Chondroitin sulfate
Encyclopedia
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
(GAG) composed of a chain of alternating sugars (N-acetylgalactosamine
N-Acetylgalactosamine
N-Acetylgalactosamine , is an amino sugar derivative of galactose.-Function:In humans it is the terminal carbohydrate forming the antigen of blood group A....
and glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
). It is usually found attached to proteins as part of a proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Chondroitin sulfate is an important structural component of cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and provides much of its resistance to compression. Along with glucosamine
Glucosamine
Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, cell walls in fungi and...
, chondroitin sulfate has become a widely used dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
for treatment of osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
.
Terminology
Chondroitin sulfate was originally isolated well before the structure was characterised, leading to changes in terminology with time. Early researchers identified different fractions of the substance with letters.| Letter identification | Site of sulfation | Systematic name >- | Chondroitin sulfate A |
carbon 4 of the N-acetylgalactosamine (GalNAc) sugar | >- | carbon 6 of the GalNAc sugar | >- | carbon 2 of the glucuronic acid and 6 of the GalNAc sugar | >- | carbons 4 and 6 of the GalNAc sugar | chondroitin-4,6-sulfate |
"Chondroitin sulfate B" is an old name for dermatan sulfate
Dermatan sulfate
Dermatan sulfate is a glycosaminoglycan found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs....
, and it is no longer classified as a form of chondroitin sulfate.
Chondroitin, without the "sulfate", has been used to describe a fraction with little or no sulfation. However, this distinction is not used by all.
Although the name "chondroitin sulfate" suggests a salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...
with a sulfate counter-anion, this is not the case, as sulfate is covalently attached to the sugar. Rather, since the molecule has multiple negative charges at physiological pH, a cation is present in salts of chondroitin sulfate. Commercial preparations of chondroitin sulfate typically are the sodium salt. Barnhill et al. have suggested that all such preparations of chondroitin sulfate be referred to as "sodium chondroitin" regardless of their sulfation status.
Structure
Chondroitin sulfate chains are unbranched polysaccharidePolysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
s of variable length containing two alternating monosaccharides: D-glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
(GlcA) and N-acetyl-D-galactosamine
N-Acetylgalactosamine
N-Acetylgalactosamine , is an amino sugar derivative of galactose.-Function:In humans it is the terminal carbohydrate forming the antigen of blood group A....
(GalNAc). Some GlcA residues are epimer
Epimer
In chemistry, epimers are diastereomers that differ in configuration of only one stereogenic center. Diastereomers are a class of stereoisomers that are non-superposable, non-mirror images of one another....
ized into L-iduronic acid
Iduronic acid
L-Iduronic acid is the major uronic acid component of the glycosaminoglycans dermatan sulfate, and heparin. It is also present in heparan sulfate although here in a minor amount relative to its carbon-5 epimer glucuronic acid....
(IdoA); the resulting disaccharide
Disaccharide
A disaccharide or biose is the carbohydrate formed when two monosaccharides undergo a condensation reaction which involves the elimination of a small molecule, such as water, from the functional groups only. Like monosaccharides, disaccharides form an aqueous solution when dissolved in water...
is then referred to as dermatan sulfate
Dermatan sulfate
Dermatan sulfate is a glycosaminoglycan found mostly in skin, but also in blood vessels, heart valves, tendons, and lungs....
.
Protein attachment
Chondroitin sulfate chains are linked to hydroxyl groups on serineSerine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residues of certain proteins. Exactly how proteins are selected for attachment of glycosaminoglycans is not understood. Glycosylated serines are often followed by a glycine and have neighboring acidic residues, but this motif does not always predict glycosylation.
Attachment of the GAG chain begins with four monosaccharides in a fixed pattern: Xyl
Xylose
Xylose is a sugar first isolated from wood, and named for it. Xylose is classified as a monosaccharide of the aldopentose type, which means that it contains five carbon atoms and includes an aldehyde functional group. It is the precursor to hemicellulose, one of the main constituents of biomass...
- Gal
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
- Gal - GlcA. Each sugar is attached by a specific enzyme, allowing for multiple levels of control over GAG synthesis. Xylose begins to be attached to proteins in the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, while the rest of the sugars are attached in the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
.
