The Effects of Cyclophosphamide and Azathioprine on Collagen in Skin and Granulation Tissue in Rats, and the Effects of Cyclophosphamide on Collagen in Human Skin

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Abstract
Granulation tissue was produced in rats by subcutaneous implantation of cellulose sponges. The effect of daily intraperitoneal injections of cyclophosphamide or azathioprine on rat skin and granulation tissue was examined after 14 and 42 days. Skin biopsies from patients with glomerulonephritis were analyzed before and after 42 days of treatment with cyclophosphamide or placebo. In the rats, cytostatic treatment caused an increase in the dry weight of the skin, and azathioprine increased the dry weight and the protein content of the granulomas. The increase in the dry weight was accompanied by a decrease in water percentage. The alpha‐amino nitrogen/OH‐proline ratio in purified acid soluble collagen from skin and granulation tissue increased with the dose and duration of cytostatic treatment. No effect on the aldehyde content was observed. Cyclophosphamide caused a decrease in the alpha/beta ratio in acid soluble collagen from granulation tissue, but not in the collagen from the skin. Salt soluble collagen was increased in the skin after 14 days of cytostatic treatment, but remained unchanged in the granulation tissue. In human skin cyclophosphamide caused no statistically significant changes in the amount of salt soluble or total collagen. It is concluded, that daily treatment of rats with cyclophosphamide or azathioprine from 14 to 42 days seems to inhibit the catabolic processes in the skin and granulation tissue, to decrease the hydroxylation of proline in collagen, and to inhibit the intermolecular cross‐linking in collagen.