chondroitin-sulfates and Body-Weight

There is growing evidence of the role that nutrition can play in the management of veterinary patients with osteoarthritis. Current evidence supports nutritional management of body weight and dietary fortification with the long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Additional studies suggest that supplements and diet additives such as glucosamine, chondroitin sulfate, antioxidants, and green-lipped mussel may also have some benefit in managing osteoarthritis. Additional research evaluating pets with naturally occurring disease, using validated owner questionnaires and objective measurements, is needed.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Chondroitin Sulfates; Dietary Supplements; Dog Diseases; Dogs; Fatty Acids, Omega-3; Food, Fortified; Glucosamine; Osteoarthritis

ORG 10172 is a heparinoid with mean molecular weight 6500 daltons. Intravenous bolus injections of ORG 10172 were compared with placebo and heparin injections in 91 separate studies in 83 healthy male subjects. 6400 units ORG 10172 produced a mean maximum change of 14.7 s in kaolin cephalin time (c.f. greater than 120 s for 5000 units heparin). Changes in prothrombin time were minimal (1.6 s for 6400 units ORG 10172 and 4.5 s after 5000 units heparin). A dose-related increase in bleeding time occurred after ORG 10172 and at high doses (greater than 3200 units) some secondary bleeding, which was never serious, occurred at between 1 and 4 h after incision. A dose-dependent reduction in ex vivo platelet adhesiveness was found at 10 min after ORG 10172 injection. ORG 10172 promoted a much smaller release of lipoprotein lipase as compared with heparin. The effect of ORG 10172 on plasma factor Xa activity (one measure of its action) was described by a biexponential decay with a mean distribution half-life of 2.34 (s.e. mean 0.16) h and mean disposition half-life of 17.6 (s.e. mean 1.1) h. It thus has a much longer duration of effect than heparin. There was a linear relationship of plasma anti-Xa response to increasing dose although there was some variability only partly explained by differences in body weight or surface area. ORG 10172 administration by bolus intravenous injection was well tolerated and there was no evidence of adverse effects on clinical chemistry or haematology tests.

Topics: Adolescent; Adult; Bleeding Time; Blood Coagulation Tests; Body Weight; Chondroitin Sulfates; Dermatan Sulfate; Factor X; Factor Xa; Fibrinolytic Agents; Glycosaminoglycans; Half-Life; Heparitin Sulfate; Humans; Kinetics; Lipoprotein Lipase; Male; Partial Thromboplastin Time; Platelet Adhesiveness; Prothrombin Time

Chondroitin sulfate (CS) is a special bioactive substance with lipid metabolism regulation functions; its molecular mechanisms, however, need further study. This study aimed to study the role of gut microbiota and liver metabolome in the anti-obesity effects of CS. The results demonstrated that CS significantly reduced body weight gain and alleviated insulin resistance and dyslipidemia induced by high-fat diet treatment. Moreover, CS interestingly increased the content of Firmicutes in intestinal microbiota. Further studies showed that there were 11 different metabolites involved in metabolic pathways, including the unsaturated fatty acid biosynthesis pathway, primary bile acid biosynthesis, and taurine and hypotaurine metabolism. In addition, Spearman's correlation analysis indicated that the anti-obesity effect of CS is closely related to liver metabolic regulation. Overall, these results provide a possible molecular mechanism by which CS reduces body weight and lipid accumulation.

Topics: Animals; Body Weight; Chondroitin Sulfates; Diet, High-Fat; Gastrointestinal Microbiome; Liver; Metabolome; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis.. Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed.. Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group.. In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Topics: Animals; Ascorbic Acid; Body Weight; Boswellia; Chondroitin Sulfates; Dogs; Fatty Acids, Omega-6; Female; Glucosamine; Male; Osteoarthritis; Plant Extracts; Triterpenes; Vitamin E

