Minimal effects of two aldose reductase inhibitors, AL-1576 and AL-4114, after subacute topical-ocular dosing on xenobiotic biotransformation in rabbits

S. G. Sastry, R. A. Sanders, J. C. Veltman, J. B. Watkins

Research output: Contribution to journalArticle

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Abstract

Aldose reductase is believed to be involved in the etiology of diabetic complications, including cataractogenesis, nephropathy, and neuropathy. AL- 1576 and AL-4114, two spirohydantoin aldose reductase inhibitors, were specifically developed for prevention of diabetic cataractogenesis. This study has determined whether AL-1576 and AL-4114 are inducers of biotransformation by assaying the activities of some phase I and phase II enzymes in the liver, kidney, intestine, and five ocular tissues (cornea, lens, iris-ciliary body, retina, and choroid). The aldose reductase inhibitors were administered topically (the intended route for use in preventing cataractogenesis) in two concentrations (0.5 and 5.0%) each 3 times/day to both eyes of New Zealand white rabbits for 14 days. Lenticular aldose reductase activity was decreased by 30-75% by the aldose reductase inhibitors. Monooxygenase activity toward benzo(a)pyrene, ethoxyresorufin, and methoxycoumarin was not increased by AL-1576 or AL-4114 treatment in any tissue. Activities of 1-chloro-2,4-dinitrobenzene glutathione S-transferase, 2-naphthol sulfotransferase, and 1-naphthol UDP-glucuronosyltransferase were not significantly induced in the eight tissues. Clearly, ocular dosing with AL-4114 and AL-1576 for 14 days had little effect on hepatic, intestinal, and ocular biotransformation.

Original languageEnglish (US)
Pages (from-to)1094-1098
Number of pages5
JournalDrug Metabolism and Disposition
Volume23
Issue number10
StatePublished - Jan 1 1995

Fingerprint

Aldehyde Reductase
Xenobiotics
Biotransformation
Rabbits
Tissue
Dinitrochlorobenzene
Ciliary Body
Choroid
Benzo(a)pyrene
Liver
Iris
Diabetes Complications
Mixed Function Oxygenases
Glutathione Transferase
Cornea
Lenses
Intestines
Retina
AL 4114
imirestat

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Minimal effects of two aldose reductase inhibitors, AL-1576 and AL-4114, after subacute topical-ocular dosing on xenobiotic biotransformation in rabbits. / Sastry, S. G.; Sanders, R. A.; Veltman, J. C.; Watkins, J. B.

In: Drug Metabolism and Disposition, Vol. 23, No. 10, 01.01.1995, p. 1094-1098.

Research output: Contribution to journalArticle

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