16,16-Dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver.
Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 micrograms per kg (subcutaneous) or 250 micrograms per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetamidobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.
Ruwart
M J
MJ
Diabetes and Gastrointestinal Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.
Rush
B D
BD
Snyder
K F
KF
Peters
K M
KM
Appelman
H D
HD
Henley
K S
KS
D015064:16,16-Dimethylprostaglandin E2 / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D011459:Prostaglandins E, Synthetic; C054703:16,16-dimethylprostaglandin E2 (4-acetamidobenzamido)phenyl ester; D003094:Collagen; D015064:16,16-Dimethylprostaglandin E2; D006909:Hydroxyproline