chondroitin-sulfates and Chemical-and-Drug-Induced-Liver-Injury

Move Free Advanced is a widely available dietary supplement in the United States, marketed to comfort sore joints and improve flexibility and mobility. This product contains glucosamine, chondroitin, hyaluronic acid, and Uniflex proprietary extract, which is a combination of Chinese skullcap and black catechu. We describe two patients who developed hepatotoxicity after ingesting a Move Free Advanced product. In both patients, the hepatotoxicity resolved after discontinuation of the supplement. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6 for both patients) between the patients' development of hepatotoxicity and the Move Free Advanced supplement. Based on a review of the literature, the herbal extract Chinese skullcap is the most likely cause of the hepatotoxicity. To our knowledge, these two cases are the first to be published regarding possible hepatotoxicity associated with Move Free Advanced. Patients seeking dietary supplements for osteoarthritis may want to avoid glucosaminechondroitin products such as Move Free Advanced that also contain Chinese skullcap.

Topics: Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Dietary Supplements; Glucosamine; Humans; United States

Although dual endothelin receptor antagonists (ERAs) show great promise for treating various conditions, their propensity to induce liver injury limits their clinical usage. Inflammation and fibrosis are important processes in liver responses to injury and it has been suggested that they and dual ERA-induced liver injury are mediated by the proteoglycan component chondroitin sulfate (CS), which is synthesized by

Topics: Animals; Carbohydrate Sulfotransferases; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Cytokines; Disease Models, Animal; Endothelin Receptor Antagonists; Fibrosis; Glycosaminoglycans; Humans; Liver; Mice; Receptor, Endothelin A; Receptor, Endothelin B; Sulfotransferases

Oligo-peptides, including monomeric amino acids, have received much attention as bioactive molecules and drugs. One of the biggest problems of these compounds, however, is their very short bioavailability due to instant metabolism and rapid excretion. To solve this problem, we newly designed a poly(ethylene glycol) (PEG)-block-polypeptide self-assembling based drug for the treatment of acute liver injury. Here, PEG-block-poly(L-Ornithine) (PEG-b-POrn) was synthesized via a ring opening polymerization, and a nano-sized polyion self-assembling complex (Nano

Topics: Acetaminophen; Ammonia; Animals; Cattle; Cell Survival; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Disease Models, Animal; Drug Delivery Systems; Endothelial Cells; Hyperammonemia; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Nanoparticles; Ornithine; RAW 264.7 Cells

A 5-year-old spayed female Bernese mountain dog, with a chief complaint of vomiting and melena ingested approximately 200 nutritional joint supplement tablets. Despite aggressive therapy, the patient developed a coagulopathy, pancreatitis, peritonitis, acute kidney injury, and was euthanized. Postmortem examination revealed myocardial necrosis, pneumonia, centrilobular hemorrhage and necrosis of the liver, vasculitis, and acute tubular necrosis.

Topics: Animals; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Dog Diseases; Dogs; Drug Overdose; Female; Glucosamine; Multiple Organ Failure

Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis. These molecules are well tolerated with scarce secondary effects. Very few cases of possible hepatotoxicity due to these substances have been described. The aim of this paper is to report the frequency of presumed glucosamine hepatotoxicity in patients with liver disease. A questionnaire was given to 151 consecutive patients with chronic liver disease of different etiology (mean age 59 years, 56.9% women) attended in an outpatient clinic with the aim of evaluating the frequency of consumption of these drugs and determine whether their use coincided with a worsening in liver function test results. Twenty-three patients (15.2%) recognized having taken products containing glucosamine or chondroitin sulfate previously or at the time of the questionnaire. Review of the clinical records and liver function tests identified 2 patients presenting an elevation in aminotransferase values temporarily associated with glucosamine treatment; one of the cases simultaneously presented a skin rash attributed to the drug. Review of these two patients and the cases described in the literature suggest toxicity of glucosamine and chondroitin sulfate. The clinical spectrum is variable, and the mechanism of toxicity is not clear but may involve reactions of hypersensitivity. The consumption of products containing glucosamine and/or chondroitin sulfate is frequent among patients with chronic liver diseases and should be taken into account on the appearance of alterations in liver function tests not explained by the underlying disease.

Topics: Adult; Aged; Aged, 80 and over; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Dietary Supplements; Female; Glucosamine; Hepatitis C, Chronic; Humans; Liver Function Tests; Male; Middle Aged; Risk Factors; Surveys and Questionnaires; Young Adult

Herbal and dietary supplements are widely used as measures to improve and preserve health and well-being. Among the bestselling preparations are dietary supplement containing glucosamine and chondroitine sulfate taken to improve symptoms of osteoarthritis.. We here present a case of a male patient with biopsy-proven acute and severe autoimmune hepatitis subsequent to intake of a preparation containing glucosamine and chondroitine sulfate. Response to steroids was favorable and resulted in complete remission of the patient. Diagnostic work-up of the case revealed no other possible cause of liver injury, and causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) resulted in a possible causal relationship between intake of glucosamine and chondroitine sulfate and the adverse hepatic reaction.. The present case recalls that products containing glucosamine and chondroitine sulfate can occasionally cause acute liver injury mimicking autoimmune hepatitis, and reminds of the potential dangers of compounds with poor efficacy and ill-defined safety records.