The protective effects of a chondroitin sulfate-rich extract (CSE) from skate cartilage against lipopolysaccharide (LPS)-induced hepatic damage were investigated, and its mechanism of action was compared with that of chondroitin sulfate (CS) from shark cartilage. ICR mice were orally administrated 200 mg/kg body weight (BW) of CS or 400 mg/kg BW of CSE for 3 consecutive days, followed by a one-time intraperitoneal injection of LPS (20 mg/kg BW). The experimental groups were vehicle treatment without LPS injection (NC group), vehicle treatment with LPS injection (LPS group), CS pretreatment with LPS injection (CS group), and CSE pretreatment with LPS injection (CSE group). Hepatic antioxidant enzyme expression levels in the CS and CSE groups were increased relative to those in the LPS group. In LPS-insulted hepatic tissue, inflammatory factors were augmented relative to those in the NC group, but were significantly suppressed by pretreatment with CS or CSE. Moreover, CS and CSE alleviated the LPS-induced apoptotic factors and mitogen-activated protein kinase (MAPK). In addition, CS and CSE effectively decreased the serum lipid concentrations and downregulated hepatic sterol regulatory element-binding proteins expression. In conclusion, the skate CSE could protect against LPS-induced hepatic dyslipidemia, oxidative stress, inflammation, and apoptosis, probably through the regulation of MAPK signaling.

Topics: Animals; Body Weight; Cartilage; Chondroitin Sulfates; Lipids; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred ICR; p38 Mitogen-Activated Protein Kinases; Skates, Fish; Tumor Necrosis Factor-alpha

This study investigated the effects of a combination of fucosylated chondroitin sulfate (CHS) and rosiglitazone (RSG) on glucose metabolism in the liver of insulin-resistant C57BL/6J mice fed a high-fat high-sucrose diet for 19 weeks. The results showed that the combination (CHS/RSG) synergistically improved body weight gain, liver weight, fasting blood glucose levels, glucose tolerance on an oral glucose tolerance test, serum insulin levels, homeostasis model assessment indexes, and hepatic glycogen content. In liver tissue, CHS/RSG significantly normalized the activities of hexokinase, pyruvate kinase, and glucose-6-phosphatase. In additionally, it increased the mRNA expression of insulin receptors, insulin receptor substrate 2, phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glycogen synthase, and inhibited glycogen synthase kinase 3β(GSK-3β) mRNA expression in the liver. This suggests that CHS/RSG treatment improves glucose metabolism by modulating metabolic enzymes and strengthening the PI3K/PKB/GSK-3β signal pathway mediated by insulin at the transcriptional level.

Topics: Animals; Blood Glucose; Body Weight; Chondroitin Sulfates; Diet, High-Fat; Drug Synergism; Drug Therapy, Combination; Gene Expression Regulation; Glucose Tolerance Test; Glucose-6-Phosphatase; Glycogen; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hexokinase; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Liver; Male; Mice; Mice, Inbred C57BL; Organ Size; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Pyruvate Kinase; Receptor, Insulin; Rosiglitazone; Sea Cucumbers; Signal Transduction; Thiazolidinediones

The aim of this study was to utilize self-assembled polycaprolactone (PCL)-grafted chondroitin sulfate (CS) as an anticancer drug carrier. We separately introduced double bonds to the hydrophobic PCL and the hydrophilic CS. The modified PCL was reacted with the modified CS through a radical reaction (CSMA-g-PCL). The copolymer without doxorubicin (DOX) was noncytotoxic in CRL-5802 and NCI-H358 cells at a concentration ranging from 5-1000 μg/mL and DOX-loaded CSMA-g-PCL (Micelle DOX) had the lowest inhibitory concentration of 50% cell growth values against the NCI-H358 cells among test samples. The cellular uptake of Micelle DOX into the cells was confirmed by flow cytometric data and confocal laser scanning microscopic images. The in vivo tumor-targeting efficacy of Micelle DOX was realized using an NCI-H358 xenograft nude mouse model. The mice administered with Micelle DOX showed suppressed growth of the NCI-H358 lung tumor compared with those administered with phosphate-buffered saline and free DOX.