Sulfation
Each monosaccharide may be left unsulfated, sulfated once, or sulfated twice. In the most common scenario, the hydroxyls of the 4 and 6 positions of the N-acetyl-galactosamine are sulfated, with some chains having the 2 position of glucuronic acid. Sulfation is mediated by specific sulfotransferaseSulfotransferase
Sulfotransferases are transferase enzymes that catalyze the transfer of a sulfate group from a donor molecule to an acceptor alcohol or amine. The most common sulfate donor is 3'-phosphoadenosine-5'-phosphosulfate...
s. Sulfation in these different positions confers specific biological activities to chondroitin GAG chains.
Function
Chondroitin's functions depend largely on the properties of the overall proteoglycan of which it is a part. These functions can be broadly divided into structural and regulatory roles. However, this division is not absolute, and some proteoglycans have both structural and regulatory roles (see versicanVersican
Versican, also known as VCAN, is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene....
).
Structural
Chondroitin sulfate is a major component of extracellular matrix, and is important in maintaining the structural integrity of the tissue. This function is typical of the large aggregating proteoglycans: aggrecanAggrecan
Aggrecan also known as cartilage-specific proteoglycan core protein or chondroitin sulfate proteoglycan 1 is a protein that in humans is encoded by the ACAN gene. This gene is a member of the aggrecan/versican proteoglycan family...
, versican
Versican
Versican, also known as VCAN, is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene....
, brevican, and neurocan, collectively termed the lecticans.
As part of aggrecan, chondroitin sulfate is a major component of cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
. The tightly packed and highly charged sulfate groups of chondroitin sulfate generate electrostatic repulsion that provides much of the resistance of cartilage to compression. Loss of chondroitin sulfate from the cartilage is a major cause of osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
.
Regulatory
Chondroitin sulfate readily interacts with proteins in the extracellular matrix due to its negative charges. These interactions are important for regulating a diverse array of cellular activities. The lecticans are a major part of the brain extracellular matrix, where the chondroitin sugar chains function to stabilize normal brain synapses as part of perineuronal nets. The levels of chondroitin sulfate proteoglycans are vastly increased after injury to the central nervous system where they act to prevent regeneration of damaged nerve endings. Although these functions are not as well characterized as those of heparan sulfate
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
, new roles continue to be discovered for the chondroitin sulfate proteoglycans.
In cortical development, chondroitin sulfate is expressed by the Sub Plate and acts as a stop signal for neurons migrating from the Ventricular Zone. Neurons stopping here may then be programmed for further migration to specific layers in the cortical plate.
Medical use
Chondroitin is in dietary supplements used as an alternative medicineAlternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
to treat osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
and also approved and regulated as a symptomatic slow-acting drug for this disease (SYSADOA) in Europe and some other countries. It is commonly sold together with glucosamine
Glucosamine
Glucosamine is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of the polysaccharides chitosan and chitin, which compose the exoskeletons of crustaceans and other arthropods, cell walls in fungi and...
. Chondroitin and glucosamine are also used in veterinary medicine.
Pharmacology
The dosage of oral chondroitin used in human clinical trials is 800–1,200 mg per day. Most chondroitin appears to be made from extracts of cartilaginous cow and pig tissues (cow tracheaVertebrate trachea
In tetrapod anatomy the trachea, or windpipe, is a tube that connects the pharynx or larynx to the lungs, allowing the passage of air. It is lined with pseudostratified ciliated columnar epithelium cells with goblet cells that produce mucus...
and pig ear and nose), but other sources such as shark
Shark cartilage
Shark cartilage is a dietary supplement made from the dried and powdered cartilage of a shark; that is, from the tough material that composes a shark's skeleton. Shark cartilage is claimed to combat and/or prevent a variety of illnesses, most notably cancer. It is often marketed under the names...
, fish, and bird cartilage are also used. Since chondroitin is not a uniform substance, and is naturally present in a wide variety of forms, the precise composition of each supplement will vary. In fact, although many food supplement companies produce their products in compliance with human food processing GMP
Good Manufacturing Practice
"Good manufacturing practice" or "GMP" are practices and the systems required to be adapted in pharmaceutical manufacturing, quality control, quality system covering the manufacture and testing of pharmaceuticals or drugs including active pharmaceutical ingredients, diagnostics, foods,...
