Ayşegül Burçin YILDIRIM, Emin KAYMAK, Tayfun CEYLAN, Ali AKIN, Nurhan KULOĞLU, Meryem SAYAN, Necla DEĞER, Esra ÖNAL, Derya KARABULUT

Timokinon metotreksatın neden olduğu kalp hasarını azaltır: sıçanlarda histopatolojik bir çalışma

Amaç: Bu çalışmada, sıçanlarda MTX ile indüklenen kardiyak toksisitede timokinonun kardiyak doku üzerindeki etkisinin çeşitli parametrelerle değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Grup I'e (n=8) 10 gün boyunca intraperitoneal salin uygulandı. Grup II'ye (n=8) 10 gün boyunca intraperitoneal zeytinyağı uygulandı. Grup III (n=8) 10 gün boyunca 10 mg/kg timokinon (THQ) intraperitoneal olarak almıştır. Grup IV'e (n=8) deneyin 1. gününde tek doz 20 mg/kg Metotreksat (MTX), 500 mg/20 ml, intraperitoneal olarak uygulandı. Metotreksat sıvı formda olduğu için herhangi bir çözücü kullanılmamıştır. Grup V (n=8) MTX: 1. gün 20 mg/kg tek doz intraperitoneal; THQ: 10mg/kg i.p. 10 gün boyunca uygulandı. Deney süresinin sonunda sıçanlar kalp dokusu analizi için sakrifiye edilmiştir. Kalp dokusunun yapısı hematoksilen-eozin boyama ile değerlendirildi. İmmünohistokimyasal olarak, konneksin-43, HSP90 ve HIF-1α antikorları ile boyandı. Bulgular: Grup IV’ün histopatolojisinde bozulmalar olduğu belirlendi, THQ’nun bu bozulmayı iyileştirdiği görüldü. Bunun yanı sıra, diğer gruplara göre; konneksin-43 immunureaktivitesi, Grup IV’de: 108.5±7.4 ile en düşük, HSP90 immunureaktivitesi diğer gruplara göre, Grup IV’de: 103.6±10.4 en yüksek, HIF-1α immunureaktivitesi diğer gruplara göre Grup IV’de: 95.2 ±9.1 en yüksek değerlerdeydi. Sonuç: Timokinon, MTX toksisitesine karşı interkalar disklerde iletimi sağlayan proteinlerden biri olan konneksin-43, hücre içindeki şaperonlardan biri olan HSP90 ve HIF-1α ekspresyonu üzerine olumlu etki göstermektedir. Aynı zamanda THQ, kalp dokusunda histopatolojik olarak kardiyoprotektif etki göstererek anlamlı bir iyileşme sağlamaktadır.

Anahtar Kelimeler:

Konneksin-43, HSP90, HIF-1α, metotreksat, timokinon

Thymoquinone reduces methotrexate-induced heart damage: a histopathological study in rats

Purpose: The study aimed to evaluate the effect of thymoquinone on cardiac tissue in MTX-induced cardiac toxicity in rats with various parameters. Materials and Methods: Group I (n:8) was administered intraperitoneal saline for 10 days. Intraperitoneal olive oil was applied to Group II (n:8) for 10 days. Group III (n:8) was administered a single dose of 20 mg/kg Methotrexate (MTX) (500 mg/20 ml) intraperitoneally on the 1st day of the experiment. Since Methotrexate was in liquid form, no solvent was used. Group IV (n:8) received 10 mg/kg Thymoquinone (THQ) intraperitoneally for 10 days. Group V (n:8) (MTX: (20 mg/kg single dose intraperitoneally on the 1st day); THQ: 10mg/kg i.p. administered for 10 days. At the end of the experimental period, the rats were sacrificed for analysis of heart tissue. The structure of heart tissue was evaluated by haematoxylin-eosin staining. Immunohistochemically, connexin-43, HSP90, and HIF-1α antibodies were stained. The results were analysed statistically. Results: According to our results, thymoquinone has a positive effect on the expression of Cx43, one of the proteins providing transmission in the intercalary discs, HSP90, one of the chaperones in the cell, and HIF-1α expression against MTX toxicity and provides a significant improvement by showing a cardioprotective effect histopathologically. Conclusion: THQ could be considered a crucial cardioprotective phytochemical against MTX cardiotoxicity.

Keywords:

Key words: Conneksin-43, HIF-1α, HSP90, Methotrexate, Thymoquinone,

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