Radiation hepatology of the rat: Association of the production of prostacyclin with radiation-induced hepatic fibrosis

Journal Article · Mon Jan 01 04:00:00 EST 1996 · Radiation Research

DOI:https://doi.org/10.2307/3579201· OSTI ID:478304

Geraci, J P; Mariano, M S ^[1]

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1. Univ. of Washington, Seattle, WA (United States)

The hypothesis that hepatic fibrosis is preceded by inflammation and formation of prostanoids from arachidonic acid liberated from damaged cell membranes was investigated. Liver slices were prepared using a Krumdieck precision tissue slicer from sham-irradiated rats or from rats whose livers had been irradiated with 25 Gy {sup 137}Cs {gamma} rays in which injury was allowed to develop in vivo for 6 to 55 days. Unused portions of the liver were analyzed for hydroxyproline content to determine hepatic fibrosis. A unique organ culture system was used to incubate liver slices for 2 h. Secretion into the incubation medium of aspartate aminotransferase and 6-keto prostaglandin F{sub 1{alpha}} were measured to quantify damage to the hepatocyte membrane and production of prostacyclin, respectively. A threefold increase in the concentration of 6-keto prostaglandin F{sub 1{alpha}} in the medium was evident by 13 days after irradiation. This elevated concentration of 6-keto prostaglandin F{sub 1{alpha}} persisted for the remainder of the study and preceded fibrosis, as measured by liver hydroxyproline concentration, and hepatocyte membrane damage, as measured by release of aspartate aminotransferase into the incubation medium or plasma. We therefore suggest that, in the nonregenerating liver, damage and breakdown of nonparenchymal liver cell membrane is the principal source of 6-keto prostaglandin F1. These results are also compatible with the supposition that inflammation and release of arachidonic acid metabolites are one of the early biochemical events leading to hepatic fibrosis. How the release of arachidonic acid metabolites might initiate and sustain radiation-induced fibrosis is discussed. An explanation for the difference in liver fibrosis induced by chemicals and radiation is also presented. 30 refs., 5 figs.

• Sponsoring Organization: USDOE
• OSTI ID: 478304
• Journal Information: Radiation Research, Journal Name: Radiation Research Journal Issue: 1 Vol. 145; ISSN 0033-7587; ISSN RAREAE
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ARACHIDONIC ACID
BIOLOGICAL RADIATION EFFECTS
DIGESTIVE SYSTEM DISEASES
FIBROSIS
GAMMA RADIATION
HYDROXYPROLINE
INFLAMMATION
LIVER
LIVER CELLS
METABOLITES
PHOSPHOLIPIDS
RADIATION INJURIES
RATS