Antrodia cinnamomea, Doksorubisin Kaynaklı Kardiyotoksisitede Oksidatif Hasarı Azaltarak Kalp Histolojisini Koruyor

Öz

Doksorubisin (DOX) kardiyotoksisitesi oksidatif stres ile indüklenir ve miyokardiyal hasara yol açar. Bu çalışmada, Antrodia cinnamomea’nın DOX kaynaklı kalp hasarını azaltmadaki etkinliği değerlendirildi. Yirmi dört erkek Sprague-Dawley sıçanı rastgele dört gruba ayrıldı: Kontrol, DOX (2 mg/kg i.p., gün aşırı 10 gün), Antrodia cinnamomea (100 mg/kg p.o., günlük) ve DOX + Antrodia cinnamomea (2 mg/kg i.p., gün aşırı 10 gün ve 100 mg/kg p.o., günlük). Kalpler Hematoksilen-Eozin (H&E) ile boyandı ve yarı-kantitatif hasar skorlaması yapıldı. Sol ventrikül homojenatlarında malondialdehit (MDA), süperoksit dismutaz (SOD) ve indirgenmiş glutatyon (GSH) düzeyleri incelendi. DOX, miyokardda belirgin hasara, miyofibrillerin düzensizleşmesine, sitoplazmada vakuol oluşumuna, çekirdek morfolojisinde değişikliklere ve interstisyel ödem gelişimine yol açtı. Hasar skorları Kontrol grubuna kıyasla anlamlı derecede yüksekti (p <0.05). Biyokimyasal olarak DOX, MDA düzeylerini artırırken SOD ve GSH düzeylerini azalttı (p <0.05). Antrodia cinnamomea tek başına Kontrol grubuna benzer sonuçlar verdi. Eşzamanlı uygulama (DOX + Antrodia cinnamomea), DOX grubuna kıyasla MDA’yı anlamlı şekilde düşürdü ve SOD ile GSH düzeylerini kısmen geri kazandırdı (tümü p <0.05); bu bulgular daha düşük histopatoloji skorlarıyla tutarlıydı, ancak değerler tamamen Kontrol seviyelerine dönmedi. Sonuç olarak Antrodia cinnamomea, redoks dengesini iyileştirerek ve kalp kası yapısını koruyarak DOX kaynaklı kardiyotoksisiteyi hafifletmektedir. Bu sonuçlar, Antrodia cinnamomea’nın antrasiklin kardiyotoksisitesini azaltmada potansiyel bir yardımcı tedavi olduğunu desteklemekte ve apoptoz/iltihap belirteçleri, ultrastrüktürel doğrulama ve farmakokinetik profillemeyi içeren mekanistik ve translasyonel çalışmalara ihtiyaç olduğunu ortaya koymaktadır.

Anahtar Kelimeler

• Antrodia cinnamomea
• Doksorubisin
• Oksidatif stres
• Miyokard hasarı
• Kardiyotoksisite

Antrodia cinnamomea Reduces Oxidative Injury and Protects Cardiac Histology in Doxorubicin-Induced Cardiotoxicity

Öz

Doxorubicin (DOX) cardiotoxicity is induced by oxidative stress and results in myocardial damage. We assessed the efficacy of Antrodia cinnamomea in alleviating DOX-induced cardiac injury in rats. Twenty-four male Sprague-Dawley rats were randomly assigned to one of four groups: Control, DOX (2 mg/kg i.p., every other day for 10 days), Antrodia cinnamomea (100 mg/kg p.o., daily), or DOX + Antrodia cinnamomea (2 mg/kg i.p., every other day for 10 days and 100 mg/kg p.o., daily). H&E was used to look at the hearts and give them a semi-quantitative injury score. We investigated malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in left-ventricular homogenates. DOX caused a lot of damage to the heart muscle, disorganized myofibrils, created vacuoles in the cytoplasm, changed the shape of the nucleus, and caused interstitial edema. The injury scores were much higher than in the Control group (p <0.05). Biochemically, DOX elevated MDA levels while reducing SOD and GSH levels (p <0.05). Antrodia cinnamomea alone was similar to Control. Co-treatment (DOX + Antrodia cinnamomea) significantly reduced MDA and partially restored SOD and GSH in comparison to DOX (all p <0.05), which was consistent with lower histopathology scores; however, the values did not fully revert to Control levels. Antrodia cinnamomea lessens the cardiotoxicity caused by DOX by improving redox balance and protecting the structure of the heart muscle. These results support Antrodia cinnamomea as a potential adjunct to alleviate anthracycline cardiotoxicity and affirm the need for mechanistic and translational studies incorporating apoptosis/inflammation markers, ultrastructural validation, and pharmacokinetic profiling.

Anahtar Kelimeler

• Antrodia cinnamomea
• Doxorubicin
• Oxidative stress
• Myocardial injury
• Cardiotoxicity

Kaynakça

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