, most of them do not produce their products in compliance with the GMP regulations for pharmaceuticals, resulting in products without pharmaceutical requirements.
Recent testing has revealed several flaws in the older testing methods. Without knowing the source of the chondroitin (e.g., shark, porcine, or bovine) and the approximate age of the animal, it is impossible to get a reliable reference standard, and, thus, results from previous testing had yielded percentages between 50 and 400%. In 2007, David Ji et al. reported in the Journal of Analytical Chemistry an extremely accurate method of quantification. The method included using an enzyme to break the chondroitin into its individual unsaturated disaccharides, and then measuring them using HPLC with an ion-pairing column and UV detection.
Clinical studies have not identified any significant side effects or overdoses of chondroitin sulfate, which suggest its long-term safety. The Task Force of the European League Against Rheumatism (EULAR) committee recently granted chondroitin sulfate a level of toxicity of 6 in a 0-100 scale, confirming it is one of the safest drugs for osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
. Moreover, its safety is supported by an absence of drug-drug interactions (chondroitin sulfate is not metabolized by cytochrome P450), and the lack of safe alternatives for patients multi-medicated for osteoarthritis and other accompanying diseases, e.g. diabetes, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
, etc.
While it is a prescription or over-the-counter drug in 22 countries, chondroitin is regulated in the U.S. as a dietary supplement http://nccam.nih.gov/research/results/gait/qa.htm#b2 by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
. As a result, in chondroitin sulfate supplements, there are no mandatory standards for formulation, and no guarantee that the product is correctly labelled. This is not the case in Europe, where there is a chondroitin sulfate formulation approved as a drug and considered as the reference product, with evidenced efficacy and safety demonstrated by clinical trials in osteoarthritic patients. Adebowale et al. reported in 2000 that of 32 chondroitin supplements they analysed, only 5 were labeled correctly, and more than half contained less than 40% of the labeled amount. Hence, the importance of testing the bioequivalence of all chondroitin sulfate formulations with the reference product approved in Europe. However, United States Pharmacopoeia (USP) testing standards now exist for the identification and quantification of chondroitin.
Bioavailability and pharmacokinetics
Pharmacokinetic studies performed on humans and experimental animals after oral administration of chondroitin sulfate revealed that it can be absorbed orally. Chondroitin sulfate shows first-order kinetics up to single doses of 3,000 mg. Multiple doses of 800 mg in patients with osteoarthritis do not alter the kinetics of chondroitin sulfate. The bioavailability of chondroitin sulfate ranges from 15% to 24% of the orally administered dose. More particularly, on the articular tissue, Ronca et al. reported that chondroitin sulfate is not rapidly absorbed in the gastro-intestinal tract and a high content of labeled chondroitin sulfate is found in the synovial fluid and cartilage.Mechanisms of action
The effect of chondroitin sulfate in patients with osteoarthritis is likely the result of a number of reactions including its anti-inflammatory activity, the stimulation of the synthesis of proteoglycans and hyaluronic acid, and the decrease in catabolic activity of chondrocytes inhibiting the synthesis of proteolytic enzymes, nitric oxide, and other substances that contribute to damage cartilage matrix and cause death of articular chondrocytes. A recent review summarizes data from relevant reports describing the biochemical basis of the effect of chondroitin sulfate on osteoarthritis articular tissues. The rationale behind the use of chondroitin sulfate is based on the belief that osteoarthritis is associated with a local deficiency in some natural substances, including chondroitin sulfate.Recently, new mechanisms of action have been described for chondroitin sulfate. In an in vitro study, chondroitin sulfate reduced the IL-1β-induced nuclear factor-kB (NF-κB) translocation in chondrocytes. In addition, chondroitin sulfate has recently shown a positive effect on osteoarthritic structural changes occurred in the subchondral bone.
Clinical trials
Many randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s have been conducted with mixed results. These trials have been summarized:
- Reichenbach et al used explicit methods to conduct and report a systematic reviewSystematic reviewA systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of 20 trials and concluded "large-scale, methodologically sound trials indicate that the symptomatic benefit of chondroitin is minimal or nonexistent. Use of chondroitin in routine clinical practice should therefore be discouraged." - Bruyere et al without using explicit methodology for reviewing trials concluded "there is compelling evidence that glucosamine sulfate and chondroitin sulfate may interfere with progression of OA."