Topics: Animals; Body Weight; Cell Line, Tumor; Cell Survival; Chondroitin Sulfates; Doxorubicin; Drug Carriers; Female; Lung Neoplasms; Mice; Mice, Nude; Micelles; Microscopy, Confocal; Nanoparticles; Polyesters; Tissue Distribution; Xenograft Model Antitumor Assays

The purpose of this study was to investigate the anti-arthritic effects of synthesized chondroitin sulfate E hexasaccharide (sCSE-6, CAS 866407-73-0), using a type II collagen-induced arthritis model in mice. sCSE-6 was administered subcutaneously on a daily basis to type II collagen (CII)-sensitized mice from day 0 to day 55. The severity of arthritis, as well as the immunohistological features of the arthritic mice, were analyzed. sCSE-6 inhibited the course of arthritis and restored the body weight loss of CII-immunized mice. An immunohistological analysis showed that bone/cartilage destruction in the arthritic mice was significantly attenuated by sCSE-6 treatment, with a marginal inhibition of synovial inflammation also observed. The beneficial effect of sCSE-6 on bone destruction, which is the most important factor in preventing arthritis, is particularly noteworthy. In summary, sCSE-6 inhibited arthritis and helped to prevent bone and cartilage destruction in a type II collagen-induced arthritis model in mice. The findings indicated that CSE oligosaccharides might be a novel potential therapeutic tool for rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Body Weight; Carbohydrate Sequence; Cartilage; Chondroitin Sulfates; Dexamethasone; Hindlimb; Joints; Male; Mass Spectrometry; Mice; Mice, Inbred DBA; Molecular Sequence Data; Mycobacterium; Spectrometry, Mass, Electrospray Ionization

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 +/- 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 +/- 100.05 ng/ml) was significantly lower than that in the non-HD group (136 +/- 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 +/- 59.71 ng/ml) was lower than that in the non HD group (245.45 +/- 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.

Topics: Animals; Biomarkers; Body Weight; Chondroitin Sulfates; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Hip Dysplasia, Canine; Hyaluronic Acid; Male; Osteoarthritis; Prevalence; Sex Characteristics

Two acute and subchronic oral toxicity studies were conducted in rats to evaluate safety of a patented preparation of hydrolyzed chicken sternal cartilage (BioCell Collagen II) containing collagen type II, chondroitin sulfate, and hyaluronic acid. In the acute oral toxicity study, five males and five females of Sprague-Dawley rats were administered a single dose of 5000 mg of the test product per kg body weight and observed for 14 days. All animals survived and exhibited normal body weight gain throughout the study. Macroscopic necropsy examination conducted on day 15 revealed no gross pathological lesions in any of the animals. In the subchronic study, Sprague-Dawley rats (40 males, 40 females) were divided into four same-sex groups (10 animals/group). Animals in each group were administered daily either 0, 30, 300 or 1000 mg of the test product per kg of body weight for over 90 days. All animals survived and showed no significant changes in their body weights and histopathology. Although some differences were observed between the treated and control animals in several parameters, they were generally not dose-related or considered to be of toxicological significance. In conclusion, the results from the two oral toxicity studies with male and female young adult rats indicated that the test preparation from hydrolyzed chicken sternal cartilage collagen (BioCell Collagen II) was well tolerated at all four doses tested.

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; Body Weight; Cartilage; Chickens; Chondroitin Sulfates; Collagen Type II; Dose-Response Relationship, Drug; Female; Hyaluronic Acid; Hydrolysis; Joint Diseases; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Sternum; Toxicity Tests, Acute; Toxicity Tests, Chronic

The therapeutic effect of glucosamine hydrochloride (GH) and chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1 derivative, on the development of cartilage lesions was investigated in an animal model of osteoarthritis (OA).. The OA model was created by partial medial meniscectomy of the right knee joint (day 0). The rabbits were placed into three experimental groups: operated (OA) rabbits that received placebo treatment, OA rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day 3 and continued for 8 weeks. Macroscopic and histologic analyses were performed on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated by immunohistochemistry.. Only the group receiving combined treatment with GH + CS + fursultiamine showed a significant reduction in the severity of macroscopic and histologic lesions on tibial plateau, which is the weight bearing cartilage surface of the tibia, compared with placebo-treated OA rabbits. This treatment group also revealed a small, but significant, decrease in the body weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in superficial layer stained positive for MMP-1 compared with unoperated control. Rabbits treated with the GH + CS + fursultiamine revealed a significant reduction in the level of MMP-1.. These results suggest that the chondroprotective effect of GH + CS is enhanced by the addition of fursultiamine in experimental OA. This effect was associated with a reduction in the level of MMP-1, which are known to play an important role in the pathophysiology of OA lesions.

