Effects of topical glutathione treatment in rat ischemic wound model

Oxidative stress secondary to ischemia can cause physiopathologic changes that adversely affect wound healing. In this experimental study, we hypothesized that the topical use of esterified glutathione, a well-known antioxidant, can minimize the effects of oxidative stress by an increase in intracellular glutathione and accelerate wound healing by increasing the contraction capacity of fibroblasts and preventing keratinocytes from apoptosis in a rat ischemic wound model. Experimental models were divided into 3 groups as treatment, control, and healthy. Bipedicled flaps were elevated from the dorsum of the rats, and 6-mm punch wounds were created at the end of the first day when the ischemia is most apparent. Wounds were followed histopathologically and immunohistochemically, and matrix metalloproteinase (MMP)-1 and tissue inhibitors of metalloproteinase (TIMP-1) levels were measured by ELISA. Samples were collected at 0, 5, 8, 10, and 12 days. Histopathologic evaluation revealed significant extracellular matrix deposition and reepithelization every fifth day in treatment and healthy groups when compared with control group. Immunohistochemical evaluation revealed increased apoptosis in basal keratinocytes in the control group when compared with the other groups. The evaluation of the samples collected at 5 and 8 days revealed increased MMP-1 levels in treatment and control groups, but the increase in TIMP-1 levels was more significant than MMP-1 levels in treatment group. MMP-1/TIMP-1 ratio was significantly low in the treatment group.Our results showed that topical GSH treatment can reduce oxidative stress, and the reestablishment of the MMP-1/TIMP-1 ratio gives way to adequate and regular extracellular matrix production and reepithelization. It is concluded that esterified GSH, which is experimentally shown to be effective in ischemic wound healing, can be used clinically in ischemic wounds.