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Life Flow One
The Solution For Heart Disease

by
Karl Loren

Title: Collagenase inhibitors: rationale for their use in treating corneal ulceration.
Author: Berman
Address
Source: Int Ophthalmol Clin, 1975 Winter, 15:4, 49-66
Abstract: Tissue collagenases have been implicated in corneal ulceration in human corneal disease and in ulceration of the rabbit cornea that has served as a model system. Such enzymes from the rabbit and human cornea are inhibited by metal-binding agents of the EDTA type, by thiols, and by the human serum antiprotease alpha2-macroglobulin. Determination of the relative efficacies of collagenase inhibitors indicates that EDTA and Ca-EDTA are about one hundred times more effective on a molar basis than L-cysteine and its derivatives, N-acetyl-L-cysteine and D-penicillamine. The alpha2-macroglobulin on a molar basis, is superior as an inhibitor to the metal-binding agents and thiols. Although Ca may be a necessary cofactor of the corneal collagenases, such a requirement has not been established unequivocally. Inhibition and isotope studies do indicate a requirement for Zn. Thiols are thought to inhibit corneal collagenases by binding to or removing an intrinsic metal cofactor (Zn), and/or possibly by reducing one or more disulfide bonds. Inhibition by both EDTA-type agents and thiols is largely reversible by dialysis. The human alpha2-macroglobulin appears to inhibit corneal colleagenases irreversibly by forming tight complexes with them. Ca-EDTA, cysteine, and acetylcysteine, given as eyedrops, are able to prevent or retard ulceration in the alkali-burned rabbit cornea. They appear to have some efficacy in the prevention of corneal ulceration in humans. EDTA-type compounds are quite stable under routine storage, while acetylcysteine is more stable than cysteine. EDTA is quite toxic and should not be used as eye medication. Ca-EDTA has a low toxicity, and cysteine and acetylcysteine have even lower toxicity. It is not yet certain which inhibitor has the most favorable therapeutic index for clinical use, or is the optimal mode of drug delivery known. However, the collagenase inhibitors seem to have therapeutic promise in the prevention of corneal ulceration.
Language of Publication: English
Unique Identifier: 76189571

MeSH Heading (Major): Corneal Ulcer|*DT; Microbial Collagenase|*AI/ME
MeSH Heading: alpha 1-Antitrypsin|TU; alpha-Macroglobulins|TU; Acetylcysteine|AE/TU; Animal; Calcium|AE/ME/TU; Cyclic AMP|PH; Cysteine|AE/ME/TU; Disease Models, Animal; Edetic Acid|AE/ME/TU; Human; Peptide Hydrolases|AI; Steroids|PH; Tropocollagen; Zinc Radioisotopes

Publication Type: JOURNAL ARTICLE; REVIEW
ISSN: 0020-8167
Country of Publication: UNITED STATES

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