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The effect of glucagon and cyclic adenosine monophosphate on acute liver damage induced by acetaminophen

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dc.contributor.authorKelava, Tomislav
dc.contributor.authorĆavar, Ivan
dc.contributor.authorVukojevic, Katarina
dc.contributor.authorSaraga-Babić, Mirna
dc.contributor.authorČulo, Filip
dc.date.accessioned2018-02-19T11:11:28Z
dc.date.available2018-02-19T11:11:28Z
dc.date.issued2013
dc.description.abstractRecent 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.es
dc.formatapplication/pdfes
dc.format.extent11es
dc.identifier.citationHistology and Histopathology, vol. 28, nº 2, (2013)
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/56232
dc.languageenges
dc.publisherF. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histologíaes
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectGlucagones
dc.subjectcAMPes
dc.subjectAcetaminophenes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicinaes
dc.titleThe effect of glucagon and cyclic adenosine monophosphate on acute liver damage induced by acetaminophenes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.28, nº 2 (2013)