Journals / Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi / 2026 / Cilt: 6 Sayı: 1

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

Beta-karyofilenin sıçanlarda tiyoasetamid kaynaklı kalp hasarına karşı kardiyoprotektif etkisi

Esra Aktas Senocak(ATATURK UNIVERSITY, HORASAN VOCATIONAL SCHOOL)0000-0003-1685-0803
Tuba Karaarslan(ATATÜRK ÜNİVERSİTESİ, VETERİNER FAKÜLTESİ)0000-0003-4039-3497
İsmail Bolat(ATATÜRK ÜNİVERSİTESİ, VETERİNER FAKÜLTESİ)0000-0003-1398-7046
Pages
15–23
Publication Date
2026-01-12
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

However, recent findings indicate that TAA-induced liver injury can lead to structural and functional changes in the myocardium.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Thioacetamide (TAA) is widely used in experimental toxicology to model liver diseases.
📊
Key Findings & Data:In our research, 60 Sprague Dawley male rats were divided into 6 groups with 10 animals in each group.
💡
Conclusion & Impact:However, recent findings indicate that TAA-induced liver injury can lead to structural and functional changes in the myocardium.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:beta-karyofilen · kardiyotoksisite · oksidatif stres

Abstract

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.

Özet

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.

🔖

Cite This Article

Senocak, E. A., Karaarslan, T., Bolat, İ. (2026). Cardioprotective effect of Beta-caryophyllene on thioacetamide-induced heart damage in rats. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi, Cilt: 6 Sayı: 1, 15–23. https://doi.org/10.62425/jlasp.1771098

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (25)

