Doksorubisinin karaciğerde meydana getirdiği hasarın ve bu hasara karşı propolisin olası koruyucu etkisinin moleküler düzeyde incelenmesi
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Dosyalar
Tarih
2022
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Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Birçok kanserin tedavisinde yaygın olarak kullanılan kemoterapötik bir ajan olan doksorubisin (DOX), hedef dışı organlarda ciddi toksik etkilere sebep olmaktadır. Bu çalışmanın amacı, DOX'un sıçan karaciğer ve kan dokularında meydana getirdiği zararlı etkileri ve bu hasar üzerinde güçlü antioksidan maddeler içeren bir arı ürünü olan propolis (PRPLS)'in olası koruyucu etkisini Azaltılmış Toplam Yansıma-Fourier Dönüşüm Kızılötesi (ATR-FTIR) spektroskopisi ve biyokimyasal testler ile moleküler düzeyde ortaya çıkarmaktır. Bu amaç doğrultusunda, erkek Sprague dawley sıçanlar 4 farklı gruba ayrılmıştır; kontrol (n=7), DOX (2,5 mg/kg'lık 6 enjeksiyon, kümülatif doz: 15 mg/kg; n=7), PRPLS (200 mg/kg, günlük; n=6) ve DOX + PRPLS (15 mg/kg, kümülatif; 200 mg/kg, günlük, sırasıyla; n=7). Sıçanlara 20 gün boyunca her gün 200 mg/kg PRPLS oral gavaj yöntemi ile 2,5 mg/kg DOX 10., 12., 14., 16., 18. ve 20. günlerde intraperitonel olarak verilmiştir. Deneyin 21. günü hayvanlardan karaciğer ve kan örnekleri alınmış, karaciğer dokuları ATR-FTIR spektroskopisi ile incelenmiş, kan plazma örneklerinde total antioksidan seviyesi (TAS) ve total oksidan seviyesi (TOS) ölçülmüş ve oksidatif stres indeksi (OSI) hesaplanmıştır. Sonuçlar DOX'un karaciğerde glikojen ve nükleik asit miktarında azalmaya, lipid ve protein miktarında artışa ve bu moleküllerin metabolizmasında, yapısında ve konformasyonunda bazı önemli değişikliklere sebep olduğunu göstermiştir. DOX ayrıca lipid peroksidasyonuna, membran akışkanlığında bir artışa, membran düzeninde bir azalmaya ve protein denatürasyonuna neden olmuştur. TAS ve TOS deney sonuçları, DOX'un kan dokusunda oksidatif stres yarattığını göstermiştir. PRPLS tek başına verildiğinde karaciğerde herhangi bir toksik etkiye sebep olmamış ancak kanın TAS miktarını artırarak organizmaya fayda sağlamıştır. DOX'tan önce verilen PRPLS DOX'un kanda yarattığı oksidatif stresi önlemiş ancak karaciğer dokusundaki biyomoleküllerde yarattığı zararlı etkilere karşı yeterli koruyucu etki gösterememiştir. Bu çalışma, DOX'un karaciğer ve kan dokularında önemli derecede hasar oluşturduğunu ve PRPLS'nin burada uygulanan doz ve zamanda kandaki oksidatif stresi önlediğini fakat karaciğer dokusunda bu hasarı önlemede yetersiz olduğunu göstermiştir.
Doxorubicin (DOX), a chemotherapeutic agent widely used in the treatment of many cancers, causes serious toxic effects in non-target organs. The aim of this study is to examine the harmful effects of DOX on the rat liver and blood tissues and the possible protective effect of propolis (PRPLS), a bee product containing strong antioxidant substances, on these damage at the molecular level with Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy and biochemical tests. For this purpose, male Sprague Dawley rats were divided into 4 groups; control (n=7), DOX (2.5 mg/kg in six injections; cumulative dose: 15 mg/kg; n=7), PRPLS (200 mg/kg, daily; n=6) and DOX + PRPLS (15 mg/kg, cumulatively; 200 mg/kg, daily; respectively; n=7). The rats were given 200 mg/kg PRPLS by oral gavage every day for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on the 10th, 12th,14th,16th, 18th and 20th day of the experiment. On the 21st day of the experiment liver and blood samples were collected, the liver tissues were examined by ATR-FTIR spectroscopy, total antioxidant level (TAS) and total oxidant level (TOS) were measured in blood plasma samples obtained from animals and oxidative stress index (OSI) was calculated. The results showed that DOX caused a decrease in the amount of glycogen and nucleic acid, an increase in the amount of lipid and protein and some important changes in the metabolism, structure and conformation of these molecules in the liver. It also induced lipid peroxidation, a decrease in membrane order and an increase in membrane dynamics. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane alignment, and protein denaturation. The results of TAS and TOS experiments showed that DOX induces oxidative stress in the blood tissue. When PRPLS was given alone, it did not cause any toxic effects in the liver but it benefited the organism by increasing the amount of TAS in the blood. PRPLS administered before DOX, prevented the oxidative stress induced by DOX in the blood however, it was not able toshow a protective effect against the harmful effects of DOX on biomolecules in the liver. This study revealed that DOX causes significant damage to liver and blood tissues, and PRPLS at the dose and time administered here prevents oxidative stress in the blood but is insufficient to prevent this damage in liver tissue.
Doxorubicin (DOX), a chemotherapeutic agent widely used in the treatment of many cancers, causes serious toxic effects in non-target organs. The aim of this study is to examine the harmful effects of DOX on the rat liver and blood tissues and the possible protective effect of propolis (PRPLS), a bee product containing strong antioxidant substances, on these damage at the molecular level with Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy and biochemical tests. For this purpose, male Sprague Dawley rats were divided into 4 groups; control (n=7), DOX (2.5 mg/kg in six injections; cumulative dose: 15 mg/kg; n=7), PRPLS (200 mg/kg, daily; n=6) and DOX + PRPLS (15 mg/kg, cumulatively; 200 mg/kg, daily; respectively; n=7). The rats were given 200 mg/kg PRPLS by oral gavage every day for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on the 10th, 12th,14th,16th, 18th and 20th day of the experiment. On the 21st day of the experiment liver and blood samples were collected, the liver tissues were examined by ATR-FTIR spectroscopy, total antioxidant level (TAS) and total oxidant level (TOS) were measured in blood plasma samples obtained from animals and oxidative stress index (OSI) was calculated. The results showed that DOX caused a decrease in the amount of glycogen and nucleic acid, an increase in the amount of lipid and protein and some important changes in the metabolism, structure and conformation of these molecules in the liver. It also induced lipid peroxidation, a decrease in membrane order and an increase in membrane dynamics. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane alignment, and protein denaturation. The results of TAS and TOS experiments showed that DOX induces oxidative stress in the blood tissue. When PRPLS was given alone, it did not cause any toxic effects in the liver but it benefited the organism by increasing the amount of TAS in the blood. PRPLS administered before DOX, prevented the oxidative stress induced by DOX in the blood however, it was not able toshow a protective effect against the harmful effects of DOX on biomolecules in the liver. This study revealed that DOX causes significant damage to liver and blood tissues, and PRPLS at the dose and time administered here prevents oxidative stress in the blood but is insufficient to prevent this damage in liver tissue.
Açıklama
Anahtar Kelimeler
Biyofizik, Biophysics, Biyokimya, Biochemistry, Moleküler Tıp, Molecular Medicine