The Therapeutic Effect of p-Coumaric Acid on Lung Toxicity Induced by Methotrexate in Rats

Year 2024, , 57 - 62, 30.06.2024

Selim Demir , Nihal Türkmen Alemdar , Elif Ayazoglu Demir , Ahmet Mentese , Yüksel Aliyazıcıoğlu

https://doi.org/10.59518/farabimedj.1484155

Abstract

The use of methotrexate (MTX), a chemotherapy agent, is limited by a number of side effects, including pulmonary toxicity. Oxidative stress (OS) and inflammation are possible mechanisms of MTX-associated pulmonary toxicity. p-Coumaric acid (PCA) is a phenolic acid that has been demonstrated to exert a number of beneficial effects on human health, particularly in relation to antioxidant and anti-inflammatory activity. The potential effects of PCA in reducing MTX-induced pulmonary toxicity were investigated in the current study. After MTX (20 mg/kg) was administered to the rats on day 1, two different doses of PCA (2 and 4 mg/kg) were administered intraperitoneally for 3 days and the levels of OS, inflammation and apoptosis were assessed in the lung tissues collected on day 5. PCA applications largely eliminated MTX-induced OS, inflammation and apoptosis in lung tissue via enhancing the capacity of endogenous antioxidant system. The therapeutic effect of PCA against MTX-induced pulmonary toxicity should be re-evaluated in more systematic studies.

Keywords

Apoptosis, Inflammation, Methotrexate, Oxidative stress, p-Coumaric acid, Pulmonary toxicity

Ethical Statement

This study was approved by the Local Animal Research Ethics Committee of Karadeniz Technical University (Protocol no: 2023/06) and performed according to the animal research reporting of in vivo experiments (ARRIVE) guidelines.

Thanks

The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice and Research Center of Karadeniz Technical University for professional assistance with the experimental studies.

Sıçanlarda Metotreksatın Neden Olduğu Akciğer Toksisitesi Üzerine p-Kumarik Asidin Terapötik Etkisi

Abstract

Bir kemoterapötik ajan olarak metotreksatın (MTX) kullanımı, akciğer toksisitesi de dahil olmak üzere bir takım yan etkiler nedeniyle sınırlıdır. Oksidatif stres (OS) ve inflamasyon, MTX ile ilişkili akciğer toksisitesinin olası mekanizmalarıdır. p-Kumarik asit (PCA), özellikle antioksidan ve anti-inflamatuar olmak üzere insan sağlığı üzerinde çeşitli yararlı etkileri olan bir fenolik asittir. Bu çalışmada PCA'nın MTX kaynaklı akciğer toksisitesini azaltmadaki potansiyel etkileri araştırıldı. Ratlara 1. günde MTX (20 mg/kg) enjeksiyonunu takiben 3 gün boyunca iki farklı dozda PCA (2 ve 4 mg/kg) intraperitoneal olarak uygulandıktan sonra 5.günde akciğer dokuları toplanarak OS, inflamasyon ve apoptoz düzeyleri değerlendirildi. PCA uygulamaları, endojen antioksidan sistemin kapasitesini artırarak akciğer dokusunda MTX'in neden olduğu OS, inflamasyon ve apoptozu büyük ölçüde ortadan kaldırdı. PCA'nın MTX kaynaklı akciğer toksisitesine karşı terapötik etkisinin daha sistematik çalışmalarla yeniden değerlendirilmesi gerekmektedir.

Keywords

Akciğer toksisitesi, Apoptoz, İnflamasyon, Metotreksat, Oksidatif stres, p-Kumarik

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