ATORVASTİN VE ROSUVASTATİNİN NEDEN OLDUĞU MİYOPATİYE KARŞI KAFEİK ASİD FENETİL ESTERİN KORUYUCU ETKİSİ

AMAÇ: Statinlerin bazı hastalarda myopatiye yol açması nedeni ile hastanın tedaviye uyumu azalmakta, ilacın kullanılmasına son verilmekte veya kullanılan ilaç değiştirilmektedir. Bu çalışmada statinlerin myopatiye neden olabileceği iki durum olarak oksidatif stress ve inflamasyon üzerinde çalışılmış ve Kafeik asit fenil ester (CAPE)’in koruyucu rolü deneysel olarak test edilmiştir. GEREÇ VE YÖNTEM: Çalışmada rabdomiyosarkom (RD) hücre hatları kullanılmıştır. Hücreler kontrol, atorvastatin, rosuvastatin, CAPE, atorvastatin+CAPE ve rosuvastatin+CAPE olmak üzere 6 gruba ayrılmıştır. Spektrofotometrik olarak Total Antioksidan Kapasite (TAC), Total Oksidan Kapasite (TOC) ve Oksidatif Stres İndeksi (OSI) analizleri yapılmış; İnterlökin 6 (IL-6) düzeyleri hem protein düzeyinde hem de real time PCR ile mRNA ekpresyonu düzeyinde gösterilmiştir. BULGULAR: Kontrol grubunda 1739 olan OSI atorvastatin uygulaması ile 3814’e çıkmış, atorvastatinin CAPE ile kombinasyonu sonucunda ise 2109’a inmiştir. Rosuvastatin ve Rosuvastatinin CAPE ile kombinasyonu sonucunda kontrol grubuna göre OSI bakımından bir değişiklik olmamıştır. Atorvastin grubunda IL-6 mRNA ekspresyon düzeyleri kontrol grubuna benzer bulunurken, Rosuvastatin grubunda kontrol grubuna nazaran 2,369 kat artış gözlenmiştir. Rosuvastatinin CAPE ile kombinasyonu neticesinde IL-6 mRNA ekspresyon düzeylerinin kontrol grubu seviyesine çekildiği tespit edilmiştir. SONUÇ: Bu çalışmada Atorvastatinin RD hücre hatlarında oksidatif stresi tetiklediği, rosuvastatinin ise IL -6 mRNA ekspresyon düzeyini artırarak proinflamasyona giden sürecin önünü açtığı gözlemlenmiştir. Atorvastatinin neden olduğu oksitadif stresin ve rosuvastatinin neden olduğu inflamasyonun baskılanmasında CAPE kombinasyonunun işlevsel olduğu tespit edilmiştir. Bu bakımdan tedavide atorvastatin ve rosuvastatinin CAPE ile kombinasyonunun statinlerin neden olduğu kas hasarı üzerine hasta yararına olumlu sonuçlarının olabileceği gösterilmiştir.

Anahtar Kelimeler:

Atorvastatin, Rosuvastatin Kalsiyum, Miyopati, Kafeik Asid Fenetil Ester

PROTECTIVE EFFECT OF CAFFEIC ACID PHENETHYL ESTER AGAINST MYOPATHY INDUCED BY ATORVASTIN AND ROSUVASTATIN

OBJECTIVE: Due to the fact that statins cause myopathy in some patients, the patient's compliance with the treatment decreases, and the treatment is interrupted or drug is changed. In this study, oxidative stress and inflammation, two conditions in which statins can cause myopathy, were studied and the protective role of Caffeic acid phenethyl ester (CAPE) was tested experimentally. MATERIAL AND METHODS: Rhabdomyosarcoma (RD) cell lines were used in the study. Cells were divided into 6 groups as control, atorvastatin, rosuvastatin, CAPE, atorvastatin+CAPE and rosuvastatin+CAPE. Total Antioxidant Capacity (TAC), Total Oxidative Capacity (TOC), and Oxidative Stress Index (OSI) analyzes were made spectrophotometrically; Interleukin 6 (IL-6) levels were demonstrated both at the protein level by ELISA and at the level of mRNA expression by real time PCR. RESULTS: OSI, which was 1739 in the control group, increased to 3814 with atorvastatin application and decreased to 2109 with the combination of atorvastatin and CAPE. There was no change in OSI levels in Rosuvastatin and Rosuvastatin and CAPE combination compared to the control group. While IL-6 mRNA expression levels were found to be similar to the control group in the atorvastin group, an increase of 2.369 times was observed in the Rosuvastatin group compared to the control group. As a result of the combination of rosuvastatin with CAPE, it was determined that IL-6 mRNA expression levels were reduced to the level of the control group. CONCLUSIONS: In this study, it was observed that atorvastatin triggered oxidative stress in RD cell lines, while rosuvastatin increased the expression level of IL-6 mRNA and paved the way for the process leading to proinflammation. The combination of CAPE was found to be functional in suppressing oxidative stress caused by atorvastatin and inflammation caused by rosuvastatin. In this regard, it has been shown that the combination of atorvastatin and rosuvastatin with CAPE may have positive results for the benefit of the patient on muscle damage caused by statins.

Keywords:

Atorvastatin, Rosuvastatin Calcium, Myopathy, Caffeic Acid Phenethyl Ester,

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