Rat lens prostaglandin biosynthesis during galactose-induced cataractogenesis.
The relationship between the development of galactose-induced cataractogenesis and rat lens microsomal prostaglandin (PG) biosynthesis was studied. Within 24 hr of the introduction of 50% galactose to the rat's diet, lens PGF2 alpha production fell dramatically to 31% of control. Following the initial depression of PGF2 alpha biosynthesis, the ability to generate PGF2 alpha in lens microsomes slightly recovered reaching 58- and 53% of controls at day 2 and day 5 on the sugar diet, respectively. Determination of microsomal PGF2 alpha biosynthesis at 9- and 21 days revealed a continued decline in PG synthesis with complete cessation of PGF2 alpha synthesis by day 36 (hypermature cataracts, +5). The decreased PGF2 alpha biosynthetic capacity was a result of decreased cyclo-oxygenase activity since: PGE2 production demonstrated a similar time course for inhibition; and lens microsomes from control and galactose fed rats revealed no difference in the PGs produced from PGH2 endoperoxide. Neither galactose (1 mM) nor galactitol (1 mM), when added to control microsomal preparations inhibited PG biosynthesis, eliminating the possibility of a direct effect of the sugar, or its metabolite, on cyclo-oxygenase activity. While PG biosynthesis was rapidly inhibited by the galactose feeding no changes were observed in basal lens cyclic AMP levels measured during the first 5 days of the feedings. These results demonstrate that depressed PG biosynthesis is an early consequence of galactose feeding.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost; D015232:Dinoprostone; D005690:Galactose; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D015230:Prostaglandin D2; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism; D044262:Prostaglandin H2; D011453:Prostaglandins / Q000096:biosynthesis*; D011457:Prostaglandins D / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000096:biosynthesis; D011463:Prostaglandins H / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D015237:Dinoprost; D000242:Cyclic AMP; D015232:Dinoprostone; D015230:Prostaglandin D2; D005690:Galactose