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 [3H]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 [3H]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 [3H]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.
Sharir
M
M
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Research Institute, University of Louisville.
Zimmerman
T J
TJ
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects; D006900:Hydroxylation; D008914:Minoxidil / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits
D004338:Drug Combinations; D011725:Pyridines; C055293:2,4-pyridinedicarboxylic acid; D008914:Minoxidil; D003094:Collagen; D011392:Proline