chondroitin and Disease-Models--Animal

Topics: Animals; Cartilage, Articular; Chondroitin; Disease Models, Animal; Glycosaminoglycans; Humans; Hydrocortisone; Joint Diseases; Microscopy, Electron; Papain; Rabbits; Sulfates; Synovial Membrane; Synovitis; Vitamin A

Neuropathic pain (NP) is an abnormality resulting from lesion or damage to parts of the somatosensory nervous system. It is linked to defective quality of life and often poorly managed. Due to the limited number of approved drugs, limited efficacy and side effects associated with the approved drugs, drugs or drug combinations with great efficacy and very minimal or no side effects will be of great advantage in managing NP. This study aimed at investigating the synergistic antinociceptive effects of the combination of glucosamine sulphate (GS) (240 mg/kg) and chondroitin sulphate (CS) (900 mg/kg) in chronic constriction injury (CCI)-induced neuropathy in rats. Forty-two Wistar rats were randomly distributed into seven groups (n = 6). Sciatic nerve was ligated with four loose ligatures to induce NP. Effects of drugs were examined on stimulus and non-stimulus evoked potentials, expression of dorsal root ganglia (DRG) pain modulators and structural architecture of DRG. Oral administration of GS and CS for 21 days reduced hyperalgesia, allodynia, sciatic nerve functional aberration and DRG pain modulators. Histopathology and immunohistochemistry revealed restoration of structural integrity of DRG. Our result showed that the combination of GS and CS produced antinociceptive effects by attenuating hyperalgesia, allodynia and downregulation of NP mediators. GS and CS additionally produced synergistic analgesic effect over its individual components.

Topics: Animals; Chondroitin; Chronic Pain; Constriction; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Ganglia, Spinal; Glucosamine; Inflammation; Male; Neuralgia; Rats; Rats, Wistar; Sciatic Nerve

The aim of the present study was to compare the molecular and morphological effects of diacerein and glucosamine-chondroitin drug treatment and intra-articular injection therapy of human deciduous dental pulp stem cells (hDPSCs) in a rat knee model of induced osteoarthritis (OA).. Thirty-six adult male rats were randomly separated into six groups: Control group (without induction of OA), osteoarthritis group 60 (induction of OA, saline gavage started on day 14 and performed for 60 days, followed by euthanasia), osteoarthritis group (induction of OA and euthanasia after 14 days), diacerein group, glucosamine-chondroitin group, and mesenchymal stem cell group. The drug-treated groups were gavaged with 50 mg/kg of diacerein and 400/500 mg/kg of glucosamine-chondroitin starting on dat 14 for 60 days. The cell therapy-treated group received an intra-articular single dose of 8 × 105 hDPSCs on day 14, and euthanasia was performed after 60 days. Lateral femoral condyles were collected and prepared for immunohistochemistry and light microscopy procedures.. The morphological features and immunoexpression of SOX-5, IHH, MMP-8, MMP-13, and Type II collagen were statistically analysed. Our data suggest that hDPSC therapy contributes more actively and effectively in the structural reorganization of lateral femoral condyles. In contrast, the glucosamine-chondroitin sulphate treatment was more effective in inflammatory control, while diacerein showed better results associated with the maintenance of the primordial cartilage.. The positive therapeutic effect of daily administered conventional drugs can be confirmed in a rat model of OA. However, one single dose of locally administered hDPSCs provides significant improvement in tissue regeneration in an OA model.

Topics: Animals; Anthraquinones; Chondroitin; Dental Pulp; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosamine; Humans; Injections, Intra-Articular; Male; Mesenchymal Stem Cells; Osteoarthritis; Rats; Rats, Wistar

Heparan sulfate proteoglycans regulate key steps of blood vessel formation. The present study was undertaken to investigate if there is a functional overlap between heparan sulfate proteoglycans and chondroitin sulfate proteoglycans during sprouting angiogenesis.. Using cultures of genetically engineered mouse embryonic stem cells, we show that angiogenic sprouting occurs also in the absence of heparan sulfate biosynthesis. Cells unable to produce heparan sulfate instead increase their production of chondroitin sulfate that binds key angiogenic growth factors such as vascular endothelial growth factor A, transforming growth factor β, and platelet-derived growth factor B. Lack of heparan sulfate proteoglycan production however leads to increased pericyte numbers and reduced adhesion of pericytes to nascent sprouts, likely due to dysregulation of transforming growth factor β and platelet-derived growth factor B signal transduction.. The present study provides direct evidence for a previously undefined functional overlap between chondroitin sulfate proteoglycans and heparan sulfate proteoglycans during sprouting angiogenesis. Our findings provide information relevant for potential future drug design efforts that involve targeting of proteoglycans in the vasculature.

