Therapeutic Effect of Sinapic Acid against 5-Fluorouracil-Induced Oxidative Stress and Inflammation in Rat Ovarium: An Experimental Approach

Year 2023, Volume: 2 Issue: 2, 1 - 7, 30.06.2023

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

https://doi.org/10.59518/farabimedj.1221397

Cited By: 4

Abstract

Tissue toxicity caused by 5-fluorouracil (5-FU) is associated with increased reactive oxygen species and inflammatory cytokines. Sinapic acid (SA) has both antioxidant and anti-inflammatory activities. Although SA has been shown to ameliorate chemical-induced tissue damage in various experimental models, its effects against 5-FU-induced ovarian damage have not yet been investigated. It was therefore aimed to evaluate the therapeutic potential of SA against 5-FU-induced ovarian damage in rats, together with the mechanisms of oxidative stress and inflammation for the first time in this study. Thirty rats were distributed into five groups: control, 5-FU (100 mg/kg) 5-FU+SA (2.5 and 5 mg/kg) and SA (5 mg/kg). 5-FU was applied to rats intraperitoneally on the 1st day of experiments and then SA was administrated for 3 successive days. Ovarian levels of lipid peroxidation [malondialdehyde (MDA)], oxidative stress (total oxidant status (TOS) and oxidative stress index (OSI)] antioxidant system [total antioxidant status (TAS), and catalase (CAT)], DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] and inflammatory [interleukin-6 (IL-6)] markers in ovarian tissues were determined using spectrophotometric methods. It was determined that a single dose of 5-FU administration in rats significantly increased oxidative stress and inflammation in the ovarian tissue and suppressed the antioxidant system compared to the control group (p<0.05). It was revealed that SA significantly suppressed ovarian inflammation by decreasing IL-6 levels, attenuates DNA damage by decreasing 8-OHdG levels, and also provides restoration of oxidative stress by decreasing MDA, TOS and OSI levels and increasing TAS and CAT levels in a dose-dependent manner. In conclusion, we found that SA exhibits therapeutic effects against 5-FU-induced ovarian damage. These findings suggest that SA may be a potentially useful agent for protection against chemotherapeutic-induced ovarian injury.

Keywords

5-fluorouracil, Inflammation, Ovarian damage, Oxidative stress, Rat, Sinapic acid

Sıçan Yumurtalık Dokusunda 5-Florourasil ile Uyarılan Oksidatif Stres ve İnflamasyona Karşı Sinapik Asitin Terapötik Etkisi: Deneysel Bir Yaklaşım

Abstract

5-florourasil (5-FU)'nun neden olduğu doku toksisitesi, artan reaktif oksijen türleri ve inflamatuar sitokinler ile ilişkilidir. Sinapik asit (SA) bir fenolik asittir ve hem antioksidan hem de anti-inflamatuar aktivitelere sahiptir. Çeşitli deneysel modellerde SA'nın kimyasal kaynaklı doku hasarını iyileştirdiği gösterilmiş olmasına rağmen, 5-FU kaynaklı yumurtalık hasarına karşı etkileri henüz araştırılmamıştır. Bu nedenle bu çalışmada SA'nın sıçanlarda 5-FU ile indüklenen yumurtalık hasarına karşı terapötik potansiyelinin oksidatif stres ve inflamasyon mekanizmaları ile birlikte ilk kez değerlendirilmesi amaçlandı. Otuz sıçan beş gruba ayrıldı: kontrol, 5-FU (100 mg/kg), 5-FU+SA (2,5 ve 5 mg/kg) ve SA (5 mg/kg). Sıçanlara deneylerin 1. günü intraperitoneal yoldan 5-FU, ardından 3 gün boyunca SA uygulandı. Yumurtalık lipid peroksidasyon seviyeleri [malondialdehit (MDA)], oksidatif stres (toplam oksidan durum (TOS) ve oksidatif stres indeksi (OSI)], antioksidan sistem [toplam antioksidan durum (TAS) ve katalaz (CAT)], DNA hasarı [8-hidroksi-2'-deoksiguanozin (8-OHdG)] ve inflamatuvar [interlökin-6 (IL-6)] belirteçlerinin düzeyleri spektrofotometrik yöntemlerle belirlendi. Sıçanlarda tek doz 5-FU uygulamasının kontrol grubuna göre yumurtalık dokusunda oksidatif stresi ve inflamasyonu anlamlı olarak arttırdığı ve antioksidan sistemi baskıladığı belirlendi (p<0.05). SA'nın IL-6 düzeylerini düşürerek over inflamasyonunu önemli ölçüde baskıladığı, 8-OHdG düzeylerini düşürerek DNA hasarını azalttığı ve ayrıca MDA, TOS ile OSI düzeylerini düşürerek ve TAS ile CAT düzeylerini artırarak oksidatif stresin restorasyonunu doza bağımlı bir şekilde sağladığı ortaya konuldu (p<0.05). Sonuç olarak, SA'nın 5-FU ile indüklenen yumurtalık hasarına karşı terapötik etkiler gösterdiğini bulduk. Bu bulgular SA'nın kemoterapötik kaynaklı yumurtalık hasarına karşı koruma için potansiyel olarak yararlı bir ajan olabileceğini düşündürmektedir.

Keywords

5-florourasil, İnflamasyon, Oksidatif stress, Rat, Sinapik asit, Yumurtalık hasarı

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