Table 1.
Effects of systemic NO·-based treatment on wound healing in animals with DM
| Study | Year | Species | DM model | Body weight (g) | Wound | Donor | Dose | Route | Endpoint | Findings |
|---|---|---|---|---|---|---|---|---|---|---|
| Witte et al.86 | 2002 | Male rats | STZ | 225–250 | Incision (7 cm) | L-Arg | 2× 1 g/kg/d | G | Wound healing | ↑ Wound fluid NO· metabolite concentrations ↑ Wound breaking strength ↑ Hydroxyproline concentration ↔ Wound fluid arginase activity ↔ Wound fluid ornithine concentration |
| Shi et al.62 | 2003 | Male rats | STZ | 225–266 | Incision (7 cm) | L-Arg | 1 g/kg/d | IP | Wound healing | ↑ Wound fluid NO· concentration ↑ Wound fluid hydroxyproline ↑ Wound breaking strength ↑ Expression of procollagen I, and III |
| Jerônimo et al.87 | 2016 | Male mice | STZ | 20–25 | Incision (3 cm) | L-Arg | 2 g/kg/d | G | Wound healing | ↑ Collagen synthesis and deposition ↑ Vasculoneogenesis ↑ TGF-β expression ↓ Expression of IL-8 ↓ Polymorphonuclear cell infiltration ↓ Fibrosis |
| Witte et al.86 | 2002 | Male rats | STZ | 225–250 | Incision (7 cm) | SIN-10 | 2× 1 mg/kg/d | G | Wound healing | ↑ Wound breaking strength ↑ Hydroxyproline concentration ↑ MMP-2 ↑ Wound fluid arginase activity |
| Schäffer et al.88 | 2007 | Male rats | BBDP | 220–250 | Incision (7 cm) | SIN-10 | 4 mg/kg/d | G | Wound healing | Restoring NO· metabolite concentrations, wound-breaking strength, and collagen deposition in normoglycemic rats ↑ NO· metabolite concentrations, wound-breaking strength, and collagen deposition in hyperglycemic rats |
| Chen et al.89 | 2019 | Female mice | db/db | NR | Ischemic- excision (6 mm) | DNIC-1 | 0.18 mg/kg every other day | IV | Angiogenesis, wound healing | ↑ Healing rate ↓ Wound closure time ↑ Expression of eNOS, MMP-11, CD31, CD34, and VEGF ↑ Angiogenesis ↓ Inflammation |
Control groups received water or normal saline. BBDP: Biobreeding (i.e., an inbred laboratory rat strain that spontaneously develops autoimmune type 1 diabetes mellitus); CD31: endothelial marker; CD34: endothelial marker; DM: diabetes mellitus; DNIC-1: dinitrosyl iron complexe-1; eNOS: endothelial nitric oxide synthase; G: gavage; GSNO: S-nitrosoglutathione; HIF-1: hypoxia-inducible factor-1; IL: interleukin; IP: intraperitoneal; IV: intravenous; L-Arg: L-arginine; MMP: matrix metalloproteinase; NO·: nitric oxide; NR: not reported; SIN-10: molsidomine; STZ: streptozotocin; TGF-β: transforming growth factor-β; VEGF: vascular endothelial growth factor.