Objective
In septic conditions, hyperinflammatory response
and hepatotoxicity are caused by oxidative stress,
inflammation, and apoptosis. Irbesartan (IB), an
adrenergic receptor blocker, has anti-inflammatory and
antioxidant properties. This study aimed to investigate
the protective effect of IB on lipopolysaccharide (LPS)-
induced acute hepatotoxicity.
Material and Method
A total of eight rats were used in three groups; a control
group; LPS group [5 mg/kg, intraperitoneally (IP)];
and LPS + IB group [5 mg/kg LPS (IP) + 50 mg/kg IB
(orally)]. After sacrification, tissues from the liver and
blood were obtained for immunohistochemical and
biochemical evaluations, such as interleukin-1 beta
(IL-1β), caspase-3 (Cas-3) alanine aminotransferase
(ALT), aspartate aminotransferase (AST), oxidative
stress index (OSI), total oxidant status (TOS), and
total antioxidant status (TAS).
Results
Compared with the control group, increased AST
and ALT levels in the blood, biochemically increased
TOS and OSI and decreased TAS levels in the
tissue, immunohistochemically increased IL-1β, Cas-
3, detected. Also, in liver tissue, histopathologically
hyperemia, hemorrhage, vacuolization, and
significant neutrophilia infiltration were found in the
LPS group. IB administration significantly reversed
all these parameters. TAS levels were increased
by IB administration, whereas TOS and OSI levels
were decreased (p = 0.001). IB also decreased
AST and ALT values (p = 0.001). In the IB group,
Cas-3 and IL-1β levels were significantly decreased
by IB administration (p = 0.001). In addition, the
IB ameliorated histopathological findings showed
enhanced hyperaemia, haemorrhages, vacuolisation
and significant neutrophilic leukocyte infiltration
(p = 0.001). IB treatment attenuated LPS-induced
hepatotoxicity by its antioxidant, anti-inflammatory and
antiapoptotic properties.
Conclusion
Attenuating liver injury and restoring liver function lowers
morbidity and mortality rates in patients with sepsis.
IB protects liver tissue from hepatotoxicity caused by
LPS thanks to its antioxidant, anti-inflammatory, and
anti-apoptotic properties. Further investigation of the
liver’s role in sepsis may lead to the development of
new therapeutic targets and strategies. IB may be
an alternative therapeutic agent for the prevention of
acute hepatotoxicity during sepsis.
