and persistent inflammatory response was observed at day 14 after wounding. Acidified nitrite application restored the inflammatory response and antioxidant levels to control values. Conclusions: Acidified nitrite accelerated wound healing in rats with T2D by restoring delayed inflammatory response and augmentation of antioxidant defense.