Topics: Animals; Body Weight; Cartilage; Chondroitin Sulfates; Disease Models, Animal; Disease Progression; Fursultiamin; Glucosamine; Immunohistochemistry; Male; Matrix Metalloproteinase 1; Osteoarthritis; Protective Agents; Rabbits; Tibia

Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH*), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH* radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH* levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH* production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.

Topics: Animals; Antioxidants; Arthritis; Arthritis, Experimental; Body Weight; Cartilage; Cartilage, Articular; Catalase; Cattle; Chemokine CXCL2; Chemokines, CXC; Chondroitin Sulfates; Collagen; Free Radicals; Glycosaminoglycans; Humans; Hyaluronic Acid; Intercellular Signaling Peptides and Proteins; Joints; Lipid Peroxidation; Male; Monokines; Neutrophils; Pancreatic Elastase; Rats; Rats, Inbred Lew; Vitamin E

To evaluate the antioxidant activity of the glycosaminoglycans hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S), we used a rat model of collagen-induced arthritis (CIA). Arthritis was induced in Lewis rats by multiple intradermal injections of 250 microl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail and into three to five other sites on the back. Rats were challenged again with the same antigen preparation 7 days later. Disease developed about 11 days after the second immunization. The effects of treatment in the rats were monitored by biochemical parameters and by macroscopic and histological evaluations in blood, synovial tissue and articular cartilage. Arthritis produced the following symptoms: severe periarticular erythema, edema and inflammation in the hindpaws; membrane peroxidation in the cartilage of the joints; endogenous antioxidant wasting; high tumour necrosis factor-alpha (TNF-alpha) plasma levels; and synovial neutrophil accumulation. Treatment with HYA and C4S, starting at the onset of arthritis for 10 days, limited the erosive action of the disease in the articular joints of knee and paw, reduced lipid peroxidation, restored the endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase, decreased plasma TNF-alpha levels, and limited synovial neutrophil infiltration. These data confirm that erosive destruction of the joint cartilage in CIA is due at least in part to free radicals released by activated neutrophils and produced by other biochemical pathways. The beneficial effects obtained with the treatment suggest that HYA and C4S could be considered natural endogenous macromolecules to limit erosive damage in CIA or as a useful tool with which to study the involvement of free radicals in rheumatoid arthritis.

Topics: Animals; Arthritis, Experimental; Body Weight; Chondroitin Sulfates; Collagen; Drug Evaluation, Preclinical; Glutathione; Glycosaminoglycans; Hyaluronic Acid; Male; Malondialdehyde; Neutrophils; Peroxidase; Rats; Rats, Inbred Lew; Superoxide Dismutase; Treatment Outcome; Tumor Necrosis Factor-alpha

Glucosamine (G), often combined with chondroitin sulfate (CS), is a popular natural supplement used widely to treat osteoarthritis. However, use of glucosamine has been linked to development of insulin resistance. To assess the association between glucosamine and insulin resistance more closely, we challenged two rat strains highly sensitive to sugar-induced insulin resistance-Sprague-Dawley (SD) and Spontaneously Hypertensive (SHR) rats. Since elevations of systolic blood pressure (SBP) have been found to be an early and highly sensitive sign of insulin resistance in these two rat strains, we used this parameter as our primary endpoint. Four groups of both rat strains received either no agent (control), G, CS, or a combination of both for 9 weeks. The intake of each agent was calculated to be approximately 3-7 times comparable to human dose. Throughout the study, SBP of both strains consuming the two ingredients alone and in combination were not elevated. Rather, they were significantly lower than control, contrary to what is found in glucose-induced insulin resistance in rats. Over the study period, body weights of the four groups of SD and SHR did not vary significantly. Furthermore, no consistent trends in circulating glucose concentrations were found among the four different groups in the two strains after oral challenge with glucose. Finally, no significant histological differences were found in hearts, kidneys, and livers among the various groups of SHR and SD. From the above result, we conclude that glucosamine and chondroitin sulfate given alone or together do not produce insulin resistance or other related perturbations in two rat strains highly sensitive to sugar-induced insulin resistance.

