Publication: The effect of glucagon and cyclic adenosine monophosphate on acute liver damage induced by acetaminophen
Authors
Kelava, Tomislav ; Ćavar, Ivan ; Vukojevic, Katarina ; Saraga-Babić, Mirna ; Čulo, Filip
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
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.
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