title: An excess of topical calcium and magnesium reverses the therapeutic effect of citrate on the development of corneal ulcers after alkali injury.
abstract: Our purpose was to determine whether chelation of Ca2+ and Mg2+ is the mechanism by which sodium citrate inhibits corneal ulceration in the alkali-injured rabbit eye. The right eyes of 60 albino rabbits (2-2.5 kg) were alkali-injured by filling a 12-mm-diameter plastic well placed on the corneal surface with 0.4 ml of 1 N NaOH. After 35 s the alkali was aspirated, and the well was rinsed with physiological saline. Animals were randomly distributed to three treatment groups of equal size. Two drops of the following topical medications were administered on the hour (14 times per day) for 35 days: physiological saline, 10% citrate in saline, and 346 mM Ca2+, 346 mM Mg2+, and 10% citrate in saline. During the experiment, significantly fewer ulcerations occurred in the citrate-treated eyes (five of 20, 25%) than in the saline-treated eyes (13 of 20, 65%) or in the calcium-magnesium-citrate-treated eyes (15 of 20, 75%). When ulcerations did develop in the citrate group, they occurred significantly later and were less severe than those in the saline and calcium-magnesium-citrate groups. There was a significant increase in the number of eyes with signs of band keratopathy and translucent areas in the calcium-magnesium-citrate group when compared with the other two groups. As in previous studies, sodium citrate significantly inhibited the development of corneal ulcers after alkali injury. The annullment of the favorable effect of citrate on ulceration in the alkali-injured eye by the addition of calcium and magnesium shows that the mechanism of action of citrate is the chelation of these divalent cations.
authors.affiliation: Eye Research Laboratories, Brookwood Medical Center, Birmingham, Alabama 35209, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Haddox
authors.forename: R R
authors.initials: RR
authors.lastname: Pfister
authors.forename: S E
authors.initials: SE
authors.lastname: Slaughter
mesh_terms: D000287:Administration, Topical; D000468:Alkalies / Q000494:pharmacology*; D000818:Animals; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy; D002118:Calcium / Q000494:pharmacology*; D019343:Citric Acid / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D003315:Cornea / Q000187:drug effects; D065306:Corneal Injuries; D003320:Corneal Ulcer / Q000517:prevention & control*; D005126:Eye Burns / Q000139:chemically induced / Q000150:complications; D008274:Magnesium / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D000468:Alkalies; D019343:Citric Acid; D008274:Magnesium; D002118:Calcium