Topics: Administration, Oral; Animals; Blood Glucose; Blood Pressure; Body Weight; Chondroitin Sulfates; Glucosamine; Glucose; Hypertension; Insulin Resistance; Male; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; Time Factors

Topics: Anticoagulants; Body Weight; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Drug Monitoring; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Renal Dialysis; Thrombocytopenia

To study how the concentrations of proteoglycans (PGs) and collagen change in various parts of tibial articular cartilage during aging, and to evaluate the development of spontaneous osteoarthrosis (OA) in guinea pigs.. PGs were extracted from guinea pig cartilage samples using 4M guanidine hydrochloride, and the amount of hydroxyproline was determined in the extraction remainder. The molecular size and aggregation of PGs were analyzed by electrophoresis, and the glycosaminoglycan composition was assessed by high-performance liquid chromatography.. The PG concentration was proportional to the load distribution. However, when OA became histologically manifest, the PG concentration decreased by 50% (from a mean of 44 microg to 22 microg per mg fresh tissue) and the collagen level decreased by 40% (from a mean of 17 microg to 10 microg per mg fresh tissue), while the proportion of water increased by 13% (from a mean of 710 mg to 800 mg per mg fresh tissue).. Unmineralized cartilage can, within physiologic load limits, respond to increased mechanical demands by increasing the PG and collagen concentrations. Beyond a certain limit, however, the cartilage can no longer compensate for further increases in stress, which results in cartilage degeneration and losses of matrix constituents. These losses seemed to appear earlier in the disease process than has been described in previous animal models of secondary OA.

Topics: Aging; Animals; Body Weight; Cartilage, Articular; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Disease Models, Animal; Electrophoresis; Glycosaminoglycans; Guinea Pigs; Hyaluronic Acid; Male; Osteoarthritis; Proteoglycans

Pathophysiological and therapeutic properties of anemia in rats with adjuvant-induced arthritis (AA) were investigated. Both anemia and chronic inflammation were induced in rats by a single injection of Freund's complete adjuvant. This study confirmed other earlier data that these anemic rats with AA had reduced serum iron levels and that the anemia was characterized as mild, non-progressive, hypochromic, microcytic. In addition, our studies showed that these anemic rats had slightly but significantly enhanced erythropoietin titers, but not renal failure; there was no significant difference in blood urea nitrogen and creatinine levels in anemic and normal groups. The anemia in rats with AA was improved by recombinant human erythropoietin (r-HuEPO) at 30 and 100 U/kg/day, given i.v. for 5 days. In contrast, iron-chondroitin-sulfate colloid (10 mg/kg/day, i.v. for 5 days) failed to improve the anemia and to enhance the effects of r-HuEPO. These data suggest that anemia in rats with adjuvant-induced arthritis is distinguished, pathophysiologically and therapeutically, from iron deficiency anemia, hemolytic anemia, and renal anemia.

Topics: Anemia, Hypochromic; Animals; Arthritis, Experimental; Body Weight; Chondroitin Sulfates; Colloids; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Iron; Rats; Rats, Inbred Lew; Recombinant Proteins

Results of several tests in guinea pigs performed in order to check the hypersensitivity hazard of chondroitin sulfate are reported. As per theoretical expectations, no immuno-enhancing effect leading to hypersensitivity was recorded.