Topics: Acute Disease; Aged; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Diagnosis, Differential; Dietary Supplements; Glucosamine; Hepatitis, Autoimmune; Humans; Male

Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl4)-induced acute liver injury. Chondroitin-4-sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation of nuclear factor (NF)-kappaB and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF-kappaB and apoptosis activation in CCl4-induced liver injury in mice.. Acute hepatitis was induced in mice by an i.p. injection of CCl(4). Varying doses of C4S were administered i.p. 1 h before, 6 and 12 h after CCl4 injection. 24 h after CCl4 injection, the mice were killed for biochemical and histological analysis.. CCl4 injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels; and depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF-kappaB translocation and IkBalpha, and increased gene expression of mRNA and protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of caspases-3 and -7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption.C4S treatment inhibited lipid peroxidation; blocked NF-kappaB activation and IkBalpha protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage.. As antioxidants may inhibit NF-kappaB and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF-kappaB and apoptosis activation in hepatic injury.

Topics: Acute Disease; Animals; Antioxidants; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Caspases; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Enzyme Activation; Male; Mice; Mice, Inbred Strains; NF-kappa B; Random Allocation

Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1 ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-alpha, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-alpha levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-alpha, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Catalase; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Glutathione; Glycosaminoglycans; Hyaluronic Acid; Lipid Peroxidation; Liver; Male; Malondialdehyde; Neutrophil Infiltration; Oxidation-Reduction; Peroxidase; Protein Biosynthesis; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

This study was conducted to develop a new biomaterial to be used for an antioxidative drug. In this study, the hepatoprotective effect of chondroitin sulfate (CS) (100 mg/kg and 200 mg/kg body weight) was investigated at the antioxidative enzyme levels of liver total homogenate and mitochondria fraction. And the carbone tetrachloride (CCl(4))-induced rats were used as hepatotoxic models. The CCl(4) induced rat has been widely used as a hepatotoxic model due to its practicality, convenience and cost effectiveness since the generation of free oxygen radicals by CCl(4) injection was proposed as an important causative agent of hepatotoxicity. Malondialdehyde (MDA) levels were determined as well as the activities of superoxide dismutase (SOD), catalase (CAT), reduced-glutathione (GSH), oxidized-glutathione (GSSG) and glutathione peroxidase (GPx) in the liver. In addition, histopathology of liver tissue was investigated. Liver antioxidative enzyme activity was elevated while MDA concentration was decreased in all CS treated animals. The results demonstrated that CS protected oxidative stress in a dose dependent manner. Moreover, inflammation and cirrhosis in liver tissue of CS treated group were significantly decreased. It gave us an impression that CS might be a radical scavenger.

Topics: Animals; Antioxidants; Carbon Tetrachloride Poisoning; Catalase; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Disease Models, Animal; Female; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Lipid Peroxidation; Malondialdehyde; Mitochondria, Liver; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Administration of a single dose of D-galactosamine to rats causes time-dependent, biphasic changes of total glycosaminoglycan synthesis in liver. A rapidly occurring inhibition is followed by a significantly enhanced (greater than 2 fold) production of 35S-labeled glycosaminoglycans in later stages of injury. Degree and duration of the inhibitory phase are dose-dependent; 50% inhibition is reached at 80 mg/kg and maximum inhibition (nearly 80%) at about 300 mg/kg body weight 2 h after injection of D-galactosamine. The hepatotoxin impairs preferentially the production of heparan sulfate, whereas that of chondroitin sulfate and dermatan sulfate is diminished only slightly and for a rather short period of time. The synthesis of the latter, however, is more stimulated than that of heparan sulfate in later stages of injury. The specific radioactivity of 35S-labeled 3'-phosphoadenosine-5'-phosphosulfate (PAPS) did not change significantly during the course of acute liver damage. Glycosaminoglycan synthesis in regenerating liver was nearly unaffected by D-galactosamine. Uridine at the dose applied partially reversed D-galactosamine-inhibited synthesis of proteoheparan sulfate. In accordance with the labeling studies the content of glucosamine-containing glycosaminoglycans in treated liver decreased, whereas that of galactosamine-containing glycosaminoglycans slightly increased, resulting in a nearly 50% reduction of the glucosamine/galactosamine ratio 5 h after administration of D-galactosamine. Ion exchange chromatographic studies of 35S-labeled specific types of glycosaminoglycans from normal and galactosamine-injured liver revealed only minor structural differences.

Topics: Animals; Chemical and Drug Induced Liver Injury; Chondroitin; Chondroitin Sulfates; Dermatan Sulfate; Galactosamine; Glycosaminoglycans; Heparitin Sulfate; Hepatectomy; Liver; Liver Regeneration; Male; Polysaccharides; Rats