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Protection by 16,16‐dimethyl prostaglandin E 2 and dibutyryl cyclic AMP against complement‐mediated hepatic necrosis in rats
Author(s) -
Kurebayashi Yoichi,
Honda Yuko
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840140323
Subject(s) - prostaglandin , medicine , endocrinology , prostaglandin e , prostaglandin e1 , antibody , necrosis , prostaglandin e2 , complement system , chemistry , biology , immunology
16,16‐Dimethyl prostaglandin E 2 , a known cytoprotective agent, was examined for its ability to protect the liver against complement‐mediated necrosis induced by an intravenous injection of a monoclonal antibody against a rat liver—specific antigen in rats. The hepatic injury induced by the antibody was characterized by (a) rapid development of numerous massive hemorrhagic foci of necrotic liver cells, (b) marked increases in serum liver enzyme activities and (c) pronounced reduction in the CH 50 level, presumably as a result of complement consumption in the liver. Pretreatment with 16,16‐dimethyl prostaglandin E 2 at intraperitoneal doses of 20 and 100 μg/kg suppressed the hepatic injury, as evidenced by markedly mitigated liver‐cell necrosis and much smaller increases in the serum‐enzyme activities compared with the values in diseased control animals. The prostaglandin analogue failed to prevent serum complement consumption in response to the antibody injection or affect the CH 50 level at the preinjury stage, indicating that neither complement inactivation nor interference with the antigen‐antibody reaction was involved in the hepatic protection. The hepatoprotective doses of 16,16‐dimethyl prostaglandin E 2 produced a significant increase in liver cyclic AMP content in a dose‐related manner. In addition, intravenous dibutyryl cyclic AMP at 3 and 10 mg/kg dose‐dependently prevented histological and biochemical changes in the hepatic damage without altering the rate of reduction in serum complement activity. Like 16,16‐dimethyl prostaglandin E 2 , dibutyryl cyclic AMP did not affect the preinjury CH 50 level. These results suggest that increased hepatocellular cyclic AMP is responsible, at least in part, for the hepatic protection afforded by 16,16‐dimethyl prostaglandin E 2 against the membrane‐damaging insult of activated complement, possibly through the stabilization of the plasma membrane.