In vitro inhibition of collagen formation by 2,4-pyridine dicarboxylate and minoxidil in rabbit corneal fibroblasts.

Two anti-fibrotic agents were evaluated in vitro for potential application in trabeculectomy. The rate of collagen formation by cultured rabbit corneal fibroblasts was determined by [H-3]proline uptake and hydroxylation assay. Incubation of fibroblasts, for 96 hours, with 16 mM 2,4-pyridine dicarboxylic acid (2,4-PDCA), a competitive inhibitor of prolyl 4-hydroxylase, decreased [H-3]OH-proline formation from control by 28.2+/-3.9%; (average+/-S.E.M), whereas 10 mM minoxidil, an antihypertensive pyrimidine oxide and a lysyl hydroxylase inhibitor, induced a decrease of 17.3+/-4.5%. Incubating fibroblasts with a mixture of the two inhibitors, 16 mM 2,4-PDCA and 10 mM minoxidil, resulted in a further decrease in [ H]proline incorporation of 40.7+/-5.1%. After 96 hours of incubation with the inhibitors, rabbit corneal fibroblast growth was decreased from control by 17.2+/-4.2% and 10.5+/-4.5% for 16 mM 2,4-PDCA and 10 mM minoxidil, respectively. These effects were dose dependent. The results suggest that both 2,4-PDCA and minoxidil have an inhibitory effect on collagen formation and may be useful in delaying surgical wound healing.