İmikimod ile Oluşturulan Deneysel Modelde Loganinin Karaciğer İnflamasyonu ve NLRP3 İnflamazomu Üzerindeki Etkileri

Öz

Sistemik inflamasyon, oksidatif stres ve inflamazom sinyalleşmesi gibi doğuştan gelen bağışıklık mekanizmalarının aktivasyonu aracılığıyla karaciğer hasarına katkıda bulunmaktadır. NLRP3 inflamazomu, proinflamatuvar sitokinlerin olgunlaşmasını sağlayan ve inflamatuvar yanıtı amplifiye eden temel bir moleküler komplekstir. Doğal kaynaklı bir iridoid glikozit olan loganinin (LOG), antiinflamatuvar ve antioksidan etkiler gösterdiği bildirilmiş olmakla birlikte, imikimod (IMQ) ile indüklenen sistemik inflamasyon modelindeki hepatik etkileri henüz yeterince aydınlatılmamıştır. Bu çalışmada, IMQ ile indüklenen sistemik inflamasyon modelinde LOG’un hepatik inflamatuvar değişiklikler, kollajen birikimi ve NLRP3/ASC ile ilişkili inflamatuvar yanıtlar üzerindeki etkilerinin araştırılması amaçlandı. LOG (50 mg/kg/gün, deri altı) yedi gün boyunca günlük olarak uygulandı ve her uygulama ilgili günün IMQ uygulamasından önce gerçekleştirildi. Karaciğer dokusundaki histopatolojik değişiklikler hematoksilen-eozin (H&E) ve Masson trikrom boyamaları ile değerlendirildi. NLRP3 ve ASC protein ekspresyonları immünohistokimyasal yöntemlerle incelendi. Ayrıca, Tnf ve Nlrp3 genlerinin göreceli mRNA ekspresyon düzeyleri qPCR analizi ile belirlendi. IMQ uygulamasının hepatoselüler dejenerasyon, kollajen birikiminde artış ve NLRP3 ile ASC immünoreaktivitesinde belirgin yükselme ile ilişkili olduğu gözlendi. LOG uygulamasının ise inflamatuvar hücre infiltrasyonunu ve kollajen birikimini azalttığı, ayrıca daha düşük NLRP3 ve ASC ekspresyon düzeyleriyle ilişkili olduğu saptandı. Bu bulgular, IMQ ile indüklenen sistemik inflamasyon modelinde LOG uygulamasının, hepatik inflamatuvar değişikliklerin azalması ve NLRP3/ASC ile ilişkili inflamatuvar yanıtlardaki değişikliklerle potansiyel olarak ilişkili olabileceğini düşündürmektedir.

Anahtar Kelimeler

• İmikimod
• Loganin
• Hepatik inflamasyon
• Fibrozis
• NLRP3 inflamazomu.

Destekleyen Kurum

Van Yüzüncü Yıl Üniversitesi

Proje Numarası

TYL-2022-9889

Etik Beyan

Bu çalışmanın, özgün bir çalışma olduğunu; çalışmanın hazırlık, veri toplama, analiz ve bilgilerin sunumu olmak üzere tüm aşamalarından bilimsel etik ilke ve kurallarına uygun davrandığımı; bu çalışma kapsamında elde edilmeyen tüm veri ve bilgiler için kaynak gösterdiğimi ve bu kaynaklara kaynakçada yer verdiğimi; kullanılan verilerde herhangi bir değişiklik yapmadığımı, çalışmanın Committee on Publication Ethics (COPE)' in tüm şartlarını ve koşullarını kabul ederek etik görev ve sorumluluklara riayet ettiğimi beyan ederim. Herhangi bir zamanda, çalışmayla ilgili yaptığım bu beyana aykırı bir durumun saptanması durumunda, ortaya çıkacak tüm ahlaki ve hukuki sonuçlara razı olduğumu bildiririm.

Effects of Loganin on Hepatic Inflammation and the NLRP3 Inflammasome in an Imiquimod-Induced Experimental Model

Öz

Systemic inflammation leads to liver injury through oxidative stress and activation of innate immune pathways, including inflammasome signalling. NLRP3 inflammasome facilitates the maturation of inflammatory cytokines and amplifies inflammatory responses. Loganin (LOG), a naturally occurring iridoid glycoside, has been reported to possess anti-inflammatory and antioxidant properties; however, its effects on hepatic inflammation remain only partly understood in an imiquimod (IMQ)-induced inflammation model. This study aimed to evaluate the potential effects of LOG in the IMQ-induced systemic inflammation model, focusing on liver inflammatory changes, collagen deposition, and NLRP3/ASC- associated inflammatory responses. BALB/c mice were treated with topical IMQ to induce systemic inflammation. LOG (50 mg/kg/day, s.c.) was administered daily for seven days, and each administration was performed prior to the corresponding IMQ application. Histopathological changes were assessed using H&E and Masson’s trichrome staining. Immunohistochemistry was performed to determine NLRP3 and ASC expression in liver tissue. qPCR was used to measure the relative mRNA expression levels of Tnf and Nlrp3 in liver samples. IMQ was associated with hepatocellular alterations, increased collagen deposition, and higher immunoreactivity for NLRP3 and ASC. LOG reduced inflammatory infiltration and collagen accumulation, along with decreased expression of NLRP3 and ASC. These findings suggest that LOG administration may be associated with attenuated hepatic inflammatory alterations and changes in NLRP3/ASC-associated inflammatory responses in an IMQ-induced model of systemic inflammation.

Anahtar Kelimeler

• Imiquimod
• Loganin
• Hepatic inflammation
• Fibrosis
• NLRP3 inflammasome.

Destekleyen Kurum

Van Yuzuncu Yil University

Proje Numarası

TYL-2022-9889

Etik Beyan

This study is an original work; I have adhered to the principles and rules of scientific ethics throughout all stages of the study, including preparation, data collection, analysis, and presentation of information; I have cited all data and information not obtained within the scope of this study and included these sources in the references; I have not made any alterations to the data used, and I hereby declare that I have complied with all the terms and conditions of the Committee on Publication Ethics (COPE) and adhered to ethical duties and responsibilities. I hereby declare that, should any situation contrary to this declaration regarding the study be identified at any time, I accept all moral and legal consequences that may arise.

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