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

7 Scopus citations

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Minimal effects of two aldose reductase inhibitors, AL-1576 and AL-4114, after subacute topical-ocular dosing on xenobiotic biotransformation in rabbits'. Together they form a unique fingerprint.

  • Cite this