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Medical Journal of Süleyman Demirel University

2602-2109

Süleyman Demirel Üniversitesi

10.17343/sdutfd.1341730

Infectious Diseases

Bulaşıcı Hastalıklar

İRBESARTAN LİPOPOLİSAKARİT TARAFINDAN İNDÜKLENEN KARACİĞER HASARINI, TOPLAM OKSİDAN DURUMU, İNTERLÖKİN-1B VE KASPAZ-3 SEVİYELERİNİN İNHİBİSYONU YOLUYLA AZALTIR

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

https://orcid.org/0000-0003-4618-168X

Nurlu Temel

Esra

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

https://orcid.org/0000-0002-1469-3464

Ağırca Taşan

Şerife

MEHMET AKİF ERSOY ÜNİVERSİTESİ, VETERİNER FAKÜLTESİ

https://orcid.org/0000-0003-3739-9580

İlhan

İlter

SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ

09 23 2023

30 3 474 483 08 11 2023 08 27 2023

1994

Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

AmaçSeptik koşullarda hiperinflamatuar yanıta ve hepatotoksisiteye;oksidatif stres, inflamasyon ve apoptoz nedenolur. Bir adrenerjik reseptör blokeri olan irbesartan(IB), antiinflamatuar ve antioksidan özelliklere sahiptir.Bu çalışmada, IB'nin lipopolisakkarit (LPS) kaynaklıakut hepatotoksisite üzerindeki koruyucu etkisininaraştırılması amaçlandı.Gereç ve YöntemÜç grupta toplam sekiz sıçan kullanıldı; kontrol grubu,LPS grubu [5 mg/kg, intraperitoneal (IP)]; ve LPS+ IB grubu [5 mg/kg LPS (IP) + 50 mg/kg IB (oral)].Sakrifikasyondan sonra interlökin-1 beta (IL-1β), kaspaz-3 (Cas-3) alanin aminotransferaz (ALT), aspartataminotransferaz (AST), oksidatif stres indeksi (OSI),toplam oksidan durumu (TOS) ve toplam antioksidandurumu (TAS) gibi immünohistokimyasal ve biyokimyasaldeğerlendirmeler için karaciğer ve kandan dokularalındı.BulgularKontrol grubuyla karşılaştırıldığında kanda AST ve ALTdüzeylerinde artış, biyokimyasal olarak dokuda TOSve OSI düzeyinde artış ve TAS düzeyinde azalma,immünohistokimyasal olarak IL-1β, Cas-3 düzeyindeartış tespit edildi. Ayrıca LPS grubunda karaciğer dokusundahistopatolojik olarak hiperemi, kanama, vakuolizasyonve belirgin nötrofil infiltrasyonu saptandı. IBtüm bu bulguları tersine çevirdi. IB uygulaması ile TASseviyeleri yükselirken, TOS ve OSI seviyeleri azaldı (p= 0.001). IB ayrıca AST ve ALT değerlerini de düşürdü(p = 0.001). IB grubunda, Cas-3 ve IL-1β seviyeleri, IBuygulamasıyla önemli ölçüde azaldı (p = 0.001). Ekolarak, IB, artmış hiperemi, kanama, vakuolizasyon veönemli nötrofilik lökosit infiltrasyon gibi histopatolojikbulguları iyileştirdi (p = 0.001). IB tedavisi, antioksidan,antienflamatuar ve antiapoptotik özellikleriyle LPS'ninneden olduğu hepatotoksisiteyi zayıflattı.SonuçKaraciğer hasarını hafifletmek ve karaciğer fonksiyonunueski haline getirmek sepsisli hastalarda morbi-dite ve mortalite oranlarını düşürür. IB, antioksidan,antiinflamatuar ve antiapoptotik özellikleri sayesindekaraciğer dokusunu LPS'nin neden olduğu hepatotoksisitedenkorur. Karaciğerin sepsisteki rolünün dahafazla araştırılması, yeni terapötik hedeflerin ve stratejileringeliştirilmesine yol açabilir. IB, sepsis sırasındaakut hepatotoksisitenin önlenmesi için alternatif bir terapötikajan olabilir.

ObjectiveIn septic conditions, hyperinflammatory responseand hepatotoxicity are caused by oxidative stress,inflammation, and apoptosis. Irbesartan (IB), anadrenergic receptor blocker, has anti-inflammatory andantioxidant properties. This study aimed to investigatethe protective effect of IB on lipopolysaccharide (LPS)-induced acute hepatotoxicity.Material and MethodA total of eight rats were used in three groups; a controlgroup; 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 andblood were obtained for immunohistochemical andbiochemical evaluations, such as interleukin-1 beta(IL-1β), caspase-3 (Cas-3) alanine aminotransferase(ALT), aspartate aminotransferase (AST), oxidativestress index (OSI), total oxidant status (TOS), andtotal antioxidant status (TAS).ResultsCompared with the control group, increased ASTand ALT levels in the blood, biochemically increasedTOS and OSI and decreased TAS levels in thetissue, immunohistochemically increased IL-1β, Cas-3, detected. Also, in liver tissue, histopathologicallyhyperemia, hemorrhage, vacuolization, andsignificant neutrophilia infiltration were found in theLPS group. IB administration significantly reversedall these parameters. TAS levels were increasedby IB administration, whereas TOS and OSI levelswere decreased (p = 0.001). IB also decreasedAST and ALT values (p = 0.001). In the IB group,Cas-3 and IL-1β levels were significantly decreasedby IB administration (p = 0.001). In addition, theIB ameliorated histopathological findings showedenhanced hyperaemia, haemorrhages, vacuolisationand significant neutrophilic leukocyte infiltration(p = 0.001). IB treatment attenuated LPS-inducedhepatotoxicity by its antioxidant, anti-inflammatory andantiapoptotic properties.ConclusionAttenuating liver injury and restoring liver function lowersmorbidity and mortality rates in patients with sepsis.IB protects liver tissue from hepatotoxicity caused byLPS thanks to its antioxidant, anti-inflammatory, andanti-apoptotic properties. Further investigation of theliver’s role in sepsis may lead to the development ofnew therapeutic targets and strategies. IB may bean alternative therapeutic agent for the prevention ofacute hepatotoxicity during sepsis.

Apoptosis Hepatotoxicity Irbesartan Inflammation Oxidative stress Sepsis

Sepsis irbesartan inflamasyon hepatotoksisite oksidatif stres apoptoz

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