Protective Potential of Morin in Ifosfamide-Induced Lung Toxicity: Modulation of Oxidative Stress, Inflammation and Apoptosis Parameters

Yıl 2025, Cilt: 20 Sayı: 1, 50 - 56, 29.04.2025

Özge Kandemir , Elif Dalkılınç

https://doi.org/10.17094/vetsci.1659052

Öz

In this study, the protective effect of morin against lung toxicity induced by ifosfamide (IFO), a widely used drug in cancer treatment, was investigated. Thirty-five male Sprague Dawley rats were divided into five groups: Control, Morin (200 mg/kg), IFO and two different Morin doses (IFO + Morin 100 mg/kg and IFO + Morin 200 mg/kg). Rats were given morin 100 mg/kg or 200 mg/kg for 2 days and on the second day, IFO 500 mg/kg was administered as a single dose. Biochemical and molecular methods analyzed oxidative stress, inflammation, autophagy and apoptosis markers. According to the data obtained, IFO increased malondialdehyde (MDA) levels in lung tissue, while decreasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) activities and glutathione (GSH) levels. However, it was observed that morin administration decreased MDA levels and increased GSH levels and GPx, SOD, CAT activities. IFO administration inhibited the expression of B-cell lymphoma-2 (Bcl-2) and the nuclear factor erythroid 2-related factor 2 (Nrf-2) /heme oxygenase-1 (HO-1) pathway, while increasing levels of nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), Bcl-2-associated x protein (Bax), and cysteine aspartate specific protease-3 (Caspase-3). However, Morin decreased NF-κB and iNOS levels and inhibited inflammation by activating the Nrf-2/HO-1 pathway and prevented apoptosis by decreasing Bax and Caspase-3 and increasing Bcl-2. It also caused a decrease in Beclin-1 levels. According to the findings, IFO by affecting various signaling pathways in lung tissue, causing cellular damage, while morin demonstrated protective qualities against this damage.

Anahtar Kelimeler

Apoptosis , Ifosfamide , Inflammation , Lung toxicity , Morin , Oxidative stress.

İfosfamid ile İndüklenen Akciğer Toksisitesinde Morin’in Koruyucu Potansiyeli: Oksidatif Stres, İnflamasyon ve Apoptoz Parametrelerinin Modülasyonu

Öz

Bu çalışmada, kanser tedavisinde yaygın olarak kullanılan bir ilaç olan İfosfamid (IFO)'in neden olduğu akciğer toksisitesine karşı morin’in koruyucu etkisi araştırıldı. Otuz beş erkek Sprague Dawley sıçanı beş gruba ayrıldı: Kontrol, Morin (200 mg/kg), IFO ve iki farklı Morin dozu (IFO + Morin 100 mg/kg ve IFO + Morin 200 mg/kg) uygulandı. Sıçanlara 2 gün boyunca Morin 100 mg/kg veya 200 mg/kg verildi ve ikinci gün IFO 500 mg/kg tek doz olarak uygulandı. Oksidatif stres, inflamasyon, otofaji ve apoptoz belirteçleri biyokimyasal ve moleküler yöntemlerle analiz edildi. Elde edilen verilere göre, IFO akciğer dokusunda malondialdehit (MDA) seviyelerini artırırken, süperoksit dismutaz (SOD), katalaz (KAT), glutatyon peroksidaz (GPx) aktiviteleri ve glutatyon (GSH) seviyelerini azalttı. Ancak morin uygulamasının MDA düzeyini azalttığı, GSH seviyeleri ve GPx, SOD, KAT aktivitelerini arttırdığı gözlemlendi. IFO uygulaması, B-hücreli lenfoma-2 (Bcl-2) ve nükleer faktör eritroid 2 ile ilişkili faktör 2 (Nrf-2) /hem oksijenaz-1 (HO-1) yolunun ekspresyonunu inhibe ederken, nükleer faktör-kappa B (NF-κB), indüklenebilir nitrik oksit sentaz (iNOS), Bcl-2 ile ilişkili x proteini (Bax) ve sistein aspartat spesifik proteaz-3 (Kaspaz-3) seviyelerini artırdı. Ancak morin NF-κB ve iNOS seviyelerini azalttı ve Nrf-2/HO-1 yolağını aktive ederek inflamasyonu inhibe etti ve Bax ve Kaspaz-3’ü azaltıp Bcl-2’yi artırarak apoptozu engelledi. Ayrıca Beklin-1 düzeylerinde azalmaya neden oldu. Bulgulara göre, IFO akciğer dokusunda çeşitli sinyal yollarını etkileyerek hücresel hasara neden olurken, morin bu hasara karşı koruyucu özellik gösterdi.

Anahtar Kelimeler

Akciğer toksisitesi , Apoptoz , İfosfamid , İnflamasyon , Morin , Oksidatif stres.

Kaynakça

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