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.
There has been considerable interest in understanding the effects of antioxidants in flap survival during diabetes. Previous studies showed that chlorogenic acid (CGA) exhibits potent antioxidant effects. We aimed to determine the effects of systemic CGA treatment on skin flap survival in an experimental random-pattern dorsal skin flap model in diabetic rats. Twenty-eight male Wistar rats were divided into four groups: phosphate buffered saline (PBS)-treated or CGA-treated nondiabetic rats, PBS-treated or CGA-treated diabetic rats. Diabetes was induced by streptozotocin (45 mg/kg). Caudally based bipedicled dorsal skin flaps were elevated. CGA (100 mg/kg) or PBS (mL/kg; as vehicle) was administered intraperitoneally once daily. On postoperative day 7, flap survival, regional blood perfusion and microangiography were evaluated. The malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels were evaluated from the flap tissue. Capillary density and vascular endothelial growth factor (VEGF) expression were assessed. Harmful effects of diabetes on flap survival were observed. CGA attenuated these effects and allowed greater survival and blood perfusion. CGA decreased MDA and NO levels and increased GSH and SOD levels. CGA elevated capillary density and VEGF expression. This study showed that peripherally administered CGA significantly improved flap survival in diabetic and nondiabetic rats.Key words antioxidant; chlorogenic acid; diabetes; dorsal skin flap; flap survival; oxidative stress Skin flaps are widely used in the repair of local tissue loss and the reconstruction of several tissue defects. Flap necrosis is frequently observed in flap tissues in the postoperative period and is an unwanted effect of healing. Many factors are known to play a role in this major complication such as ischemia, inadequate blood flow and disturbed venous drainage.
Contents A 2‐year‐old, female Persian cat was presented with a history of distocia. In her first pregnancy, she had whelped four kittens and had eaten all of them right after parturition. She had mated again with the same tomcat. Well‐developed foetuses with weak foetal heart beats were observed in the ultrasonographic examination. En block ovariohysterectomy was performed. Three live and mature foetuses were obtained from the uterus; two of them were female foetuses and had no anatomical problem but the third one exhibiting multiple malformations was a male and diagnosed as ‘schistosoma reflexum’ (SR). The vertebral column deviated markedly to the right (scoliosis) at thoracolumbar region, and the middle lumbar and the sacral vertebrae were directed dorsocranially (lordosis). The entire small intestine, a part of large intestine, stomach, spleen and the right kidney were displayed out of the body, and it seemed that the listed internal organs were protruded from an abdominal cleft associated with the allantoic membrane. Liver, lungs and heart were hypoplastic. The large intestine was seen to have blind end (atresia recti), but anus was normal. Cerebrum and cerebellum were noticed as normal in sizes. Chromosome preparations from lymphocyte cultures of the foetus showed chromosomal aberrations including chromatid and chromosome breaks, exchange figures, non‐homologous pairing, whereas no abnormalities were detected in the chromosome preparations from mother’s cultures. This is probably the first case of SR in a cat, which was examined in detail from clinical, pathological, radiological and chromosomal angles.
We evaluated the presence of estrogen (ER) and progesterone (PR) receptors, and matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) enzymes in 18 feline mammary tubulopapillary carcinomas. Immunohistochemistry was performed to localize ER, PR, MMP-2 and MMP-9 in situ. Western blotting and zymographic analyses also were performed to investigate the presence and activities of MMP-2 and MMP-9 enzymes in fresh tissue homogenates. ER immune expression was detected in five samples (27.7%) and PR was positive in sixteen (88.8%) samples. Diffuse cytoplasmic staining of MMP-2 and MMP-9 in neoplastic mammary epithelial cells, stromal fibroblasts and inflammatory cell was evident. MMP-2 and MMP-9 staining was observed also in metastasizing neoplastic cells within lymphatic vessels. MMP-2 and MMP-9 enzymes and their activities in fresh tumor homogenates were demonstrated by zymography. Comparison of MMP-9 gelatinolytic bands from tumor samples and controls revealed a statistically significant difference. We demonstrated elevated MMP-9 and MMP-2 levels in tumor samples by Western blotting; analysis of protein bands revealed 1.9-to-3 fold increase in MMP-9 in tumor samples and the difference was statistically significant. Our results suggest that the expression of MMP-9 can be an important indicator for tumor progression and the possible metastatic nature of feline tubulopapillary carcinomas.
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