Chondroitin

Effects of molecular size and chemical structure on renal and hepatic removal of exogenously administered chondroitin sulfate in rats.

Pecly IM, Melo-Filho NM, Mourao PA.

Laboratorio de Tecido Conjuntivo, Hospital Universitario Clementino Fraga Filho and Instituto de Bioquimica Medica, Centro de Ciencias da Saude, Universidade Federal do Rio de Janeiro, Caixa Postal 68041, Rio de Janeiro, RJ 21941-590, Brazil.

Chondroitin sulfate, a glycosaminoglycan that is widely distributed among mammals, is used as a therapeutic agent in various diseases. Here, we focus on its absorption, excretion and tissue accumulation in rats. The concentration of (35)S-chondroitin sulfate ((35)S-CS) in plasma reaches a peak in the first 5 min after intravenous administration and simultaneously increases in the urine. Approximately 25% of the (35)S found in the urine appears as inorganic sulfate, indicating that (35)S-CS is partially degraded during its renal filtration. The glycosaminoglycan is retained mainly by the liver and the kidney, where the amount of (35)S reaches a plateau in the first 30 min, remains constant up to 2 h and then decreases markedly. Renal filtration and organ accumulation of (35)S-CS decreases as the size of the glycosaminoglycan is reduced, especially in the liver. A derivative of (35)S-CS that resists hyaluronidase digestion due to reduction of its glucuronic acid carboxyl groups appears at lower concentrations in plasma and in urine when compared with native (35)S-CS. This derivative reaches higher levels in the kidney but lower levels in the liver when compared with the native molecule. Overall, our results indicate a balance between renal and hepatic mechanisms for removing chondroitin sulfate from plasma. The renal filtration increases as the molecular weight of the glycosaminoglycan decreases, whereas hepatic removal requires structural integrity and the presence of high-molecular-weight chains.

PMID: 16545912 [PubMed - in process]