ABSTRACT
The discovery of new pharmacological agents is needed to control the progression of osteoarthritis (OA), characterized by joint cartilage damage. Human OA chondrocyte (OAC) cultures were either applied to S-allylcysteine (SAC), a sulfur-containing amino acid derivative, or colchicine, an ancient anti-inflammatory therapeutic, for 24 h. SAC or colchicine did not change viability at 1 nM-10 µM but inhibited p-JNK/pan-JNK. While SAC seems to be more effective, both agents inhibited reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), lipid hydroperoxides (LPO), advanced lipoxidation end-products (ALEs as 4-hydroxy-2-nonenal, HNE), advanced glycation end-products (AGEs), and increased glutathione peroxidase (GPx) and type-II-collagen (COL2). IL-1ß, IL-6, and osteopontin (OPN) were more strongly inhibited by SAC than by colchicine. In contrast, TNF-α was inhibited only by SAC, and COX2 was only inhibited by colchicine. Casp-1/ICE, GM-CSF, receptor for advanced glycation end-products (RAGE), and toll-like receptors (TLR4) were inhibited by both agents, but bone morphogenetic protein 7 (BMP7) was partially inhibited by SAC and induced by colchicine. Nuclear factor erythroid 2-related factor 2 (Nrf2) was induced by SAC; in contrast, it was inhibited by colchicine. Although they exert opposite effects on TNF-α, COX2, BMP7, and Nrf2, SAC and colchicine exhibit anti-osteoarthritic properties in OAC by modulating redox-sensitive inflammatory signaling.
Subject(s)
Chondrocytes/drug effects , Cysteine/analogs & derivatives , Inflammation/drug therapy , Osteoarthritis/drug therapy , Aged , Antigens, Neoplasm/metabolism , Chondrocytes/metabolism , Cysteine/pharmacology , Female , Humans , Inflammation/metabolism , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , JNK Mitogen-Activated Protein Kinases/metabolism , Male , Middle Aged , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , NF-E2-Related Factor 2/antagonists & inhibitors , NF-E2-Related Factor 2/metabolism , Osteoarthritis/metabolism , Signal Transduction/drug effects , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/metabolismABSTRACT
BACKGROUND: The capsular contracture is one of the main complications after radiotherapy in patients with implant-based reconstruction. The aim of this study is to evaluate the efficacy of ramipril for the prevention of radiation-induced fibrosis around the silicone implant. MATERIALS AND METHODS: Thirty Wistar rats in 5 groups were used. Group 1: implant; group 2: implant + radiation; group 3: ramipril + implant; group 4: ramipril + implant + radiation; group 5: sham. Ramipril treatment was started 5 d before surgery and continued for 12 wk after surgery. A mini silicone implant was placed in the back of the rats. A single fraction of 21.5 Gy radiation was applied. Tissues were examined histologically and immunohistochemically (TGF-ß1, MMP-2, and TIMP-2 expression). The alteration of plasma TGF-ß1 levels was examined before and after the experiment. RESULTS: After applying implant or implant + radiation, capsular thickness, percentage of fibrotic area, tissue and plasma TGF-ß1 levels significantly increased, and MMP-2/TIMP-2 ratio significantly decreased compared with the sham group. In ramipril-treated groups, the decrease in capsular thickness, fibrosis, TGF-ß1 positivity, and an increase in MMP-2/TIMP-2 ratio were found significant. In the ramipril + implant + radiation group, the alteration values of TGF-ß1 dramatically decreased. CONCLUSIONS: Our results show that ramipril reduces radiation-induced fibrosis and contracture. The results of our study may be important for the design of the clinical trials required to investigate the effective and safe doses of ramipril, which is an inexpensive and easily tolerated drug, on humans.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Breast/pathology , Implant Capsular Contracture/prevention & control , Radiation Injuries, Experimental/prevention & control , Ramipril/administration & dosage , Animals , Breast/radiation effects , Breast/surgery , Breast Implantation/adverse effects , Breast Implantation/instrumentation , Breast Implants/adverse effects , Breast Neoplasms/therapy , Female , Fibrosis , Humans , Implant Capsular Contracture/etiology , Implant Capsular Contracture/pathology , Male , Mastectomy/adverse effects , Radiation Injuries, Experimental/etiology , Radiation Injuries, Experimental/pathology , Radiotherapy, Adjuvant/adverse effects , Rats , Silicone Gels/adverse effectsABSTRACT
Electrospinning process has gained importance in the production of wound dressings in recent years. The wound dressings prepared by electrospinning method provide many advantages over conventional wound dressings. The aim of this study was to assess the histological, biochemical, and immunohistochemical evaluation of collagen/doxycycline loaded nanofiber wound dressing in both acute and chronic wound healing. Full-thickness wound model was created on rats and rats were divided in two main groups: normoglycemic (acute) and hyperglycemic (chronic) groups. Each group was divided into three sub groups: not treated (control) group, treated with nanofiber wound dressing group and treated with commercial product group. Wound closure rates were measured. Oxidative events were investigated by biochemical analyses. In addition to histological studies, matrix metalloproteinase, tissue inhibitor of metalloproteinase, vascular endothelial growth factor, basic-fibroblast growth factor, and von Willebrand factor levels were investigated with immunohistochemical studies. According to the biochemical analyses, it was concluded that the nanofiber wound dressing helps to increase antioxidant capacity and decrease lipid peroxidation. Immunohistochemical studies showed that nanofiber wound dressing enhanced angiogenesis and shortened the inflammatory phase. It was concluded that an effective and safe prototype nanofiber wound dressing, which has similar wound healing effect to the commercial product, has been developed to be used in acute or chronic wound treatment.
