An Evaluation of Damages Caused by Doxorubicin in Liver Tissue and Potential Protective Effect of Propolis on These Damages

Abstract

Objective: Doxorubicin (DOX), one of the chemotherapeutic drugs utilized in cancer treatment, has limited clinical use due to its serious toxic effects on non-target organs. The purpose of this study is to reveal the harmful effects of DOX in rat liver and the possible protective effect of propolis (PRPLS), a mixture of various herbal products collected by honeybees, on these damages by Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy. Methods: Sprague dawley rats were separated into 4 groups; control, DOX (cumulative dose: 15 mg/kg), PRPLS (200 mg/kg) and DOX + PRPLS. The rats were given 200 mg/kg PRPLS by oral gavage daily for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on days 10, 12, 14, 16, 18 and 20 of the experiment. 24 hrs after the last administrations, liver samples were collected and examined by ATR-FTIR spectroscopy. Results: DOX caused a decrease in the amount of glycogen and nucleic acids, an increase in the amount of lipids and proteins and some important changes in the metabolism, structure and conformation of these molecules in the liver. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane order and protein denaturation. PRPLS did not induce any toxic effect on the liver when it was given alone and PRPLS administered before DOX was not effective to eliminate these harmful effects of DOX. Conclusions: DOX caused significant structural and compositional changes in liver tissue and PRPLS was inadequate to prevent these changes at the dose and time used here.

Keywords

• Doxorubicin
• propolis
• ATR-FTIR spectroscopy
• liver
• chemotherapy

Doksorubisinin Karaciğer Dokusunda Oluşturduğu Hasarın ve Propolisin Bu Hasar Üzerindeki Potansiyel Koruyucu Etkisinin Değerlendirilmesi

Abstract

Amaç: Kanser tedavisinde kullanılan kemoterapötik ilaçlardan birisi olan doksorubisin (DOX), hedef dışı organlar üzerindeki ciddi toksik etkileri nedeniyle sınırlı klinik kullanıma sahiptir. Bu çalışmanın amacı, DOX'un sıçan karaciğerindeki zararlı etkilerini ve bal arıları tarafından toplanan çeşitli bitkisel ürünlerin bir karışımı olan propolis (PRPLS)'in bu zararlar üzerindeki olası koruyucu etkisini Azaltılmış Toplam Yansıma-Fourier Dönüşüm Kızılötesi (ATR-FTIR) spektroskopisi ile ortaya çıkarmaktır. Gereç ve Yöntem: Sprague dawley sıçanlar 4 gruba ayrılmıştır; kontrol, DOX (kümülatif doz: 15 mg/kg), PRPLS (200 mg/kg) ve DOX + PRPLS. Sıçanlara ardışık 20 gün boyunca oral gavaj yoluyla günlük 200 mg/kg PRPLS ve 10, 12, 14, 16, 18 ve 20. günlerde intraperitoneal olarak 2,5 mg/kg DOX verilmiştir. Son uygulamalardan 24 saat sonra karaciğer örnekleri alınmış ve ATR-FTIR spektroskopisi ile incelenmiştir. Bulgular: DOX karaciğerde glikojen ve nükleik asit miktarında azalmaya, lipid ve protein miktarında artışa ve bu moleküllerin metabolizması, yapısı ve konformasyonlarında bazı önemli değişikliklere sebep olmuştur. DOX, ayrıca lipid peroksidasyonuna, membran akışkanlığında bir artışa, membran düzeninde bir azalmaya ve protein denatürasyonuna neden olmuştur. PRPLS tek başına verildiğinde karaciğer üzerinde herhangi bir toksik etki oluşturmamış ve DOX'tan önce verilen PRPLS, DOX'un zararlı etkilerini ortadan kaldırmada etkili olamamıştır. Sonuç: DOX, karaciğer dokusunda önemli yapısal ve kompozisyonel değişikliklere neden olmuş ve PRPLS bu çalışmada kullanılan doz ve zamanda bu değişiklikleri önlemekte yetersiz kalmıştır.

Keywords

• Doksorubisin
• Propolis
• ATR-FTIR Spektroskopisi
• Karaciğer
• Kemoterapi

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