Polysulfated Glycosaminoglycan in Animals
Polysulfated glycosaminoglycan (PSGAG) is a semisynthetic glycosaminoglycan prepared from bovine tracheal cartilage and composed of a polymeric chain of repeating disaccharide units. The primary glycosaminoglycan in PSGAG is chondroitin sulfate. PSGAG is approved for intramuscular use in dogs and intra-articular and intramuscular use in horses for the control of clinical signs associated with noninfectious degenerative or traumatic arthritis. In horses, the recommended dosage is 500 mg, IM, every 4 days for 28 days, or 250 mg by intra-articular injection once weekly for 5 weeks. In dogs, the recommended dosage is 2 mg/lb, IM, twice weekly for up to 4 weeks. After intramuscular injection, PSGAG is absorbed into the systemic circulation and eventually incorporated into both healthy and damaged cartilage. The exact mechanism of action is unknown, but in vitro studies show that PSGAG inhibits PGE2 and catabolic enzymes such as stromelysin, elastase, the metalloproteases, and others. PSGAG also increases the synthesis of hyaluronic acid, proteoglycan, and collagen in vitro. Toxicity associated with administration of PSGAG has been minimal. Because PSGAG is chemically similar to heparin, overdosage may inhibit coagulation, and concurrent use of aspirin may prolong bleeding times. The use of PSGAG is contraindicated in septic joints.
Pentosan Polysulfate Sodium in Animals
Pentosan polysulfate sodium (PPS) is a polysulfate ester of xylan, a polymer prepared semisynthetically from beechwood plant material. PPS is chemically and structurally similar to heparin and glycosaminoglycan. The compound is approved by the FDA for use as an oral capsule for the treatment of interstitial cystitis in humans. An injectable product is available for use in humans, dogs, and horses in Australia and other countries. The mechanism of action is unknown. PPS stimulates hyaluronic acid and GAG synthesis in damaged joints, inhibits proteolytic enzymes including metalloproteinases, and scavenges free radicals. PPS may also decrease cytokine activity. In canine models of osteoarthritis, intramuscular administration of PPS significantly decreased overall cartilage damage. Because PPS has a heparin-like structure, coagulopathies may be seen. PPS is administered once a week for 4 consecutive weeks, then once every 6 or 12 months.
Hyaluronan in Animals
Hyaluronan (formerly hyaluronic acid), a polysaccharide of glucuronic acid and glucosamine, is a component of synovial fluid and articular cartilage. In the US, a purified fraction of the sodium salt of hyaluronic acid extracted from rooster combs is available for treatment of horses with osteoarthritis. Hyaluronan is responsible for the viscosity of the synovial fluid and contributes to its lubricating function in joint movement. As with other chondroprotective agents, the mode of action is unclear. However, because synovial fluid viscoelasticity is decreased in osteoarthritis, the intra-articular administration of hyaluronan may improve joint lubrication. Hyaluronan inhibits PGE2 synthesis in vitro and in vivo and may inhibit inflammatory enzymes and reduce pain. Most clinical use has been in horses, in which it appears to have minimal adverse effects.
Orgotein in Animals
Orgotein is a water-soluble metalloprotein containing copper and zinc. Found in low concentrations throughout the body, orgotein has superoxide dismutase activity scavenging free oxygen radicals. Orgotein, available as an injectable formulation, has been used for treatment of soft-tissue inflammation in horses and of arthritis in dogs. Although it has been used as an intramuscular or subcutaneous injection, orgotein is typically administered as an intra-articular injection, because its large molecular size may limit absorption via other routes. Intra-articular administration is effective in cases of acute lameness in horses, although the onset of therapeutic response may be slow (2–6 weeks). Reports indicate that orgotein apparently has a wide safety margin.
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