Marked overproduction of non-cyclooxygenase derived prostanoids (F2-isoprostanes) in the hepatorenal syndrome

J. D. Morrow, K. P. Moore, J. A. Awad, M. D. Ravenscraft, G. Marini, K. F. Badr, R. Williams, L. Jackson Roberts

Research output: Contribution to journalArticlepeer-review

Abstract

In spite of extensive searching for clues to the pathogenesis of the hepatorenal syndrome (HRS), its cause remains an enigma. The renal dysfunction in HRS has been attributed to intense but reversible renal vasoconstriction. This has engendered the hypothesis that the renal vasoconstriction is caused by a circulating factor. Patients with HRS exhibit chronic endotoxemia and may have tissue hypoxia, an environment conducive for the formation of free radicals. Recently, we discovered a series of novel prostaglandin (PG) F2-like compounds, termed F2-isoprostanes, that are produced in vivo as products of free radical catalyzed lipid peroxidation independent of the cyclooxygenase enzyme. One of these compounds, 8-epi-PGF(2α), has been found to be an extremely potent renal vasoconstrictor. Therefore, we quantified levels of these prostanoids in patients with HRS and compared them to various control groups. Plasma levels of these compounds were markedly elevated only in patients with HRS (113 ± 30 pg/ml) (p <0.01) compared to normal controls (19 ± 7 pg/ml), patients with compensated liver disease (20 ± 4 pg/ml), patients with decompensated liver disease (22 ± 4 pg/ml), and patients with chronic renal failure (23 ± 4 pg/ml). The increased levels of these compounds are unlikely the result of reduced hepatic nd renal clearance of the compounds since levels are not markedly increased in patients with either decompensated liver disease or chronic renal failure alone. Whether F2-isoprostanes are the elusive mediators responsible for the renal vasoconstriction in HRS remains to be established. However, these findings do suggest that oxidant injury may be a fundamental abnormality involved in the pathogenesis of HRS.

Original languageEnglish (US)
Pages (from-to)417-420
Number of pages4
JournalJournal of Lipid Mediators
Volume6
Issue number1-3
StatePublished - 1992
Externally publishedYes

Keywords

  • eicosanoid
  • free radical
  • hepatorenal syndrome
  • lipid peroxidation
  • prostanoid
  • vasoconstriction

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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