Topics: Animals; Blotting, Western; Cell Adhesion; Cell Proliferation; Cells, Cultured; Chondroitin; Disease Models, Animal; Endothelium, Vascular; Heparan Sulfate Proteoglycans; Immunohistochemistry; Mice; Neovascularization, Pathologic; Proteoglycans; Signal Transduction; Vascular Endothelial Growth Factor A

In juvenile tree shrews, positioning a negative-power lens in front of an eye produces a hyperopic shift in refractive state and causes a compensatory increase in axial length over several days so that the eye is myopic when the lens is removed. During negative lens compensation, the scleral extracellular matrix is remodeled. A biomechanical property of the sclera, creep rate, increases; during recovery from induced myopia, the creep rate decreases below normal levels. Changes in glycosaminoglycan (GAG) levels, including those of hyaluronan, may participate in these changes in creep rate and, in turn, participate in controlling the axial length and refractive state. This study investigated the unsulfated and sulfated GAG composition of the sclera during compensation for a -5 diopter (D) lens and during recovery.. Capillary electrophoresis was used to assess the relative levels (ng/mg dry scleral weight) of unsulfated GAGs (hyaluronan [HA] and chondroitin [C0S]), sulfated GAGs (chondroitin-4-sulfate [C4S], chondroitin-6-sulfate [C6S], and dermatan sulfate [DS]) in the sclera of groups of tree shrews (n = 5 per group) that wore a monocular -5 D lens for 1, 2, 4, or 11 days or had 11 days of -5 D lens wear followed by 1, 2, or 4 days of recovery from lens wear. The fellow eye served as an untreated control. Groups of normal and plano lens-treated animals provided age-matched values.. Expressed as a fraction of dry weight, levels of HA were lower after 1, 4, and 11 days of -5 D lens wear. Levels of C0S, C6S, and C4S were significantly lower after 4 and 11 days of lens wear. After 1 and 2 days of recovery, GAG levels in the treated eyes were not significantly different from those in control eyes. After 4 recovery days, HA levels were lower, but the levels of all other GAGs were not different in the recovering and control eyes. Some binocular changes also occurred.. The rapid differential decrease in HA levels during negative lens compensation and the absence of any difference after just 1 day of recovery suggest that HA levels may play a previously unrecognized early role in regulating the biomechanical property (creep rate) of the sclera. The reduced levels of the other GAGs, which occur when creep rate is at its peak elevation, and their rapid return to normal after 1 day of recovery suggest that they may also participate in regulating this biomechanical property of the sclera.

Topics: Animals; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Disease Models, Animal; Electrophoresis, Capillary; Female; Hyaluronic Acid; Male; Myopia; Organ Size; Sclera; Sensory Deprivation; Tupaiidae

Heparin exerts beneficial effects in different experimental models of nephropathy, as observed by the preservation of the structural morphology of the kidney after heparin therapy. Here we investigate molecular and cellular events involved in the protective effects of heparin in the progression of renal disease after unilateral ureteral obstruction.. Thirty-six rats were divided into six groups: group C (control) was not subjected to any surgical manipulation; group S (sham) was subjected to surgical manipulation but without ureteral ligation; group UUO was subjected to ureteral obstruction and received no treatment; group UUO + S was subjected to ureteral obstruction and received saline subcutaneously (s.c.) once daily; group UUO + H was subjected to ureteral obstruction and received low molecular weight heparin (LMW-Hep; 4 mg/kg) s.c. once daily; and group C + H was not subjected to any surgical manipulation and received LMW-Hep (4 mg/kg) s.c. once daily. After 14 days, the content of collagen, fibronectin, total glycosaminoglycans (GAGS), chondroitin sulfate/dermatan sulfate proteoglycans (CS/DSPGs), transforming growth factor-beta (TGF-beta) and cellular infiltration were determined in the kidneys by immunohistochemical and biochemical techniques.. Collagen, fibronectin, total GAGS, CS/DSPGs, TGF-beta and cellular infiltration increased significantly in group UUO. LMW-Hep treatment reduced collagen, fibronectin and TGF-beta, but induced an increase in the content of total GAGS, CS/DSPGs and macrophage infiltration in group UUO + H when compared with group UUO.. LMW-Hep diminishes fibrosis in obstructed kidneys by downregulating the synthesis of collagen, fibronectin and TGF-beta. The mechanisms underlying the overproduction of CS/DSPGs and the increase in cellular infiltration upon LMW-Hep administration remain to be elucidated.