Topics: Anaphylaxis; Animals; Body Weight; Chondroitin Sulfates; Dinitrochlorobenzene; Drug Hypersensitivity; Female; Guinea Pigs; Injections, Intradermal; Male; Skin

One and 3 mg/kg iron as Condrofer**, a new soluble formulation of this metal, and 1 mg/kg iron as Proteoferrina*** or ferritin were given orally for 4 weeks to male rats in which severe experimental anaemia had previously been induced (by iron-deficient diet and repeated bleedings). Haematological (erythrocyte count, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, reticulocytes and leukocytes) and blood chemistry (sodium, potassium, iron and total protein) parameters were checked weekly and at the end of the drug administration period. Clinical and behavioral signs, body weight, food intake and necroscopic observations were also recorded. Condrofer time- and dose-dependently improved the general blood picture, the clinical data and the autoptic findings to the point of making these animals significantly approach control rats, save for one parameter, sideremia, which after 4 weeks of treatment remained lower than normal. The most plausible explanation would seem that the severe anaemia interfered both with the physiological iron storage and with the iron-dependent mitochondrial enzymatic systems. Iron (1 mg/kg) daily as Proteoferrina or ferritin was significantly less effective than when this metal was administered as Condrofer, since all the haematological parameters and the clinical, behavioral signs and necroscopic observations were less favourable. The more complete reversal of anaemia in the rats that received Condrofer is, most probably, due to the higher bioavailability of iron administered under this formulation, as demonstrated by iron kinetics after equidoses of iron as Condrofer and Proteoferrina.

Topics: Anemia, Hypochromic; Animals; Body Weight; Chondroitin; Chondroitin Sulfates; Hematocrit; Hemoglobins; Iron; Male; Rats; Rats, Inbred Strains; Reference Values

We studied changes in glycosaminoglycan content and concentration during postresectional compensatory lung growth in adult male rats. After right trilobectomy, left lung dry weight was normal at 4 days, increased 74% between 4 and 7 days, and more slowly over the next week. Total glycosaminoglycan content per milligram dry lung weight increased early and rapidly, reaching 189% of the control value at 4 days postresection. The magnitude and temporal pattern of increase was different for different glycosaminoglycan subtypes. Hyaluronate and chondroitin sulfate content were increased by 198 and 113%, respectively, at 4 days, with no further increases subsequently. Heparan sulfate content increased more slowly and steadily, and dermatan sulfate concentrations did not change. At 4 days, the percent of total glycosaminoglycans that was hyaluronate was almost doubled, whereas the percent that was heparan sulfate was decreased; by day 7 the percent compositions had returned to normal. We conclude that changes in glycosaminoglycans occur early in postresectional lung growth and speculate that they may play a facilitatory role.

Topics: Animals; Body Weight; Chondroitin Sulfates; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Lung; Male; Organ Size; Rats; Rats, Inbred Strains

The initial tissue localization and redistribution of radioactive iron injected intravenously into the rat as ferritin, chondroitin sulfate, and nonviable red cells was determined. Ferritin iron, initially localized in the hepatocyte, showed minimal redistribution over 24 hours in the normal animal. This may be compared with the active release of iron from the reticuloendothelial cell after the intravenous injection of nonviable red cells and chondroitin sulfate iron. All forms of iron were actively mobilized in iron-deficient animals. The effect of chelation of iron by deferoxamine (DFO) on the redistribution pattern over 4 to 6 hours was determined in iron-deficient, normal, iron-loaded, and phenylhydrazine-treated rats to evaluate the effect of iron stores and erythropoiesis. Use of DFO resulted in extensive chelation of radioactive iron within the hepatocyte and greatly reduced the amount of hepatocyte iron available for erythropoiesis. Very little chelation of reticuloendothelial cell-processed iron occurred, and there was little decrease in its utilization for red cell production. Total urinary chelate iron was independent of erythropoiesis but varied in parallel with the iron load of the animal. These studies suggest that DFO does not act on the reticuloendothelial cell but does have at least two sites of action, both of which relate to total storage iron. One involves hepatocyte stores with excretion into the intestinal tract. The other, possibly located at the hepatocyte membrane, results in urinary iron excretion.

