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Attenuation of ischemic liver injury by prostaglandin E<inf>1</inf> analogue, misoprostol, and prostaglandin I<inf>2</inf> analogue, OP-41483

Totsuka, E and Todo, S and Zhu, Y and Ishizaki, N and Kawashima, Y and Jin, MB and Urakami, A and Shimamura, T and Starzl, TE (1998) Attenuation of ischemic liver injury by prostaglandin E<inf>1</inf> analogue, misoprostol, and prostaglandin I<inf>2</inf> analogue, OP-41483. Journal of the American College of Surgeons, 187 (3). 276 - 286. ISSN 1072-7515

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Abstract

Background: Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drugrelat ed side effects. This study investigated whether misoprostol, prostaglandin E 1 analogue, and OP-41483, prostaglandin I 2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage. Study Design: Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 μg/kg/min) and for 3 hours after reperfusion (0.5 μg/kg/min). Animals were divided into five groups: untreated control group (n = 10); high-dose misoprostol (total 100 μg/kg) group (MP-H, n = 5); middle-dose misoprostol (50 μg/kg) group (MP-M, n = 5); low-dose misoprostol (25 μg/kg) group (MP-L, n = 5); and OP-41483 group (OP, n = 5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed. Results: Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP- M, MP-L, and OP animals experienced only transient hypotension. Conclusions: These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Totsuka, E
Todo, S
Zhu, Y
Ishizaki, N
Kawashima, Y
Jin, MB
Urakami, A
Shimamura, T
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 3 October 1998
Date Type: Publication
Journal or Publication Title: Journal of the American College of Surgeons
Volume: 187
Number: 3
Page Range: 276 - 286
DOI or Unique Handle: 10.1016/s1072-7515(98)00179-3
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1072-7515
Other ID: uls-drl:31735062127604, Starzl CV No. 2039
Date Deposited: 08 Apr 2010 17:34
Last Modified: 13 Oct 2017 21:55
URI: http://d-scholarship.pitt.edu/id/eprint/5425

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