Compensatory hepatic regeneration after mild, but not fulminant, intraperitoneal sepsis in rats

Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not...

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Published inAmerican journal of physiology: Gastrointestinal and liver physiology Vol. 280; no. 5; pp. G968 - G973
Main Authors Weiss, Y G, Bellin, L, Kim, P K, Andrejko, K M, Haaxma, C A, Raj, N, Furth, E E, Deutschman, C S
Format Journal Article
LanguageEnglish
Published United States 01.05.2001
Subjects
Activating Transcription Factor 3
Animals
Apoptosis
Biomarkers - analysis
Cecum
Cyclin D1 - genetics
DNA-Binding Proteins - genetics
Glutathione Transferase - blood
In Situ Nick-End Labeling
Liver - pathology
Liver - physiopathology
Liver Regeneration
Male
Necrosis
Proto-Oncogene Proteins c-jun - genetics
Rats
Rats, Sprague-Dawley
RNA, Messenger - analysis
Sepsis - physiopathology
Time Factors
Transcription, Genetic
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Summary:Sepsis is the leading cause of death in surgical intensive care units. Although both mild sepsis secondary to cecal ligation and single puncture (CLP) and fulminant, double puncture CLP (2CLP) may provoke hepatocyte death, we hypothesize that regeneration compensates for cell death after CLP but not 2CLP. In male Sprague-Dawley rats, hepatic necrosis, as determined by serum alpha-glutathione S-transferase (alpha-GST) levels, was significantly but equally elevated over time after both CLP and 2CLP. Apoptosis, evaluated using both terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and morphological examination, was minimal after both CLP and 2CLP. Regeneration, assayed by staining tissue for incorporation of exogenously administered bromodeoxyuridine, was present after CLP but not after 2CLP. To further substantiate impaired regeneration, steady-state levels of mRNAs encoding JunB, LRF-1, and cyclin D1 were determined. After 2CLP, the absence of JunB, LRF-1, and cyclin D1 mRNAs confirmed failed activation of the mitogen-activated protein kinase-linked proliferative pathway and progression through the cell cycle. Therefore, failed hepatocyte regeneration may be a manifestation of hepatic dysfunction in fulminant sepsis.
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ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.280.5.g968