Effects of ebselen on arachidonate metabolism by ocular and non-ocular tissues

Biochemical Pharmacology
J S HurstW M Pierce

Abstract

The formation of cyclooxygenase products in rabbit and rat ocular and non-ocular tissues in vitro, detected by radio-thin-layer chromatography, was inhibited in a concentration-dependent manner by ebselen (PZ 51), an anti-inflammatory seleno-organic compound which has glutathione peroxidase and anti-oxidant activities. The exception was prostaglandin F2 alpha (PGF2 alpha) formation in the rabbit irisciliary body which was stimulated by ebselen in the concentration range 2-10 microM. These observations were confirmed by gas chromatography-mass spectrometry. The concentration that inhibited 50% of prostaglandin biosynthesis (IC50) in the rabbit iris-ciliary body was 9.3 microM. Ebselen also inhibited the formation of 12-hydroxyeicosatetraenoic acid (12-HETE) in rabbit and rat ocular tissues and rabbit platelets. The IC50 in the rabbit cornea was 4 microM, whereas higher concentrations were generally required to achieve similar inhibition in other tissues. The formation of 12-HETE by rabbit spleen, however, was not decreased by ebselen at concentrations that were inhibitory in other tissues.

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Citations

Oct 1, 1995·General Pharmacology·T Schewe
Mar 1, 1993·Free Radical Biology & Medicine·H Sies
Nov 5, 1997·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·J S Hurst, H E Bazan
Aug 11, 1992·Experimental Eye Research·K L KingW M Pierce
Aug 15, 1991·Archives of Biochemistry and Biophysics·F IslamO Hayaishi
Feb 19, 2000·Journal of Neuroscience Research·V Castagné, P G Clarke
Nov 27, 1991·Biochemical and Biophysical Research Communications·J F MaddoxC C Reddy

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