MYRICETIN REDUCES CISPLATIN-INDUCED LUNG INJURY BY REGULATING OXIDATIVE STRESS AND HYPOXIA INDUCIBLE FACTOR-1α LEVELS

Öz

Cisplatin is an anticancer agent that is frequently used in the treatment of solid tumors. However, widespread organ toxicity is the most important factor limiting its use. Lung toxicity has also become an increasing concern in recent years. This study aimed to evaluate the protective roles of myricetin, a natural antioxidant found in plants, in cisplatin-induced lung injury. For this purpose, twenty-eight male Wistar rats were randomly assigned to four equal groups (n=7): control, myricetin, cisplatin, and myricetin+cisplatin. The control group received physiological saline; the myricetin group was given myricetin (10 mg/kg) intraperitoneally for seven consecutive days. The cisplatin group was given a single dose of cisplatin (7.5 mg/kg) intraperitoneally on the seventh day. The myricetin+cisplatin group was treated with myricetin for seven consecutive days, and at the end of the seventh day, cisplatin was administered. One day later, the rats were sacrificed, and their lungs were removed. The sections obtained from the lungs were stained with hematoxylin & eosin, and histopathological damage was evaluated. Biochemical analyses were performed using total oxidant status, total antioxidant status, and hypoxia-inducible factor-1α. In results, significant inflammatory cell infiltration, cellular deterioration, and loss of tissue integrity were observed in the cisplatin group. In contrast, in the myricetin+cisplatin group, the cellular structure and alveolar order were largely preserved, and inflammatory infiltration was minimal. Pretreatment with myricetin reduced total oxidant status and hypoxia-inducible factor-1α while increasing total antioxidant status levels. Taken together, this study indicates that pretreatment of myricetin could serve therapeutic purposes in cisplatin-induced lung injury.

Anahtar Kelimeler

• Cisplatin
• HIF-1 alpha
• lung injury
• myricetin
• oxidative stress

MİRİSETİN OKSİDATİF STRESİ VE HİPOKSİ İNDÜKLENEBİLİR FAKTÖR-1α DÜZEYLERİNİ DÜZENLEYEREK SİSPLATİN KAYNAKLI AKCİĞER HASARINI AZALTIR

Öz

Sisplatin, katı tümörlerin tedavisinde sıklıkla kullanılan bir antikanser ajandır. Ancak yaygın organ toksisitesi kullanımını kısıtlayan en önemli faktördür. Akciğer toksisitesi de son yıllarda giderek artan bir endişe haline gelmiştir. Bu çalışmada bitkilerde bulunan doğal bir antioksidan olan mirisetinin sisplatin kaynaklı akciğer hasarında koruyucu rolünün değerlendirilmesi amaçlandı. Bu amaçla 28 adet erkek Wistar sıçanı rastgele dört eşit gruba (n=7) ayrıldı: kontrol, mirisetin, sisplatin ve mirisetin+sisplatin. Kontrol grubuna fizyolojik salin verildi; mirisetin grubuna artarda yedi gün boyunca periton içinden mirisetin (10 mg/kg) verildi. Sisplatin grubuna yedinci gün tek doz sisplatin (7.5 mg/kg) intraperitoneal olarak verildi. Mirisetin+sisplatin grubuna art arda yedi gün boyunca mirisetin tedavisi uygulandı ve yedinci günün sonunda sisplatin uygulandı. Bir gün sonra sıçanlar sakrifiye edildi ve akciğerleri çıkarıldı. Akciğerlerden alınan kesitler hematoksilen&eozin ile boyanarak histopatolojik hasar değerlendirildi. Biyokimyasal analizler toplam oksidan durumu, toplam antioksidan durumu ve hipoksi ile indüklenebilir faktör-1α kullanılarak yapıldı. Sonuç olarak sisplatin grubunda belirgin inflamatuar hücre infiltrasyonu, hücresel bozulma ve doku bütünlüğünde kayıp gözlendi. Buna karşılık mirisetin+sisplatin grubunda hücresel yapı ve alveoler düzen büyük ölçüde korunmuş, inflamatuar infiltrasyon ise minimal düzeyde kalmıştır. Mirisetin ile ön tedavi toplam oksidan statusu ve hipoksi ile indüklenebilir faktör-1α'yı azaltırken toplam antioksidan status seviyelerini arttırdı. Birlikte ele alındığında bu çalışma, mirisetin ön tedavisinin sisplatin kaynaklı akciğer hasarında terapötik amaçlara hizmet edebileceğini göstermektedir.

Anahtar Kelimeler

• Sisplatin
• HIF-1 alfa
• akciğer hasarı
• mirisetin
• oksidatif stress

Kaynakça

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