Effects of ebselen on arachidonate metabolism by ocular and non-ocular tissues.
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.
Hurst
J S
JS
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, KY 40202.
Paterson
C A
CA
Bhattacherjee
P
P
Pierce
W M
WM
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001393:Azoles / Q000494:pharmacology*; D015237:Dinoprost / Q000096:biosynthesis; D005123:Eye / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*
D001095:Arachidonic Acids; D001393:Azoles; D006893:Hydroxyeicosatetraenoic Acids; D054833:Isoindoles; D016566:Organoselenium Compounds; D016718:Arachidonic Acid; C042986:ebselen; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015237:Dinoprost; D005978:Glutathione; D012643:Selenium