# Recent Studies on the Healing Properties of Eicosapentaenoic Acid
## 2 Skin and Its Healing Mechanisms
### Oral Consumption
This was continued until the conclusion of each analysis (biomechanical test and histologic examination). When comparing the wound area of experimental and control groups on day 7 and the quantity of grade three mast cells on days 3 and 5, it was shown to be significantly reduced by omega-3 fatty acids. It was also found that the wound strength significantly increased in the experimental group on day 15 [22]. Notwithstanding the generally acknowledged health advantages of omega-3 fatty acids, particular research has indicated unfavorable outcomes of these substances in the process of wound healing. [PERSON] et al. (2019) examined how oral eicosapentenoic acid (EPA)-rich oil delivery affects mice's ability to repair wounds. Following four weeks of supplementation with 2 g/kg of body weight with EPA-rich oil, mice's serum concentrations of docosahexaenoicenoic acid (DHA; 22:60-3) (33%) and EPA (20:50-3) were higher than those of control mice. The mice who were fed EPA also had skin that contained omega-3 fatty acids. Compared to control mice, mice that received EPA-rich oil showed a delay in the healing process at the 3- and 7-day marks after wounding; however, this delay did not affect the overall time needed for wound closure. Following EPA-rich oil supplementation, collagen reorganization--which affects the integrity of the wound tissue--was compromised. These effects were linked to increased amounts of interleukin-10 (IL-10) in tissue during the early phases of wound healing, as well as twice as many M2 macrophages compared to control rats. Wound closure and collagen organization returned to normal in the absence of IL-10 (IL-10\({}^{-/-}\) mice), indicating that the harmful effects of EPA-rich oil supplementation were caused by the overproduction of IL-10. To sum up, the quality of wound healing was compromised by oral administration of EPA-rich oil, but the wound closure time remained unaffected. This is probably because the anti-inflammatory cytokine IL-10 was elevated [23]. [PERSON] et al. (2019) employed two distinct methods. Two types of mice were used: (1) FAT-1 transgenic mice that were able to produce \(\omega\)-3 FA naturally; and (2) wild-type (WT) mice that were given DHA-enriched fish oil orally. Compared to WT mice, FAT-1 mice exhibited elevated levels of \(\omega\)-3 FA, primarily docosahexaenoicenoic acid (DHA), in both their systemic (serum) and local (skin tissue) samples. Three days following the formation of the wound, the cutaneous wound tissue of FAT-1 mice exhibited decreased IL-10 levels, increased myeloperoxidase (MPO) activity, and higher levels of CXCL-1 and CXCL-2. The presence of inflammatory cells, edema, and an elevated TNF-\(\alpha\) concentration all contributed to the maintenance of inflammation. Isolated from FAT-1 mice, neutrophils and macrophages also produced lower levels of IL-10 and higher levels of TNF-\(\alpha\). On the final day of analysis, which was 14 days after the wound, the mice's wounds were six times larger than those of the WT group due to a delayed wound closure. This was linked to structural features in the restored tissue as well as improper collagen fiber orientation. In a similar vein, the DHA group saw a late inflammatory phase delay. On the third day following skin injury, this group exhibited elevated TNF-\(\alpha\) content and CD45+F4/80+ cells along with reduced concentrations of \(\omega\)-6 FA metabolites and increased concentrations of key metabolites generated from \(\omega\)-3, such as 18-HEPE. In conclusion, both the FAT-1 and DHA groups' increased DHA content retarded the resolution of inflammation and decreased the quality of the skin tissue that healed [24]. [PERSON] et al. [25] showed that EPA supplementation has a negative effect on diabetic mice's ability to heal wounds due to decreased collagen gene expression, poor collagen organization, and a resulting decrease in the resistance of the repaired tissue, mechanistically, via activating PPAR-\(\gamma\) (peroxisome proliferatorator-activated receptors) [19].