The major trial included in the two review above was the GAIT study. GAIT was funded by National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
to test the effects of chondroitin and glucosamine on osteoarthritis of the knee. This multicenter
Multicenter trial
A multicenter research trial is a clinical trial conducted at more than one medical center or clinic. Most large clinical trials, particularly Phase III trials, are conducted at several clinical research centers...
, placebo-controlled, double-blind
Double-blind
A blind or blinded experiment is a scientific experiment where some of the people involved are prevented from knowing certain information that might lead to conscious or subconscious bias on their part, invalidating the results....
, six month long trial found that glucosamine plus chondroitin had no statistically significant effect on symptoms of osteoarthritis in the overall group of osteoarthritis patients. However, in the moderate-to-severe pain subgroup, the combination of chondroitin and glucosamine was found to be more effective in treating pain than celecoxib
Celecoxib
Celecoxib INN is a sulfa non-steroidal anti-inflammatory drug and selective COX-2 inhibitor used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial...
or chondroitin and glucosamine taken individually. Due to small sample sizes in the sub-group (roughly 250 people), the researchers concluded that this needs further validation. The study also found chondroitin sulfate to have a significant effect in reducing joint swelling, effusion, or both. These results indicate that glucosamine and chondroitin do not effectively relieve osteoarthiritic pain in the overall group of osteoarthritis patients, though it may be an effective treatment for those suffering from moderate-to-severe pain.http://nccam.nih.gov/research/results/gait/qa.htm#c1 Some of the researcher's ties to Pfizer (who makes celecoxib), have brought into question the validity of the study. http://www.huffingtonpost.com/jay-gordon/did-you-understand-the-ar_b_16399.html
Clinical practice guidelines based on trials prior to publication of the negative review by Reichenbach and the negative GAIT trial recommended used of chondroitin. The OARSI (OsteoArthritis Research Society International) recommended chondroitin sulfate as the second-most-effective treatment for moderate cases of osteoarthritis (although the guidelines were published in 2008, the developers closed their search date in January, 2006 prior to the GAIT trial). Likewise, the European League Against Rheumatism (EULAR) supported the usefulness of chondroitin sulfate in the management of knee osteoarthritis and grants the highest level of evidence, 1A, and strength of the recommendation, A, to this product.
Contamination in heparin
On Wednesday, March 19, 2008 the U.S. Food and Drug Administration (FDA) identified "oversulfated chondroitin sulfate" as a contaminant in heparinHeparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
originating from China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
.
In this regard, "it is very important to remark on the relevant chemical differences between the chondroitin sulfate formulation approved in Europe as a drug and considered the reference product, and the “oversulfated chondroitin sulfate” identified as a contaminant in heparin originating from China."
The “oversulfated chondroitin sulfate” is not a product extracted from biological sources; it is synthesized through a sulfation reaction from the biological molecule. This is a semi-synthesis process that uses naturally derived chondroitin sulfate as a reagent in combination with various potentially dangerous chemicals, though their significance in the toxicity of "oversulfated chondroitin sulfate" is not known.
The resulting product contains 3 or 4 sulfate groups per disaccharide, and, therefore, its structure differs considerably from the original one (see #Sulfation section above). Furthermore, analysis of the contaminant unexpectedly revealed an unusual type of sulfation not found in any natural sources of chondroitin sulfate. In addition, a tetrasulfated disaccharide
repeat unit
Repeat unit
An essential concept which defines polymer structure, the repeat unit or repeating unit is a part of a polymer chain whose repetition would produce the complete polymer by linking the repeat units together successively along the chain, like the beads of a necklace.A repeat unit is sometimes called...
has not been isolated to date from animal tissues
Thus, chondroitin sulfate is merely the substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
of the reaction: The final, oversulfated molecule constitutes a new entity, whose pharmacological and clinical properties are most likely very different from the biological molecule, as it is demonstrated in a recent article published in New England Journal of Medicine. In this study, Sasisekharan and colleagues showed that the oversulfated chondroitin sulfate (OSCS) found in contaminated lots of unfractionated heparin
Low molecular weight heparin
In medicine, low-molecular-weight heparin is a class of medication used as an anticoagulant in diseases that feature thrombosis, as well as for prophylaxis in situations that lead to a high risk of thrombosis....
