Abstract
Acute and chronic pharmacologic effects of cis-hydroxyproline (cis-Hyp) were studied in mice and rats. Given as a single dose intraperitoneally, cis-Hyp is relatively non-toxic and the LD 50 approaches that of l-proline. Chronic administration of cis-Hyp (200 mg/kg/day) to mice did not affect breaking strength of dermal wounds or content and specific activity of noncollagenous protein in the liver. Although cis-Hyp produced a significant decrease tn noncollagenous protein content of polyvinyl alcohol sponge induced granuloma tissue, collagen content and rate of synthesis in granuloma tissue and liver were increased significantly. Rats given cis-Hyp (200 mg/kg/day subcutaneously in divided doses every 12 hr) and control animals demonstrated identical hepatic microsomal protein, cytochrome P 450 and cytochrome b 5 content. Breaking strength of dermal wounds was increased significantly in treated animals. Ultrastructural analysis of rat liver failed to demonstrate any structural alterations of cellular organelles due to cis-hyp treatment. We conclude that chronic in vivo administration of cis-Hyp does not inhibit collagen synthesis or accumulation in normal or repaired tissues and does not decrease the breaking strength of skin wounds. Other effects on protein metabolism could result from nonspecific, chronic toxicity of cis-Hyp.
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