Sorbinil prevents the galactose-induced inhibition of prostaglandin synthesis in lens cells.
The relationship between microsomal prostaglandin biosynthesis, PGH synthase activity and cell morphology was investigated with cultured bovine lens epithelial cells under physiological and hypergalactosemic conditions. The rate of lens cell microsomal PGE2 generation fell from 5.3 to 2.2 pg micrograms protein-1 min-1; PGF2 alpha declined from 7.7 to 4.8 pg micrograms protein-1 min-1 within 20 hr of exposure to 40 mM galactose. The decreased PGE2 and PGF2 alpha biosynthetic capability was attributed to a reduction in PGH synthase activity which reduced to 62% of control (5.5 mM glucose) after a 20 hr exposure to galactose. Measurement of PGH synthase activity after 6 days of continuous exposure to galactose resulted in a further reduction to 55% of control. The diminution in microsomal prostagladin biosynthesis and decline in PGH synthase activity precluded ultrastructural alterations, such as large vacuole formation and severe autodegradation of organelles. The simultaneous introduction of sorbinil, an aldose reductase inhibitor, to the galactose medium not only prevented the decrease in microsomal prostaglandin biosynthesis and PGH synthase activity, but also the detrimental morphological complications. The lens epithelial cell system may provide a useful model for examining the biochemical and morphological-related consequences of sustained hypergalactosemia and their potential regulation by aldose reductase inhibitors.
D000818:Animals; D002417:Cattle; D002455:Cell Division; D005690:Galactose / Q000037:antagonists & inhibitors* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008854:Microscopy, Electron; D008861:Microsomes / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay
D007093:Imidazoles; D048289:Imidazolidines; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; C026411:sorbinil; D005690:Galactose