Gallik Asit Sıçanlarda Metotreksatın Neden Olduğu Oksidatif Yumurtalık Hasarını Azaltır

Year 2024, Volume: 3 Issue: 4, 119 - 125

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

https://doi.org/10.59518/farabimedj.1544287

Abstract

Metotreksat (MTX) kanser tedavisinde etkili bir kemoterapötik ajan olmasına rağmen, üreme sistemi de dahil olmak üzere sistemik doku toksisitesinin ortaya çıkması nedeniyle kullanımı sınırlanmaktadır. Gallik asit (GAL), son yıllarda oksidatif stres (OS) ile ilişkili çeşitli patolojik durumlara karşı faydalı etkiler gösterdiği kanıtlanmış bir fenolik bileşiktir. Bu çalışma, MTX'in neden olduğu yumurtalık hasarının tedavisinde GAL'ın terapötik potansiyelini ilk kez araştırmak için tasarlandı. Yetişkin dişi sıçanlar (n=30) rastgele beş gruba ayrıldı: kontrol, MTX, MTX+GAL (2,5 ve 5 mg/kg) ve yalnızca yüksek doz GAL (5 mg/kg). Yumurtalık toksisitesi tek doz intraperitoneal MTX (20 mg/kg) enjeksiyonu ile oluşturuldu. Tedavi gruplarına ise 2,5 ve 5 mg/kg dozundaki GAL ardışık üç gün boyunca intraperitoneal yoldan uygulandı. Çalışmanın beşinci gününde toplanan yumurtalık doku örneklerinde OS, inflamasyon ve apoptoz seviyeleri spektrofotometrik yöntemler kullanılarak belirlendi. Bulgular, GAL tedavisinin, MTX'e maruz bırakılan sıçanlarda yumurtalık lipid peroksidasyon, inflamasyon ve apoptoz seviyesini azalttığını ve yumurtalık antioksidan sistemini desteklediğini gösterdi. Bu çalışmanın sonuçları, GAL'ın MTX ile ilişkili oksidatif ve inflamatuar yumurtalık hasarını iyileştirme potansiyeline sahip olabileceğini göstermektedir. GAL'ın bu yumurtalık koruyucu etkisinin daha kapsamlı klinik öncesi çalışmalarla doğrulanması gerekmektedir.

Keywords

Apoptoz, Gallik asit, İnflamasyon, Metotreksat, Oksidatif stress, Rat modeli, Yumurtalık hasarı

Gallic Acid Alleviates Methotrexate‐Induced Oxidative Ovarian Damage in Rats

Abstract

Although methotrexate (MTX) is an effective chemotherapeutic agent in the treatment of cancer, its use is limited due to the occurrence of systemic tissue toxicity, including those affecting the reproductive system. Gallic acid (GAL) is a phenolic compound that has been demonstrated to exert beneficial effects in a number of pathological conditions associated with oxidative stress (OS) in recent years. This study was designed to investigate the potential therapeutic benefits of GAL in the treatment of MTX-induced ovarian damage, for the first time. Adult female rats (n=30) were randomly allocated to five groups: control, MTX, MTX+GAL (2.5 and 5 mg/kg) and high-dose GAL only (5 mg/kg). A single intraperitoneal injection of MTX (20 mg/kg) was administered to induce ovarian toxicity. The treatment groups were administered 2.5 and 5 mg/kg of GAL intraperitoneally for a period of three consecutive days. The levels of OS, inflammation and apoptosis were determined in ovarian tissue samples collected on the fifth day of the study using spectrophotometric methods. The results showed that GAL treatment reduced the level of ovarian lipid peroxidation, inflammation, and apoptosis and promoted the ovarian antioxidant system in rats subjected to MTX. The results of this study indicate that GAL may have the potential to ameliorate MTX-associated oxidative and inflammatory ovarian damage. The ovarian protective effect of GAL requires further confirmation through more extensive preclinical studies.

Keywords

Apoptosis, Gallic acid, Inflammation, Methotrexate, Ovarian damage, Oxidative stress, Rat model

Ethical Statement

This study was approved by the Local Animal Research Ethics Committee of Karadeniz Technical University (Protocol no: 2023/07) 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.

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