Selonsertib in skin tissue repair of obese mice

Obesity worsens skin wound healing due to production of oxidants leading to ASK1 activation that is the enzyme responsible for the induction of cell death. The aim of this project was to analyze the effect of ASK1 inhibition in skin tissue repair in obese animals. Male and adult C57BL/6 mice were fed with a diet rich in lipids and sucrose for 8 weeks. After 6 weeks of diet two excisional wounds were created in the dorsum of the animals. The wounds were topically treated with selonsertib, which is a ASK1 inhibitor, and harvested at 8 days after wounding. This project was approved by the Ethics Committee for Animals Use (CEUA n^o 038/2022).  The diet administration increases the body mass and the epididymal fat at 6 or 7 weeks, but the treatment with selonsertib did not change these parameters. Obese animals presented higher serum levels of triglyceride after 7 weeks. Wound closure was lower in obese animals at 8 days after wounding. The treatment with selonsertib did not impact wound closure. Obese animals exhibited an increased width of granular tissue when compared to the control group at 8 days after wounding. In addition, the administration of selonsertib did not alter this parameter. Obese animals showed a reduction in the content of collagen fibers when compared to the control animals at 8 days after wounding. The treatment with ASK1 inhibitor improved the content of collagen fibers in the wound area of obese group at 8 days after wounding. In the measurement of oxidative damage in lipids, obese animals demonstrated higher levels of peroxided lipids in the wound area when compared to control animals at 8 days after wounding. However, selonsertib administration reduced the levels of peroxided lipids in the wound area of obese animals. In conclusion, the treatment with selonsertib did not impact the obesogenic parameters that were tested in the study, but it was effective to increase the content of collagen fibers and to decrease the oxidative damage in lipids.