Effects of D-penicillamine on granulation tissue and connective tissue of skin, aorta and bone in rats (Abstract)
Granulation tissue was produced in rats by subcutaneous implantation of viscose-cellulose sponges. After 52 days treatment with D-penicillamine 100 or 500 (mg/kg)/day half of the animals were killed, the rest after an additional 29 days without treatment. Each treatment group had a paired control group. D-penicillamine caused a substantial and dose dependent inhibition of the collagen crosslinking in all tissues as reflected by increased proportions of soluble collagen fractions and aldehyde crosslink precursors in purified collagen. The most marked changes occurred in skin and aorta, in the latter associated with increased tissue weight and water percentage. In purified acid soluble and 60 °C soluble skin collagen the hdroxyproline/proline ratio was increased after D-penicillamine treatment indicating that the degree of proline hydroxylation in these fractions was increased. The amount of granulation tissue was not affected by the treatment, whereas a reduction of the total amount of collagen and DNA in skin was observed. The collagen profile in granulation tissue, skin and bone was not normalized at the end of the experiment, and in aorta excess deposition of collagen and DNA was observed. These findings indicate that D-penicillamine induces qualitative alterations of the granulation tissue of possible significance to its anti-rheumatic efficacy, but that the amount of fibrotic tissue not was influenced. The effect on normal tissues was far more pronounced, and in vascular tissue even progressive.