Effects of long-term oral misoprostol administration on hepatic amino acid-nitrogen metabolism in patients with cirrhosis.
BACKGROUND
The acute infusion of a Prostaglandin of E series 1 (PGE1) analogue results in nitrogen sparing in cirrhosis.


OBJECTIVE
To test the effects of long-term oral PGE1 on hepatic and whole-body nitrogen metabolism.


METHODS
Ten patients with advanced cirrhosis were studied in paired experiments, before and 30-50 days after oral misoprostol therapy. alpha-Amino-nitrogen levels and urea-nitrogen synthesis rate were measured in the post-absorptive state and in response to continuous alanine infusion (2 mmol/kg per hour for 4.5h). Data were used to compute the functional hepatic nitrogen clearance, i.e. the slope of the regression of alpha-amino-N levels to urea-N synthesis rate, and the apparent nitrogen exchange.


RESULTS
Misoprostol reduced urea-N synthesis rate (during fasting and in response to alanine), resulting in a positive nitrogen exchange. The functional hepatic nitrogen clearance slightly increased, and the regression line was rightwards shifted, indicating a reduced urea synthesis rate at any alpha-amino-N concentration. Amino acid- and ammonia-N did not accumulate in plasma. No systematic effects on insulin and glucagon were observed.


CONCLUSIONS
Data are consistent with a nitrogen sparing mechanism of misoprostol, not mediated by hormone levels. These effects may be beneficial in clinical hepatology, and need to be tested in controlled trials.
Bianchi
Giampaolo
G
Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Alma Mater Studiorum, Università di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy. bianmice@almadns.unibo.it
Brizi
Mara
M
Manini
Rita
R
Fabbri
Andrea
A
Loffreda
Stefano
S
Zoli
Marco
M
Marchesini
Giulio
G
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D001806:Blood Urea Nitrogen; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage*; D009584:Nitrogen / Q000378:metabolism; D014508:Urea / Q000378:metabolism
D000596:Amino Acids; D000897:Anti-Ulcer Agents; D007328:Insulin; D016595:Misoprostol; D014508:Urea; D005934:Glucagon; D009584:Nitrogen