Topics: Anemia, Hemolytic; Animals; Body Weight; Chondroitin Sulfates; Deferoxamine; Feces; Ferritins; Half-Life; Hematocrit; Injections, Intravenous; Iron; Iron Radioisotopes; Liver; Male; Mononuclear Phagocyte System; Rats; Rats, Inbred Strains; Tissue Distribution

Evidence in the literature has suggested that alterations in bone glycosaminoglycans (GAGs) are at least partially responsible for the defective calcification in skeletal fluorosis. The major objectives of this study were to quantitate the GAGs of bone from normal and fluorotic rats and to characterize the change in bone GAGs that occurred during maturation. Weanling male rats were fed a semipurified diet and deionized water with or without fluoride (125 ppm) for 1 or 2 months. Also, a control group of rats was pair-fed to the rats receiving fluoride. GAGs were isolated from dry, fat-free tibias and then quantitated by digestion with chondroitinases and chondrosulfatases. Chondroitin-4-sulfate (C4S) comprised 90% of the bone GAGs, while chondroitin-6-sulfate (C6S), dermatan sulfate (DS) and hyaluronic acid (HA) together comprised about 10% of the total bone GAGs. With increasing age, total GAGs, C4S and HA decreased in amount, but DS remained constant. Fluorotic bone (containing in excess of 5000 ppm of fluoride) had three times as much C6S and twice as much DS as bone from weight- and age-matched control rats. Thus, using a controlled experimental animal model, we have demonstrated that specific alterations of bone GAGs result from fluorosis independently of changes in body weight and age.

Topics: Animals; Body Weight; Bone and Bones; Chondroitin Sulfates; Dermatan Sulfate; Fluorides; Glycosaminoglycans; Hyaluronic Acid; Male; Rats; Rats, Inbred Strains; Sodium Fluoride; Tibia

4-Methylumbelliferyl beta-D-xyloside was administered to 9-day-old chick embryos, and the morphological and chemical changes in the embryo were followed daily. Increases in wet weight, Na and Cl content, and visible edema were detectable at 10 days and fully apparent at 11 days. Dry weight increased to the same extent in control and treated embryos for four days, but then diverged. The degree of sulfation of chondroitin sulfate was slightly less in treated than control embryos at 10 days, and reached a steady low value at 11 days. Analysis of glycosaminoglycans in skin, muscle, and aorta showed an increase in chondroitin and its sulfates in the two former tissues but not the latter. In muscle and aorta, the degree of sulfation of chondroitin sulfate was markedly reduced; but in skin the results suggested a more complex picture in which the normal metabolism of glycosaminoglycans was altered. A possible physiological role is suggested for chondroitin sulfate in embryonic soft tissues.

Topics: Abnormalities, Drug-Induced; Animals; Body Weight; Chick Embryo; Chlorides; Chondroitin Sulfates; DNA; Edema; Glycosaminoglycans; Glycosides; Hymecromone; Kinetics; Sodium; Tissue Distribution; Umbelliferones

Wet weights and glycosaminoglycan content were determined for embryo, amnion, and allantois of control chick embryos and embryos injected with 4-methylumbelliferyl beta-D-xyloside at nine days of age. There was an immediate increase in total uronic acid content, but not in uronic acid concentration, in the embryo. No difference could be detected either in fluid volume, nor in content or type of glycosaminoglycan, in the amnion of the two groups. The fluid content of the allantois fo control eggs increased steadily between nine and 14 days, but in treated embryos the fluid content of the allantois remained low for at least a week. Less than 2 mg of uronic acid was present in allantoic fluid of control 16-day-old embryos, while treated embryos had accumulated more than 8 mg. More than 95% of the latter uronic acid was accounted for as chondroitin sulfate linked to methylumbelliferone and with a degree of sulfation of 50-60%. Thus beta-xyloside-treated embryos excrete large amounts of chondroitin sulfate and very little fluid.