Topics: Animals; Biomarkers; Biopsy, Needle; Cell Movement; Chondroitin; Chondroitin Sulfate Proteoglycans; Collagen; Dermatan Sulfate; Disease Models, Animal; Down-Regulation; Fibronectins; Heparin, Low-Molecular-Weight; Immunohistochemistry; Kidney; Macrophages; Male; Probability; Random Allocation; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity; Transforming Growth Factor beta; Up-Regulation; Ureteral Obstruction

The release rates of specific components of the proteoglycan aggregates (G1 domain, the chondroitin sulfate and keratan sulfate containing portion of the protein core, and link protein) of the articular cartilage of mature beagles were studied at early stages of canine experimental osteoarthritis (OA), generated by transection of the anterior cruciate ligament. Analysis of cartilage explants and synovial fluids indicates that at early stages of experimental OA, there is increased release of the proteoglycan aggregates of the articular cartilage. This involves a release from the tissue of the components of the proteoglycan that are specifically involved with aggregation together with the glycosaminoglycans of the proteoglycan. These components were detected at elevated levels in the media of explants of cartilage from the operated joint, and in the synovial fluids of the operated joints.

Topics: Animals; Cartilage, Articular; Chondroitin; Culture Techniques; Disease Models, Animal; Dogs; Extracellular Matrix Proteins; Female; Keratan Sulfate; Osteoarthritis; Proteoglycans; Synovial Fluid

The in vitro and in vivo pharmacological properties of two oversulfated dermatan sulfate (DS) derivatives, S-DS1 and S-DS2, containing 2 and 3.7 sulfate groups/disaccharide unit respectively were compared to those of the parent DS (1 sulfate group/disaccharide unit). In a purified system the ability of S-DS1 and of S-DS2 to catalyse thrombin inhibition by heparin cofactor II was increased by ten- and seventeen-fold respectively. These compounds also had more potent anticoagulant activities in the activated partial thromboplastin time and the thrombin clotting time assays. Plasma immunodepleted in antithrombin III, heparin cofactor II and both cofactors allowed it to be demonstrated that these enhanced anti-coagulant activities were partly (S-DS1) or totally (S-SD2) independent of any plasma cofactors. In spite of these enhanced anticoagulant activities in vitro the oversulfated derivatives did not exhibit an increased antithrombotic activity in a thromboplastin Wessler type model. Moreover, at the doses investigated, S-DS2 had no antithrombotic effect. The influence of oversulfation on the pharmacokinetic pattern of DS was also investigated. As reported for unfractionated heparin, the biological activities generated after IV injection of high doses of S-DS1 and S-DS2 disappeared according to a concave-convex pattern. This may result from the higher affinities of S-DS1 and of S-DS2 toward endothelial cells in comparison with that of DS.

Topics: Animals; Chondroitin; Dermatan Sulfate; Disease Models, Animal; Fibrinolytic Agents; Half-Life; Humans; Metabolic Clearance Rate; Partial Thromboplastin Time; Rabbits; Sulfuric Acids; Thrombosis

Ocular surface drying was studied in rabbits using an experimental model of blinking interruption. This model produces a discontinuity in the pre-corneal tear film after a few minutes of exposure to air. Changes in superficial epithelial cell structure were studied using a scan microscope. A decrease of micro-folds and an increase in epithelial cell desquamation were observed. Prolonged exposure to air produced similar cellular lesions in deeper layers. The instillation of a single mucomimetic eye-drop containing chondroitin sulphate prevented total interruption of epithelial humidification, kept the epithelial surface intact and preserved normal cellular structure.

Topics: Animals; Chondroitin; Chondroitin Sulfates; Cornea; Disease Models, Animal; Epithelium; Microscopy, Electron, Scanning; Ophthalmic Solutions; Rabbits; Xerophthalmia

The radioassay technique with the 113mIndium-iron chondroitin sulfate colloid, developed in our laboratory, revealed that an isolated marrow reticuloendothelial activation takes place after bleeding 15 to 30 ml of blood per kg body weight from a rabbit. It parallels the erythropoietic response very well. The present stimulation method might deserve testing for studies where marrow reticuloendothelial function is important such as in cancer-bearing patients, the effects of anticancer chemotherapy and gross antigenization.

Topics: Acute Disease; Anemia; Animals; Bloodletting; Bone Marrow; Chondroitin; Colloids; Disease Models, Animal; Erythropoiesis; Female; Idoxuridine; Indium; Iron; Liver; Male; Methods; Mononuclear Phagocyte System; Rabbits; Radioisotopes; Spleen

Topics: Animals; Cartilage, Articular; Cetylpyridinium; Chondroitin; Chromatography, Paper; Collagen; Connective Tissue; Contracture; Disease Models, Animal; Glycosaminoglycans; Hexosamines; Hindlimb; Hyaluronic Acid; Immobilization; Joints; Male; Menisci, Tibial; Rabbits; Spectrophotometry, Infrared; Water

Topics: Animals; Arteries; Carbon Isotopes; Chondroitin; Disease Models, Animal; Glycosaminoglycans; Heparin; Hypertension; Lipid Metabolism; Radioactivity; Rats