Evaluation of Therapeutic Effect of Chrysin Against 5-Fluorouracil-Induced Ovarian Damage in Rats

Year 2023, Volume: 2 Issue: 1, 1 - 7, 30.03.2023

Elif Ayazoglu Demir , Ahmet Mentese , Selim Demir , Hatice Küçük , Nihal Türkmen , Yüksel Aliyazıcıoğlu

Abstract

5-fluorouracil (5-FU) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Many studies have confirmed that oxidative stress and inflammation play a major role in the pathogenesis of 5-FU-induced damage in the various tissues. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. The aim of this study was to determine the therapeutic effect of CHS against 5-FU-induced oxidative stress and inflammation in the ovary tissue of rats for the first time. Thirty female rats were divided into 5 groups: control, 5-FU (100 mg/kg), 5-FU+CHS (1 mg/kg), 5-FU+CHS (2 mg/kg) and CHS (2 mg/kg). 5-FU treatment was administered intraperitoneally (i.p.) on the first day and CHS (i.p.) were applied for the following 3 days. The ovarian tissue levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), catalase (CAT) and interleukin-6 (IL-6) were determined using spectrophotometric methods. MDA, TOS, 8-OHdG and IL-6 levels were significantly higher (p<0.05) and TAS and CAT levels level were significantly lower (p<0.05) in the 5-FU group than in the control group. CHS treatments significantly restored the levels of oxidative stress and inflammation parameters in a dose-dependent manner (p<0.05). Our results suggest that CHS can have a therapeutic effect against 5-FU-induced ovarian damage and therefore the use of CHS after chemotherapy may be beneficial in abolishing 5-FU-induced reproductive toxicity.

Keywords

5-fluorouracil, Chrysin, Inflammation, Ovarian damage, Oxidative stress

Sıçanlarda 5-Florourasil Kaynaklı Yumurtalık Hasarına Karşı Krisinin Terapötik Etkisinin Değerlendirilmesi

Abstract

5-florourasil (5-FU), çeşitli maligniteleri tedavi etmek için etkili ve yaygın olarak kullanılan bir kemoterapötik ajandır, ancak doza bağlı doku toksisitesi nedeniyle terapötik kullanımı sınırlıdır. Birçok çalışma, çeşitli dokularda 5-FU'nun neden olduğu hasarın patogenezinde oksidatif stres ve inflamasyonun önemli bir rol oynadığını doğrulamıştır. Doğal bir flavon olan krisin (CHS), antioksidan, anti-inflamatuvar ve antikanser de dahil olmak üzere çeşitli faydalı aktiviteler sergileyebilmektedir. Bu çalışmanın amacı, sıçanların yumurtalık dokusunda 5-FU ile indüklenen oksidatif stres ve inflamasyona karşı CHS'nin terapötik etkisini ilk kez belirlemekti. Otuz adet dişi sıçan kontrol, 5-FU (100 mg/kg), 5-FU+CHS (1 mg/kg), 5-FU+CHS (2 mg/kg) ve CHS (2 mg/kg) olmak üzere 5 gruba ayrıldı. İlk gün intraperitoneal (i.p.) 5-FU tedavisi, takip eden 3 gün CHS (i.p.) uygulandı. Yumurtalık dokularında malondialdehit (MDA), toplam oksidan durum (TOS), toplam antioksidan durum (TAS), 8-hidroksi-2'-deoksiguanozin (8-OHdG), katalaz (CAT) ve interlökin-6 (IL-6) seviyeleri spektrofotometrik yöntemlerle belirlendi. 5-FU grubunda kontrol grubuna göre MDA, TOS, 8-OHdG ve IL-6 düzeyleri anlamlı olarak yüksek iken (p<0,05), TAS ve CAT düzeyleri ise istatistiksel olarak anlamlı düzeyde düşüktü (p<0,05). CHS tedavileri, oksidatif stres ve inflamasyon parametrelerinin seviyelerini doza bağlı bir şekilde istatistiksel olarak anlamlı derecede düzeltti (p<0,05). Sonuçlarımız, CHS'nin 5-FU ile indüklenen yumurtalık hasarına karşı terapötik bir etkiye sahip olabileceğini ve bu nedenle kemoterapiden sonra CHS kullanımının 5-FU ile indüklenen üreme toksisitesini ortadan kaldırmada faydalı olabileceğini düşündürmektedir.

Keywords

5-florourasil, İnflamasyon, Krisin, Oksidatif stress, Rat, Yumurtalık dokusu hasarı, 5-fluorouracil, Chrysin, Inflammation, Ovarian damage, Oxidative stress

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