Investigation of The Effects of Carvacrol on Lambda-Cyhalothrin-Induced Gastrointestinal Injury in Rats: Modulation of Apoptosis and Endoplasmic Reticulum Stress Pathways

Abstract

This study investigated the mechanisms associated with oxidative stress, apoptosis, and endoplasmic reticulum (ER) stress in gastrointestinal damage induced by lambda-cyhalothrin (λ-CHL) in rats and evaluated the protective effects of carvacrol (CRV) against this toxicity. Rats were divided into five groups: control, CRV, λ-CHL, λ-CHL+CRV25, and λ-CHL+CRV50, and treatments were administered orally for 21 days. In the λ-CHL group, malondialdehyde (MDA) levels significantly increased, whereas glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione (GSH) levels decreased (p<0.001). Additionally, apoptotic signaling pathways were activated by a pro-apoptotic shift in the Bcl2-associated X protein (Bax)/ B-cell lymphoma 2 (Bcl2) ratio and increased Casp3 activation (p<0.001). Moreover, endoplasmic reticulum (ER) stress markers, including activating transcription factor 6 (Atf6), C/EBP homologous protein (Chop), and protein kinase RNA-like endoplasmic reticulum kinase (Perk), were significantly elevated (p<0.001). In the CRV-treated groups, particularly in the λ-CHL+CRV50 group, MDA levels were significantly suppressed (p<0.001), while antioxidant defense parameters such as GPx, SOD activity, and GSH levels were significantly increased (p<0.001). Furthermore, Bcl2 was elevated, whereas Bax, Casp3, and ER stress markers were significantly reduced (p<0.001). CRV alone showed patterns similar to the control group. In conclusion, λ-CHL induces gastrointestinal damage through multiple molecular mechanisms involving oxidative stress, apoptosis, and ER stress, whereas CRV exhibits a dose-dependent protective effect against this toxicity.

Keywords

• Carvacrol
• Endoplasmic reticulum stress
• Gastrointestinal injury
• Lambda-cyhalothrin
• Oxidative stress

Ethical Statement

Bu çalışma, Atatürk Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’nun 25.02.2026 tarih ve 2026/2 sayılı, 8 nolu kararı ile onaylanmış olup, tüm deneysel uygulamalar ulusal ve uluslararası etik kurallar çerçevesinde gerçekleştirilmiştir.

Sıçanlarda Lambda-Sihalotrin Kaynaklı Gastrointestinal Hasar Üzerine Karvakrol’ün Etkilerinin İncelenmesi: Apoptoz ve Endoplazmik Retikulum Stresi Yolaklarının Düzenlenmesi

Abstract

Bu çalışmada, sentetik bir Tip II piretroid olan lambda-sihalotrinin (λ-SHL) sıçanlarda oluşturduğu gastrointestinal hasarın oksidatif stres, apoptoz ve endoplazmik retikulum (ER) stresi ile ilişkili mekanizmaları araştırılmış ve karvakrolün (KRV) bu toksisiteye karşı koruyucu etkileri değerlendirilmiştir. Erkek Sprague-Dawley sıçanlar; sağlıklı kontrol, KRV, λ-SHL, λ-SHL+KRV25 ve λ-SHL+KRV50 olmak üzere beş gruba ayrılarak 21 gün süreyle oral yolla uygulanmıştır. λ-SHL grubunda mide ve bağırsak dokularında malondialdehit (MDA) düzeylerinin anlamlı şekilde arttığı, glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD) aktivitesi ve glutatyon (GSH) düzeylerinin ise belirgin olarak azaldığı saptanmıştır (p<0.001). Aynı grupta apoptotik sinyal yolaklarında Bcl2 ile ilişkili X proteini (Bax)/ B-hücreli lenfoma 2 (Bcl2) oranının pro-apoptotik yönde değiştiği ve Casp3 aktivasyonunun yükseldiği belirlenmiştir (p<0.001). Ayrıca endoplazmik retikulum (ER) stresi belirteçleri olan aktive edici transkripsiyon faktörü 6 (Atf6), C/EBP homolog proteini (Chop) ve protein kinaz RNA benzeri endoplazmik retikulum kinazı (Perk) gen ekspresyonlarının anlamlı düzeyde arttığı gözlenmiştir (p<0.001). KRV uygulanan gruplarda, özellikle yüksek doz KRV verilen λ-SHL+KRV50 grubunda, oksidatif stres parametrelerinin bir göstergesi olan MDA seviyelerinin baskılandığı (p<0.001), antioksidan savunma parametrelerinden olan GPx, SOD aktiviteleri ve GSH seviyelerinin ise arttığı tespit edilmiştir (p<0.001). Apoptoz belirteçlerinden olan Bcl2 gen ekspresyon düzeyinin arttığı, Bax ve Casp3 gen ekspresyon seviyeleri ile ER stresi belirteçlerinin anlamlı şekilde gerilediği tespit edilmiştir (p<0.001). Sadece KRV verilen gruplarda ise incelenen parametreler kontrol ve tedavi gruplarına paralel şekilde seyretmiştir. Sonuç olarak, λ-SHL’nin gastrointestinal dokuda çoklu moleküler mekanizmalar üzerinden hasara yol açtığı, KRV’nin ise bu toksisiteye karşı belirgin ve doza bağlı koruyucu etki gösterdiği ortaya konmuştur.

Keywords

• Endoplazmik retikulum stresi
• Gastrointestinal hasar
• Karvakrol
• Lambda-sihalotrin
• Oksidatif stres

Ethical Statement

Bu çalışma, Atatürk Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu’nun 25.02.2026 tarih ve 2026/2 sayılı, 8 nolu kararı ile onaylanmış olup, tüm deneysel uygulamalar ulusal ve uluslararası etik kurallar çerçevesinde gerçekleştirilmiştir.

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