, as well as a synthetically generated OSCS reference standard, directly activated the kinin–kallikrein pathway
Kinin-kallikrein system
The kinin-kallikrein system or simply kinin system is a poorly understood system of blood proteins that plays a role in inflammation, blood pressure control, coagulation and pain...
in human plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
, which can lead to the generation of bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
, a potent vasoactive
Vasoactive
A vasoactive is a pharmaceutical agent that has the effect of either increasing or decreasing blood pressure and/or heart rate. Typically used in a setting where a patient has the blood pressure and heart rate monitored constantly, vasoactive drug therapy is typically "titrated" to achieve a...
mediator. In addition, OSCS induced generation of C3a
C3a (complement)
C3a is a one of the proteins formed by the cleavage of complement component 3; the other is C3b. It stimulates mast cell degranulation, thus triggering an immune response.C3a plays an important role in chemotaxis, though not as important a role as C5a....
and C5a
C5a
C5a is a protein fragment released from complement component C5. In humans, the polypeptide contains 74 amino acids. NMR spectroscopy proved that the molecule is composed of four helices and loops connecting the helices. On the N terminus a short 1.5 turn helix is also present. The longest helix...
, potent anaphylatoxins derived from complement proteins
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
. Chondroitin sulfate A was also tested and it showed no induction of amidol
Amidol
Amidol is a colorless crystalline compound with the molecular structure C6H32OH. It is a dihydrogen chloride salt and is used as a photographic developer. It was introduced as a developing agent for photographic papers in 1892...
lytic
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
activity. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS-induced hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
associated with kallikrein
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...
activation when administered by intravenous infusion in swine. In contrast, none of the three pigs treated with chondroitin sulfate A showed any significant changes in blood pressure or heart rate.
See also
- GoutGoutGout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
- Heparin sulfate - a glycosaminoglycan of major pharmaceutical importance for many decades
- Heparan sulfateHeparan sulfateHeparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
- a glycosaminoglycan component of proteoglycanProteoglycanProteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
s in a wide range of vertebrate & invertebrate life - MethylsulfonylmethaneMethylsulfonylmethaneMethylsulfonylmethane is an organosulfur compound with the formula 2SO2. It is also known by several other names including DMSO2, methyl sulfone, and dimethyl sulfone. This colorless solid features the sulfonyl functional group and is considered relatively inert chemically...
External links
- General Glucosamine and Chondroitin Sulfate information at Arthritis FoundationArthritis FoundationThe Arthritis Foundation is the largest national nonprofit organization solely dedicated to the prevention, control and cure of arthritis, the leading cause of disability in the United States....
- "Product Review: Joint Supplements (Glucosamine, Chondroitin, and MSM)" Summary of a Consumer Labs test of the actual composition of these supplements at consumerlabs.com
- "Glucosamine/Chondroitin Products Not Measuring Up", News report of the analysis of commercial supplements by Adebowale et al. at WebMDWebMDWebMD is an American corporation which provides health information services. It was founded in 1996 by Jim Clark and Pavan Nigam as Healthscape, later Healtheon, and then acquired WebMD in 1999 to form Healtheon/WebMD...
- "Chondroitin Sulfate Manufacturing and Risk of Mad Cow Disease" by Winston Wicomb, Ph.D., September 24, 2002. Information on methods for extraction of chondrotin sulfate from cow trachea, at the Stone Clinic of San Francisco, at stoneclinic.com
- "Testing Status: Chondroitin Sulfate M030009", A thorough review of available information on the use of chondroitin sulfate in humans from the National Toxicology Program at National Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesThe National Institute of Environmental Health Sciences is a part of the National Institutes of Health , which is in turn a part of the Department of Health and Human Services ....
- Chondroitin Sulfate, summary of information on the use of chondroitin sulfate from the publishers of the Physicians' Desk ReferencePhysicians' Desk ReferenceThe Physicians' Desk Reference is a commercially published compilation of manufacturers' prescribing information on prescription drugs, updated annually...
.
- "Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)," ClinicalTrials.gov information on the purpose, design, and analysis of the study at clinicaltrials.gov
- "NIH News: Efficacy of Glucosamine and Chondroitin Sulfate May Depend on Level of Osteoarthritis Pain", Wednesday, February 22, 2006 at National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...