  1. Aebi, H. (1984). Catalase in vitro methods. In Methods in Enzymology (Vol. 105, pp. 121–126). Academic Press. https://doi.org/10.1016/S0076-6879(84)05016-3
  2. Almohawes, Z. N., Okail, H. A., Al-Megrin, W. A., ElKhadragy, M. F., Ibrahim, M. A., Fathalla, A. S., Soliman, D., & Mohamed, S. R. (2025). The cardioprotective effect of whey protein against thioacetamide-induced toxicity through its antioxidant, anti-inflammatory, and antiapoptotic effects in male albino rats. Frontiers in Veterinary Science, 12, 1590722. https://doi.org/10.3389/fvets.2025.1590722
  3. Al-Taee, H., Azimullah, S., Meeran, M. F. N., Alaraj Almheiri, M. K., Al Jasmi, R. A., Tariq, S., Khan, M. A. B., Adeghate, E., & Ojha, S. (2019). β-caryophyllene, a dietary phytocannabinoid attenuates oxidative stress, inflammation, apoptosis and prevents structural alterations of the myocardium against doxorubicininduced acute cardiotoxicity in rats: An in vitro and in vivo study. European Journal of Pharmacology, 858, 172467. https://doi.org/10.1016/j.ejphar.2019.172467
  4. Amirtharaj, G. J., Natarajan, S. K., Pulimood, A., Balasubramanian, K. A., Venkatraman, A., & Ramachandran, A. (2017). Role of oxygen free radicals, nitric oxide and mitochondria in mediating cardiac alterations during liver cirrhosis induced by thioacetamide. Cardiovascular Toxicology, 17(2), 175– 184. https://doi.org/10.1007/s12012-016-9371-1
  5. Apaydin Yildirim, B., Dogan, T., Aktas Senocak, E., Yildirim, S., Kordali, S., & Yildirim, F. (2025). Punica granatum L. peel extract protects diabetic nephropathy by activating the Nrf-2/HO-1 pathway. Acta Diabetologica, 62(4), 469–480. https://doi.org/10.1007/s00592-024-02371-5
  6. Bolat, M., Çelebi, F., Şengül, E., Çınar, İ., Yıldırım, S., & Bolat, İ. (2025). Investigation of the protective effect of betacaryophyllene against indomethacin-induced gastric ulcer in rats: In vivo and in vitro study. NaunynSchmiedeberg’s Archives of Pharmacology, 1–19. https://doi.org/10.1007/s00210-025-04269-7
  7. Bolat, M., Yilmaz, T. E., Çeğindir, M., Atasever, A., Doğan, T., Yildirim, S., Sağlam, Y. S., Çomakli, S., & Bolat, İ. (2025). Syringic acid alleviates cadmium-induced neurotoxicity in rats by modulating cellular signaling pathways. International Immunopharmacology, 158, 114816. https://doi.org/10.1016/j.intimp.2025.114816
  8. Eisvand, F., Imenshahidi, M., Ghasemzadeh Rahbardar, M., Tabatabaei Yazdi, S. A., Rameshrad, M., Razavi, B. M., & Hosseinzadeh, H. (2022). Cardioprotective effects of alpha-mangostin on doxorubicin-induced cardiotoxicity in rats. Phytotherapy Research, 36(1), 506–524. https://doi.org/10.1002/ptr.7356
  9. El-Gendy, H. F., Khalifa, H. K., Omran, A., Korany, R. M. S., Selim, S., Hussein, E., Alhotan, R. A., Ayyoub, A., & Masoud, S. R. (2024). Unveiling the potential of silymarin, Spirulina platensis, and Chlorella vulgaris towards cardiotoxicity via modulating antioxidant activity, inflammation, and apoptosis in rats. Life, 14(10), 1289. https://doi.org/10.3390/life14101289
  10. Ezhilarasan, D. (2023). Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models. Environmental Toxicology and Pharmacology, 99, 104093. https://doi.org/10.1016/j.etap.2023.104093
  11. Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., & Sinicropi, M. S. (2019). β-caryophyllene: A sesquiterpene with countless biological properties. Applied Sciences, 9(24), 5420. https://doi.org/10.3390/app9245420
  12. Gushiken, L. F. S., Beserra, F. P., Hussni, M. F., Gonzaga, M. T., Ribeiro, V. P., De Souza, P. F., Campos, J. C. L., Massaro, T. N. C., Hussni, C. A., Takahira, R. K., Marcato, P. D., Bastos, J. K., & Pellizzon, C. H. (2022). Betacaryophyllene as an antioxidant, anti-inflammatory and re-epithelialization agent in a rat skin wound excision model. Oxidative Medicine and Cellular Longevity, 2022, 9004014. https://doi.org/10.1155/2022/9004014
  13. Hassan, N. F., El-Ansary, M. R., El-Ansary, A. R., El-Saied, M. A., & Zaki, O. S. (2024). Unveiling the protective potential of mirabegron against thioacetamide-induced hepatic encephalopathy in rats: Insights into cAMP/PPAR-γ/pERK1/2/p-S536 NF-κB p65 and p-CREB/BDNF/TrkB in parallel with oxidative and apoptotic trajectories. Biochemical Pharmacology, 229, 116504. https://doi.org/10.1016/j.bcp.2024.116504
  14. Jin, X., Li, Y., Li, J., Cheng, L., Yao, Y., Shen, H., Wang, B., Ren, J., Ying, H., & Xu, J. (2022). Acute bone damage through liver-bone axis induced by thioacetamide in rats. BMC Pharmacology and Toxicology, 23(1), 1–10. https://doi.org/10.1186/s40360-022-00568-4
  15. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402–408. https://doi.org/10.1006/meth.2001.1262
  16. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193(1), 265– 275.
  17. Mansoori, R., Ashrafpour, M., Asghari, M. H., Golchoobian, R., Hosseini, S. M., Reiter, R. J., Karim, B., Moghadamnia, A. A., & Kazemi, S. (2025). Protective effects of melatonin against 5-fluorouracil-induced cardiotoxicity in rats: A comprehensive evaluation of oxidative, inflammatory, and apoptotic pathways. Toxicology and Applied Pharmacology, 499, 117343. https://doi.org/10.1016/j.taap.2025.117343
  18. Megahed, A., Gadalla, H., Abdelhamid, F. M., Almehmadi, S. J., Khan, A. A., Albukhari, T. A., & Risha, E. F. (2023). Vitamin D ameliorates the hepatic oxidative damage and fibrotic effect caused by thioacetamide in rats. Biomedicines, 11(2), 424. https://doi.org/10.3390/biomedicines11020424
  19. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical Biochemistry, 16(2), 359–364. https://doi.org/10.1016/0003-2697(66)90167-9
  20. Refaat, B., & El-Boshy, M. (2022). Protective antioxidative and anti-inflammatory actions of β-caryophyllene against sulfasalazine-induced nephrotoxicity in rat. Experimental Biology and Medicine, 247(8), 691–699. https://doi.org/10.1177/15353702211073804
  21. Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34(3), 497–500. https://doi.org/10.1093/clinchem/34.3.497
  22. Türkmen, N. B., Yüce, H., Taşlidere, A., Şahin, Y., & Çiftçi, O. (2022). The ameliorative effects of nerolidol on thioacetamide-induced oxidative damage in heart and kidney tissue. Turkish Journal of Pharmaceutical Sciences, 19(1), 1. https://doi.org/10.4274/tjps.galenos.2021.30806
  23. Xia, J., Hu, J., Zhang, R., Liu, W., Zhang, H., Wang, Z., Jiang, S., Wang, Y., & Li, W. (2022). Icariin exhibits protective effects on cisplatin-induced cardiotoxicity via ROSmediated oxidative stress injury in vivo and in vitro. Phytomedicine, 104, 154331. https://doi.org/10.1016/j.phymed.2022.154331
  24. Yovas, A., Stanely, S. P., & Ponnian, S. M. P. (2023). Protective effects of β-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats. European Journal of Pharmacology, 952, 175785. https://doi.org/10.1016/j.ejphar.2023.175785
  25. Zhang, H., & Xu, J. (2024). Unveiling thioacetamide-induced toxicity: Multi-organ damage and omitted bone toxicity. Human and Experimental Toxicology, 43, 096032712412418. https://doi.org/10.1177/096032712412418