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PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS

Hyaluronic Acid (C H NO )
14 21 11 n
Hyaluronic acid also known as hyaluronan or hyaluronate is an anionic, nonsulfated glycosaminoglycan
made up of alternating N-acetyl-D-glucosamine and D-glucuronic acid monosaccharide units
(Saari et al., 1993). It is distributed widely throughout connective, epithelial, neural tissues and
intracellular fluids including the aqueous and vitreous humour (Martindale, 1996). Hyaluronic acid
is unique among glycosaminoglycans in that it is nonsulfated, and forms in the plasma membrane
instead of the Golgi apparatus (Frasher et al., 1997).

Found naturally in the synovial joints, it owns a key role in musculoskeletal structure as a
cushioning and lubricating agent between joint surfaces against mechanical and chemical damage,
while providing rigidity to vertebrae. Lubrication of the joints and protective action of the cartilage,
as well as anti-inflammatory action are found to be the mechanisms of action of hyaluronic acid
(Tsukasa, 2006). Hyaluronic acid is a high molecular weight glycosaminoglycan (2.4 x 106
Da) in normal joints, where it is responsible for viscoelastic properties of the synovial fluid. In
osteoarthritic joints its concentration and its molecular weight are reduced, which may impair the
viscoelastic protection of articular surfaces. On the other hand, hyaluronic acid is synthesized by
the chondrocytes and plays a major role in the extra-cellular matrix architecture, where it links
aggrecans to form huge macromolecular complexes. Hyaluronic acid binds to numerous cells
through specific transmembrane receptors, the CD-44 receptors and thus plays a role in maintaining
cartilage homeostasis (Chevalier, 2011). CD-44 mediates cell interaction with hyaluronic acid
and the binding of the two, functions as an important part in various physiologic events, such
as cell aggregation, migration, proliferation and activation; cell-cell and cell-substrate adhesion
(Comper, 1996; Chen, 1999). As a visco-supplement, hyaluronic acid is a valued therapeutic
agent in fields as diverse as orthopaedics, dermatology, ophthalmology, ENT (ear, nose, throat),
dentistry and more recently, plastic surgery (Baisse et al., 2003).

TOXICOLOGY Toxicity for hyaluronic acid has not been documented in dogs and cats when administered orally in therapeutic

doses. Hyaluronic acid was not toxic in a wide range of acute animal toxicity studies, over several species and
with different exposure routes (Becker et al., 2009).

DRUG Validated interactions studies do not exist for oral hyaluronic acid preparations. Clinical interactions
INTERACTIONS with other drugs have not been reported.

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