Topics: Allantois; Amnion; Animals; Body Fluids; Body Weight; Chick Embryo; Chondroitin Sulfates; Glycosaminoglycans; Glycosides; Hymecromone; Umbelliferones; Uronic Acids

It has been shown that the non-narcotic analgesic salicylamide is teratogenic for rats. When this drug is administered to rats during gestation, sulfate incorporation into the fetal skeleton is reduced. Aims of studies reported here were to examine the effect of salicylamide on the incorporation of radiosulfate into glycosaminoglycans (GAGs) and the biosynthesis of chondroitin 4-sulfate (Ch-4-S) and chondroitin 6-sulfate (Ch-6-S) in fetal rat limbs was studied. Pregnant rats were fed 25% casein diet with or without 2% salicylamide from day 6 to day 17 or day 19 of gestation. The dams were killed on day 17 or day 19 of gestation, 24 hours following an intramuscular injection of sodium 35S-sulfate. Salicylamide administration decreased the levels of radiosulfate in maternal serum and placenta, and impaired the incorporation of radiosulfate into fetal skeletal GAGs. The incorporation of radiosulfate into fetal skeletal GAGs was significantly affected by maternal serum 35S-sulfate, placental 35S-sulfate, litter size, placental weight and fetal weight. After adjusting for these variables, salicylamide administration still had a significant effect, suggesting that salicylamide may have a primary effect in impairing the incorporation of sulfate into fetal skeletal GAGs. Salicylamide administration was found to have no significant effect on the amount of radiosulfate incorporated into Ch-4-S relative to that incorporated into Ch-6-S. The results showed that with increasing gestational age, there was an increase in synthesis of Ch-4-S with a concomitant decrease in synthesis of Ch-6-S. The effect of salicylamide on the calcification of fetal skeletons was studied. Salicylamide administration resulted in a decrease in the calcium content of fetal limb bones, but had no significant effect on maternal serum calcium. The calcium content of fetal limb bones was greatly affected by fetal weight. After adjusting for the fetal weight effect, salicylamide still had a significant effect on the calcium content of fetal limb bones. These results suggest that the degree of sulfation of fetal skeletal GAGs affects the calcification of fetal skeletons.

Topics: Animals; Body Weight; Bone and Bones; Calcification, Physiologic; Calcium; Chondroitin Sulfates; Extremities; Female; Fetus; Gestational Age; Glycosaminoglycans; Pregnancy; Rats; Salicylamides; Sulfates; Sulfur Radioisotopes

Nine-day chick embryos were treated with 4-methylumbelliferyl beta-D-xyloside or beta-aminopropionitrile fumarate, and their gross chemical composition was examined one week later. Total DNA was 10--20% less in embryos treated with either drug than it was in control embryos. Xyloside-treated embryos showed marked increases in percent wet weight and in sodium/DNA and chloride/DNA ratios, and small decreases in protein/DNA, hydroxyproline/DNA and sulfate/DNA. None of these parameters was affected in embryos treated with beta-aminopropionitrile. Approximately 85% of the uronic acid of control embryos was present as chondroitin sulfate, with a degree of sulfation of 80% and charge density of 1.8; all of this chondroitin sulfate was covalently linked to peptide and had a number-average molecular weight of 29,300. In embryos treated with beta-xyloside, 90% of the uronic acid was present as chondroitin sulfate, with a degree of sulfation of 40% and charge density ranging from 1 to 2; 27% of this chondroitin sulfate, with an average molecular weight of 25,400, was peptide linked, while 73% was linked to 4-methylumbelliferone and had an average molecular weight of 22,900. The chemical differences between embryos treated with the xyloside and embryos treated with the lathyrogen reinforce the conclusion on morphological grounds that these are distinct syndromes involving different aspects of the extracellular matrix.

Topics: Abnormalities, Drug-Induced; Aminopropionitrile; Animals; Body Weight; Chick Embryo; Chondroitin Sulfates; DNA; Extracellular Space; Glycosaminoglycans; Glycosides; Hymecromone; Lathyrism; Umbelliferones

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.

Topics: Adrenal Glands; Animals; Body Weight; Brain Chemistry; Brain Stem; Cerebellum; Chondroitin Sulfates; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Male; Organ Size; Rats; Sleep Deprivation; Sleep, REM; Stress, Physiological; Telencephalon