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Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo
Author(s) -
Relja B,
Höhn C,
Bormann F,
Seyboth K,
Henrich D,
Marzi I,
Lehnert M
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01595.x
Subject(s) - proinflammatory cytokine , resuscitation , ethanol , liver injury , saline , alcoholic liver disease , medicine , in vivo , pathophysiology , inflammation , alcohol , tumor necrosis factor alpha , endocrinology , pharmacology , chemistry , anesthesia , biology , biochemistry , cirrhosis , microbiology and biotechnology
BACKGROUND AND PURPOSE Haemorrhagic shock and resuscitation (H/R) induces hepatic injury, strong inflammatory changes and death. Alcohol intoxication is assumed to worsen pathophysiological derangements after H/R. Here, we studied the effects of acute alcohol intoxication on survival, liver injury and inflammation after H/R, in rats. EXPERIMENTAL APPROACH Rats were given a single oral dose of ethanol (5 g·kg −1 , 30%) or saline (control), 12 h before they were haemorrhaged for 60 min and resuscitated (H/R). Sham groups received the same procedures without H/R. Measurements were made 2, 24 and 72 h after resuscitation. Survival was assessed 72 h after H/R. KEY RESULTS Ethanol increased survival after H/R three‐fold and also induced fatty changes in the liver. H/R‐induced liver injury was amplified by ethanol at 2 h but inhibited 24 h after H/R. Elevated serum IL‐6 levels as well as hepatic IL‐6 and TNF‐α gene expression 2 h after H/R were reduced by ethanol. Ethanol enhanced serum IL‐1β at 2 h, but did not affect increased hepatic IL‐1β expression at 72 h after H/R. Local inflammatory markers, hepatic infiltration with polymorphonuclear leukocytes and intercellular adhesion molecule 1 expression decreased after ethanol compared with saline, following H/R. Ethanol reduced H/R‐induced IκBα activation 2 h after H/R, and NF‐κB‐dependent gene expression of MMP9. CONCLUSIONS AND IMPLICATIONS Ethanol reduced H/R‐induced mortality at 72 h, accompanied by a suppression of proinflammatory changes after H/R in ethanol‐treated animals. Binge‐like ethanol exposure modulated the inflammatory response after H/R, an effect that was associated with NF‐κB activity.