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

Authors : Esra NURLU TEMEL, Şerife AĞIRCA TAŞAN, İlter İLHAN

Pages : 474-483

Doi:10.17343/sdutfd.1341730

View : 52 | Download : 34

Publication Date : 2023-09-23

Article Type : Research Paper

Abstract :Objective In septic conditions, hyperinflammatory response and hepatotoxicity are caused by oxidative stress, inflammation, and apoptosis. Irbesartan insert ignore into journalissuearticles values(IB);, an adrenergic receptor blocker, has anti-inflammatory and antioxidant properties. This study aimed to investigate the protective effect of IB on lipopolysaccharide insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(IP);]; and LPS + IB group [5 mg/kg LPS insert ignore into journalissuearticles values(IP); + 50 mg/kg IB insert ignore into journalissuearticles values(orally);]. After sacrification, tissues from the liver and blood were obtained for immunohistochemical and biochemical evaluations, such as interleukin-1 beta insert ignore into journalissuearticles values(IL-1β);, caspase-3 insert ignore into journalissuearticles values(Cas-3); alanine aminotransferase insert ignore into journalissuearticles values(ALT);, aspartate aminotransferase insert ignore into journalissuearticles values(AST);, oxidative stress index insert ignore into journalissuearticles values(OSI);, total oxidant status insert ignore into journalissuearticles values(TOS);, and total antioxidant status insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(p = 0.001);. IB also decreased AST and ALT values insert ignore into journalissuearticles values(p = 0.001);. In the IB group, Cas-3 and IL-1β levels were significantly decreased by IB administration insert ignore into journalissuearticles values(p = 0.001);. In addition, the IB ameliorated histopathological findings showed enhanced hyperaemia, haemorrhages, vacuolisation and significant neutrophilic leukocyte infiltration insert ignore into journalissuearticles values(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.
Keywords : Sepsis, irbesartan, inflamasyon, hepatotoksisite, oksidatif stres, apoptoz

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