Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti-inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing.
In this study the clinical and histopathological effects of topically applied tripeptide-copper complex (TCC) and zinc oxide on open-wound healing in rabbits was evaluated. Eighteen New Zealand rabbits were divided into three groups: TCC, zinc oxide and no treatment. One full thickness wound was created on each side of the dorsal midline in each rabbit. Wound margins were traced on days 0, 7, 14, and 21 and topical TCC and zinc oxide were applied daily for 21 days to each rabbit in the respective treatment groups. The mean unhealed wound area was significantly smaller in the TCC than in the zinc oxide group on day 7, but it was significantly smaller in the TCC group than in to the control group on days 7, 14 and 21. The mean percentage of wound contraction on day 7 was significantly higher in the TCC than in the zinc oxide group; however, it was significantly higher in the TCC group than in the control group on days 7, 14 and 21. Median time for the coverage of the wound bed with granulation tissue was significantly shorter in the TCC group than in the other groups. Filling of the open wound with granulation tissue to skin level was significantly slower in the control group than in the other two groups. Neutrophil counts decreased regardless of the group in parallel with healing, while neovascularization was best observed in the TCC group. The results suggest that TCC is a better choice in the treatment protocols of open wounds in rabbits than zinc oxide.
The aim of this study was to compare the clinical and histopathological effects of tripeptide copper complex (TCC) and two different doses of laser application (helium-neon laser, 1 and 3 J cm(-2)) on wound healing with untreated control wounds. Experimental wounds were created on a total of 24 New Zealand white rabbits and topical TCC or laser was applied for 28 days. The wounds were observed daily, and planimetry was performed on days 7, 14, 21 and 28 to measure the unhealed wound area and percentage of total wound healing. Biopsies were taken weekly to evaluate the inflammatory response and the level of neovascularization. The median time for the first observable granulation tissue was shorter (P < 0.05) in the low and high dose laser groups than in the control group (3 and 2.66 vs. 4.5 days), but was not different between the TCC and control groups (4.16 vs. 4.5 days). Filling of the open wound to skin level with granulation tissue was faster (P < 0.05) in the TCC and high dose laser groups than in the control group (14 and 16 vs. 25 days), but was not different between the low dose laser and control groups (23 vs. 25 days). The average time for healing was shorter (P < 0.05) in the TCC and high dose laser groups (29.8 and 30.2 vs. 34.6 days), but was not different between the low dose laser and control groups (33.8 vs. 34.6 days). Histopathologically, wound healing was characterized by a decrease in the neutrophil counts and an increase in neovascularization. The TCC and high dose laser groups had greater neutrophil and vessel counts than in the control group, suggesting a more beneficial effect for wound healing.
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