The effect of topical use of zeolite clinoptilolite on wound healing in rat ischemic wound model

Oxidative stress secondary to ischemia can cause physiopathological changes that adversely effects wound healing, such as increased tissue MMP, increased extracellular matrix degradation and inadequate reepithelization. We evaluated utility of topical administration of clinoptilolite zeolite which has proven immunstimulating, antitumoral, antimetastatic effects and possible positive effects on wound healing.The subjects were divided into four groups based on ischemia status and the use of clinoptilolite zeolite. A total of 72 -18 in each group- Wistar rats weighing 200-250 g were used. We used bibedicled dorsal flap as an ischemic wound model. Flaps were elevated on the dorsum of the rats. Wounds (1x1 cm) were created at the end of the first day when the ischemia was maximum. Wounds were monitorized and followed up till 14th day. Serum samples were collected at 3, 7 and 14th days for detection of MMP-1 and TIMP-1 levels with biochemical (ELISA) method. Tissue samples were also extracted at the same days underwent histopathologic and immunohistochemical analysis.When the surface areas of the wounds were compared at the end of the 14th day, it was found that the non-ischemic wounds that were treated with clinoptilolite zeolite were the best healing ones. At the end of 3rd day, scores of reepithelization, kollagen deposition and anjiogenesis were higher in non-ischemic group treated with clinoptilolite zeolite but at the end of the 14th day these scores were higher in the group without ischemia and clinoptilolite zeolite. There was no immunohistochemical difference between the groups at the 3rd and the 14th days. Scores of non-ishemic groups were similar to each other but significantly higher than the ischemic groups at the 7th day. While MMP-1 levels were higher in the ischemic group treated with clinoptilolite zeolite at the 7th day, there was no significant difference between groups in TIMP-1 levels and MMP-1/TIMP-1 ratios.Our results showed that topical clinoptilolite zeolite treatment does not provide any positive contribution to ischemic wound healing but accelerates the healing of non-ischemic wounds. It is concluded that clinoptilolite zeolite which is experimentally shown to be effective in non-ischemic wound healing may be used clinically in wounds without circulatory problems.