Effect of Low Dosage Schedule of D-Penicillamine on Collagen Cross-Linking in a Nine Week Immobilized Rabbit Knee

Rabbits immobilized with one leg pinned in a fully flexed position, were treated with 60 mg of D-penicillamine/kg three times a week for 9 weeks. After this period of immobilization the animals were sacrificed and the periarticular connective tissue collagen reduced with [3H] NaBH4 for determination of collagen cross-links. There was a significant decrease in the formation of cross-links in the control and immobilized knee in the treated animals as compared to the untreated animals. Penicillamine also blocked the increase in DHLNL, HLNL and HHMD previously demonstrated in immobilized rabbit knees. This is the first demonstration that in vivo administration of penicillamine directly inhibits cross-linking reactions in collagen.