Official websites use. Share sensitive information only on official, secure websites. Mono-iodo-acetate MIA injections in the rat, appeared to be a convenient model, but the fast and dose-dependent evolution of the OA induced in the animal, required a validation step, to determine the optimal timing to start the PK investigation.
Although measurement of pain remains difficult on animals, assessment of the induced OA, was confirmed through histology examination. There was a strong interest to identify separately HA and CS, so a different radio-labeling was used with tritium for the HA, and carbon 14 for the CS.
Viscosupplementation of synovial fluid with intra-articular IA injections of hyaluronic acid HA is widely used for symptomatic treatment of osteoarthritis OA. Herein we present HCS, a new combination of chemicals, associating HA and chondroitin sulfate CS , both members of the glycosaminoglycan GAGs family, which are major components of the joint.
HA provides viscosity to the synovial fluid and CS provides elasticity to the cartilage. Motion impairment measurements and histological examinations were used to validate the ability of an IA injection of mono-iodoacetate MIA in the knee of rats to induce OA symptoms. Four male Sprague-Dawley rats received a 1 mg MIA injection on day 1, then motor impairment was monitored from day 4 to day Chondrocyte necrosis, loss of GAGs and other cartilage damage were observed.
Plasma and knee cartilage were collected postadministration and the terminal half-life was similar in both matrices about 5 days , for both 3H-HA and 14C-CS. Despite differences in their molecular size, HA and CS showed PK behavior similarly characterized by prolonged residence inside the joint and slow release in plasma, favoring long-term beneficial effects. Curr Ther Res Clin Exp. Osteoarthitis OA is a painful and disabling disease affecting a large number of people older than age 50 years.
