Cucumis melo var. agrestis Naudin'in sıçanlarda doksorubisin kaynaklı kardiyotoksisite üzerine etkisi

Year 2024, Volume: 49 Issue: 2, 353 - 362, 30.06.2024

Emine Sarman

https://doi.org/10.17826/cumj.1429969

Abstract

Amaç: Kemoterapötik bir antibiyotik olan doksorubisin (DOX), kanserli olmayan hücreleri de öldürerek toksisiteye neden olur. Cucumis melo var. agrestis Naudin (CM), Cucurbitaceae familyasına ait olan ve yüksek antioksidan içeriğe sahip bir bitkidir. Bu çalışmanın amacı, DOX kaynaklı kalp hasarına karşı farklı dozlarda uygulanan CM etkisini araştırmaktır.
Gereç ve Yöntem: 30 adet erkek rat, rastgele her grupta 6 hayvan olacak şekilde 5 gruba ayrıldı: 10 gün gavajla distile su verilen sıçanlara, deneyin 5. gününde intraperitoneal (i.p.) serum fizyolojik uygulaması yapılan kontrol grubu. Deneyin 5. Günü 15 mg/kg tek doz i.p. DOX uygulanan sıçanlardan oluşan DOX grubu. Deneyin 5. Günü 15 mg/kg tek doz i.p. DOX uygulanan sıçanlara 10 gün gavajla sırasıyla 100 mg/kg: (DOX+CM100), 250 mg/kg: (DOX+CM250), 500 mg/kg: (DOX+CM500) CM uygulanan gruplar. Son ilaç uygulamasından 24 saat sonra deney hayvanları anestezi altında sakrifiye edildi. Kalp dokusu histokimyasal ve immunohistokimyasal olarak incelendi.
Bulgular: Deney sonunda kalp dokusunun histopatolojik incelenmesinde; kontrol grubuyla karşılaştırıldığında DOX grubunda kas liflerinin dejenerasyonu, kas lifleri arasında vakuol benzeri yapılar, damarlarda konjesyon, kollateraller arasında ödem gibi bulgular görülmüştür. Bu bulgular tedavi grubu olan DOX+CM250 grubunda önemli derecede azalmıştır. DOX grubunda Caspase-3, HSP 70 ve NF-κB-p65 immunreaktivitelerinde bir artış görülürken (+++); DOX+CM250 grubunda ise bu bulgular önemli derecede azalmıştır (+).
Sonuç: DOX’un apoptotik süreci hızlandırdığı, enflamatuvar yanıtı tetikleyerek hücre içi stresi ve oksidatif stresi arttırdığı histokimyasal ve immunohistokimyasal olarak görülmüştür. 250 mg/kg dozunda uygulanan CM kardiyak yeniden yapılanmayı hızlandırmıştır.

Keywords

Doxorubicin, Cardiotoxicity, Cucumis melo var. agrestis Naudin, Caspase-3, HSP 70, NF-κB-p65

Ethical Statement

Ethical approval for the research project or animal experiments has been obtained with Decision Number 112, dated 08.11.2023, from the Local Ethics Committee for Animal Experiments at Afyon Kocatepe University under the reference number 49533702.

Effect of Cucumis melo var. agrestis Naudin on doxorubicin-induced cardiotoxicity in rats

Abstract

Purpose: Doxorubicin (DOX), a chemotherapeutic antibiotic, induces toxicity by also targeting non-cancerous cells. Cucumis melo var. agrestis Naudin (CM), a plant belonging to the Cucurbitaceae family with high antioxidant content, is examined in this study for its potential impact on DOX-induced cardiac damage at different doses.
Materials and Methods: 30 male rats were randomly divided into 5 groups, with 6 animals in each group: Control group, which received distilled water by gavage for 10 days, and intraperitoneal (i.p.) normal saline application on the 5th day of the experiment. The DOX group consisted of rats receiving a single i.p. dose of 15 mg/kg DOX on the 5th day of the experiment. Rats receiving a single intraperitoneal dose of 15 mg/kg DOX on the 5th day of the experiment were subjected to gavage for 10 days with doses of 100 mg/kg (DOX+CM100), 250 mg/kg (DOX+CM250), and 500 mg/kg (DOX+CM500) of CM, respectively. 24 hours after the last drug administration, the experimental animals were sacrificed under anesthesia. Heart tissue was examined histochemically and immunohistochemically.
Results: At the end of the experiment, histopathological examination of the heart tissue; Compared to the control group, histolopathological findings such as degeneration of muscle fibers, vacuole-like structures between muscle fibers, congestion in vessels, and edema between collaterals were observed in the DOX group. These findings significantly decreased in the DOX+CM250 treatment group. While an increase in Caspase-3, HSP 70 and NF-κB-p65 immunoreactivities was observed in the DOX group (+++); In the DOX+CM250 group, these findings decreased significantly (+).
Conclusion: DOX accelerated the apoptotic process, increased intracellular and oxidative stress, and triggered an inflammatory response, as demonstrated histochemically and immunohistochemically. CM administered at a dose of 250 mg/kg expedited cardiac remodeling.

Keywords

Doxorubicin, Cucumis melo var. agrestis Naudin, Caspase-3, HSP 70, NF-κB-p65

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