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Comparative study of phase II biotransformation in rabbit ocular tissues
J B Watkins1, D P Wirthwein, R A Sanders
1Medical Sciences Program, Indiana University School of Medicine, Bloomington 47405.
Summary
Rabbit ocular tissues possess significant biotransformation capabilities, particularly the iris/ciliary body and cornea, indicated by phase II enzyme activities. The lens showed minimal activity, suggesting localized metabolic functions within the eye.
Area of Science:
- Ocular pharmacology
- Drug metabolism
- Toxicology
Background:
- Ocular tissues possess metabolic capabilities crucial for drug disposition and toxicity.
- Understanding these capabilities is vital for predicting ocular drug efficacy and safety.
Purpose of the Study:
- To evaluate the biotransformational capacity of rabbit ocular tissues.
- To identify specific ocular tissues involved in phase II drug metabolism.
Main Methods:
- Assayed representative phase II enzymes in five ocular tissues (cornea, iris/ciliary body, choroid, retina, lens).
- Compared enzyme activities to those in liver, kidney, and intestine.
- Measured activities of glutathione S-transferase, N-acetyltransferase, sulfotransferase, and UDP-glucuronosyltransferase.
Main Results:
- Iris/ciliary body showed highest glutathione S-transferase activity.
- Cornea exhibited highest N-acetyl-, sulfo-, and UDP-glucuronosyl-transferase activities.
- Cornea, iris/ciliary body, choroid, and retina demonstrated significant activities for multiple enzymes.
- Lens displayed minimal to no biotransformational activity.
- Ocular enzyme activities were comparable to or exceeded those in kidney and intestine for specific pathways.
Conclusions:
- Rabbit ocular tissues, especially those with good blood supply or external interface, possess significant biotransformation pathways.
- These findings are important for understanding ocular drug metabolism and potential toxicity.
- The cornea and iris/ciliary body are key sites for ocular drug metabolism.