Nitrosoglutathione triggers collagen deposition in cutaneous wound repair

Abstract

The presence of nitric oxide (NO) is associated with enhanced wound fibroblast collagen synthesis; previous observations have focused on the effect of NO on wound collagen content. This article emphasizes the effect of nitrosothiols on wound collagen deposition and matrix-metalloproteinase activity, which is the primary breakdown pathway of collagen. We examined the effects of S-nitrosoglutathione (GSNO) and glutathione (GSH) on rat scar tissue. Hydroxyproline content, matrix metalloproteinase activity, total glutathione, and total nitrite of scar tissue were measured 3, 5, 7, and 10 days after wounding. It was observed that, at Day 5 and Day 10, wound collagen content was 52.0 percent and 47.5 percent higher, respectively, after GSNO administration than in controls (p<0.05). GSH administration decreased wound collagen deposition 76.5 percent by Day 5 (p<0.05). GSH lowered the matrix metalloproteinase activity 67 percent at Day 5 and 50 percent (p<0.05) at Day 10. Nitrite and nitrate levels were 55 percent higher in the GSNO treated rats than in the control group (p<0.05) at Day 3, whereas the GSH-treated groups showed no changes. GSNO increased systemic nitrite 53 percent 3 hours after intraperitoneal injection. Our findings suggest that collagen deposition increases in cutaneous wound healing after the administration of GSNO and that this nitrosothiol does not interfere with the collagenolytic pathway, thus maintaining the physiological conditions necessary for wound healing.