Ratlarda diklofenak ile indüklenen kardiyotoksisite üzerine krisinin etkilerinin oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ile değerlendirilmesi

Öz

Diklofenak (DF), steroid olmayan anti-inflamatuar ilaçlar arasındadır ve yüksek dozlarda kalp dahil çeşitli dokularda toksik etkiler göstermektedir. Krisin (KRS) antioksidan ve anti-apoptotik gibi birçok yararlı etkiye sahiptir. Sunulan çalışmada DF ile indüklenen kardiyotoksisite üzerine KRS’nin etkileri araştırılmıştır. Bu amaçla Sprague Dawley ratlara DF ve/veya KRS uygulamaları yapıldıktan sonra kalp dokularında oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ve serum CK-MB seviyeleri analiz edildi. Elde edilen veriler DF ile indüklenen oksidatif stresin KRS uygulamasından sonra SOD, CAT ve GPx enzimlerinin ekspresyonlarının tetiklenmesi ve GSH seviyelerinin artması ile hafiflediğini ve MDA seviyelerinde azalma meydana geldiğini göstermektedir. Ayrıca ER stres belirteçleri olan ve DF’nin indüklediği ATF-6, PERK, IRE1 ve GRP78 ekspresyonlarının KRS tedavisinden sonra aşağı yönlü düzenlendiği belirlendi. ER stresi ile bağlantılı olarak KRS’nin Bax ve Kaspaz-3 ekspresyonlarını baskıladığı ve Bcl-2 ekspresyonunu arttırdığı da elde edilen veriler arasındadır. Ayrıca kalp hasarının önemli bir göstergesi olan CK-MB seviyelerinin KRS uygulamasından sonra azaldığı görüldü. Sonuç olarak DF’nin neden olduğu kardiyotoksisiteye karşı KRS’nin önemli bir koruma sağladığı tespit edildi.

Anahtar Kelimeler

• Diklofenak
• endoplazmik retikulum stresi
• kardiyotoksisite
• krisin
• oksidatif stres

Evaluation of the Effects of Chrysin on Diclofenac-Induced Cardiotoxicity in Rats by the Markers of Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis

Öz

Diclofenac (DF) is among non-steroidal anti-inflammatory drugs and in high doses it has toxic effects on various tissues, including the heart. Chrysin (CRS) has many beneficial effects such as antioxidant and anti-apoptotic. In the present study, the effects of CRS on DF-induced cardiotoxicity were investigated. For this purpose, after DF and/or CRS treatments were applied to Sprague Dawley rats, the markers of oxidative stress, endoplasmic reticulum stress and apoptosis in heart tissues and serum CK-MB levels were analyzed. The data obtained displayed that oxidative stress induced by DF was alleviated by triggering the expression of SOD, CAT and GPx enzymes and increasing GSH levels after CRS administration, and a decrease in MDA levels occurred. It was also determined that the expressions of ATF-6, PERK, IRE1 and GRP78, which are ER stress markers and induced by DF, were downregulated after CRS treatment. Additionally, CRS suppressed Bax and Caspase-3 expressions and increased Bcl-2 expression in connection with ER stress. Another finding of this study demonstrated that CK-MB levels, which are an important indicator of heart damage, decreased after CRS administration. As a result, CRS provided a significant protection against cardiotoxicity caused by DF.

Anahtar Kelimeler

• Cardiotoxicity
• chrysin
• diclofenac
• endoplasmic reticulum stress
• oxidative stress

Kaynakça

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