Beta-karyofilenin sıçanlarda tiyoasetamid kaynaklı kalp hasarına karşı kardiyoprotektif etkisi

Öz

Tiyoasetamid (TAA), deneysel toksikolojide karaciğer hastalıklarını modellemek için yaygın olarak kullanılmaktadır. Ancak son bulgular, TAA kaynaklı karaciğer hasarının miyokardda yapısal ve işlevsel değişikliklere yol açabileceğini göstermektedir. Bu çalışmada, sıçanlarda TAA maruziyetinin neden olduğu kalp hasarına karşı beta-karyofilenin (BCP) kardiyoprotektif etkileri değerlendirilmiştir. Araştırmamızda, 60 Sprague Dawley erkek sıçan, her grupta 10 hayvan olacak şekilde 6 gruba ayrılmıştır. Deneyin ilk üç günü sıçanlara TAA (200 mg/kg) intraperitoneal olarak, BCP (100-200 mg/kg) ise 14 gün boyunca oral olarak uygulanmıştır. Deneyden sonra kalp dokuları toplandı ve malondialdehit (MDA), süperoksit dismutaz (SOD) ve katalaz (CAT) düzeyleri manuel biyokimyasal yöntemlerle, PKR benzeri ER kinaz (PERK), aktive edici transkripsiyon faktörü (ATF-4), nükleer faktör kappa B (NF-κB) ve tümör nekroz faktörü-alfa (TNF-α) mRNA transkripsiyon düzeyleri ise RT-PCR kullanılarak analiz edildi. Ayrıca kalp örnekleri histopatolojik olarak incelendi. Bulgularımız TAA maruziyetinin kalp dokusunda MDA düzeylerini artırdığını ve SOD ve CAT aktivitelerini önemli ölçüde azalttığını gösterdi. Ayrıca inflamasyon belirteçlerinin (NF-κB ve TNF-α) ve ER stres biyobelirteçlerinin (PERK ve ATF-4) ekpresyon düzeylerinde önemli bir artışa yol açtı. BCP uygulaması, PERK ve ATF-4 ifadesini baskılayarak ER stresini hafifletti. Ayrıca, histopatolojik gözlemler BCP tedavisinin TAA kaynaklı kardiyak doku hasarını iyileştirdiğini gösterdi. BCP tedavisi, oksidatif hasarın neden olduğu ER stresini hafifletmiş ve inflamatuar belirteçlerin seviyelerini düşürmüştür. Sonuç olarak, BCP tedavisinin TAA kaynaklı oksidatif stresi, ER stresini ve inflamasyonu azaltarak kardiyotoksisiteye karşı koruma sağlayabileceği belirlenmiştir.

Anahtar Kelimeler

• beta-karyofilen
• kardiyotoksisite
• oksidatif stres
• rat
• tiyoasetamid

Cardioprotective effect of Beta-caryophyllene on thioacetamide-induced heart damage in rats

Öz

Thioacetamide (TAA) is widely used in experimental toxicology to model liver diseases. However, recent findings indicate that TAA-induced liver injury can lead to structural and functional changes in the myocardium. This study evaluated the cardioprotective effects of beta-caryophyllene (BCP) against cardiac damage caused by TAA exposure in rats. In our research, 60 Sprague Dawley male rats were divided into 6 groups with 10 animals in each group. TAA (200 mg/kg) was administered intraperitoneally to rats for the first three days of the experiment, and BCP (100-200 mg/kg) was administered orally for 14 days. After the experiment, heart tissues were collected, and malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed using manual biochemical methods, and PKR-like ER kinase (PERK), activating transcription factor (ATF-4), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α) mRNA transcription levels were analyzed using RT-PCR. Furthermore, heart samples were examined histopathologically. Our findings showed that TAA exposure increased MDA levels in heart tissue and significantly decreased SOD and CAT activities. It also led to a significant increase in the expression levels of inflammatory markers (NF-κB and TNF-α) and ER stress biomarkers (PERK and ATF-4). BCP administration alleviated ER stress by suppressing PERK and ATF-4 expression. Furthermore, histopathological observations indicated that BCP treatment ameliorated TAA-induced cardiac tissue damage. BCP therapy relieved ER stress generated by oxidative damage and reduced the levels of inflammatory markers. Consequently, it was determined that BCP treatment may protect against cardiotoxicity by reducing TAA-induced oxidative stress, ER stress, and inflammation.

Anahtar Kelimeler

• beta-caryophyllene
• cardiotoxicity
• oxidative stress
• rat
• thioacetamide

Kaynakça

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