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The effect of glucagon and cyclic adenosine monophosphate on acute liver damage induced by acetaminophen.
MedLine Citation:
PMID:  23275307     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Recent investigations suggest that glucagon might have a potentially important hepatoprotective activity. We investigated the effect of glucagon in a model of acetaminophen-induced liver injury. CBA male mice were injected intraperitoneally with a lethal (300 mg/kg) or sublethal (150 mg/kg) dose of acetaminophen. The liver injury was assessed by observing the survival of mice, by liver histology and by measuring the concentration of alanine-aminotransferase (ALT). Inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB) protein expressions were determined immunohistochemically. Hepatic levels of reduced glutathione (GSH) and cyclic adenosine monophosphate (cAMP) were also measured. Results show that glucagon, dose and time dependently, protects against acetaminophen-induced hepatotoxicity. This protection was achieved with a dose of 0.5 mg/kg of glucagon given intraperitoneally 15 min before or 1 h after acetaminophen. Treatment of animals with acetaminophen elevated ALT and nitrite/nitrate concentration in the plasma, enhanced iNOS and NF-κB expression and reduced GSH and cAMP concentration in the liver. Animals treated with glucagon had higher hepatic cAMP level, lower ALT and nitrite/nitrate concentration in plasma and lower expression of iNOS in liver cells than animals in control group, whereas there was no difference in the expression of NF-κB. Glucagon did not prevent the loss of GSH content caused by acetaminophen. Our investigation indicates that glucagon has a moderately protective effect against acetaminophen-induced liver injury, which is, at least partially, mediated through the downregulation of iNOS and through the increase in hepatic cAMP content, but it is not mediated through the modulation of NF-κB activity.
Authors:
T Kelava; I Cavar; K Vukojevic; M Saraga-Babic; F Culo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Histology and histopathology     Volume:  28     ISSN:  1699-5848     ISO Abbreviation:  Histol. Histopathol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8609357     Medline TA:  Histol Histopathol     Country:  Spain    
Other Details:
Languages:  eng     Pagination:  245-55     Citation Subset:  IM    
Affiliation:
Department of Physiology, School of Medicine, University of Zagreb, Croatia. tkelava@mef.hr.
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