IRBESARTAN REDUCES LIVER DAMAGE INDUCED BY LIPOPOLYSACCHARIDE VIA INHIBITION OF TOTAL OXIDANT STATUS, INTERLEUKIN-1B AND CASPASE-3 LEVELS

Abstract

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.