대한약침학회지 (Journal of Pharmacopuncture)

  • 제27권3호
  • /
  • Pages.245-252
  • /
  • 2024
  • /
  • 2093-6966(pISSN)
  • /
  • 2234-6856(eISSN)
대한약침학회 (KOREAN PHARMACOPUNCTURE INSTITUTE)
권호 표지
DOI QR코드

DOI QR Code

Comparative Study of the Protective Effects of Citral, Thymoquinone, and Silymarin on Methotrexate-induced Cardiotoxicity in Rats

  • Barzan Behdokht (Department of Basic Sciences, School of Veterinary Medicine, Shiraz University) ;
  • Noorbakhsh Mohammad Foad (Department of Basic Sciences, School of Veterinary Medicine, Shiraz University) ;
  • Nazifi Saeed (Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University) ;
  • Nasrollah Ahmadi (Department of Pathobiology, School of Veterinary Medicine, Shiraz University) ;
  • Amani Sakineh (Department of Basic Sciences, School of Veterinary Medicine, Shiraz University)
  • 투고 : 2024.04.11
  • 심사 : 2024.06.05
  • 발행 : 2024.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives: Methotrexate (MTX), an immunosuppressant and anti-cancer medication, can harm the heart. The goal of the current investigation was to assess the cardiotoxicity caused by MTX and the potential cardioprotective properties of silymarin, citral, and thymoquinone as antioxidants. Methods: Forty-eight rats were divided into six groups, which included control, MTX, cosolvent, citral, thymoquinone, and silymarin groups. At the end of the study, the rats were anesthetized (ketamine and xylazine) and killed using CO2. Their blood samples were collected to measure the enzymatic activities of creatine kinase-myoglobin binding (CK-MB), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Also, the heart tissue was sampled to determine the antioxidant capacity and examine the histopathology. Results: The findings revealed that the activity of CPK, CK-MB, and LDH enzymes significantly reduced in the thymoquinone treatment group compared to the MTX group (p < 0.05). On the other hand, total antioxidant capacity was significantly increased in the thymoquinone group compared to the MTX group (p < 0.05). The pathological modifications (i.e. severe congestion, edema fluid, the presence of inflammatory cells around the blood vessels, mild to moderate hemorrhaging between cardiac muscle fibers) were seen in the MTX group. The treatment groups, particularly thymoquinone, did not experience any appreciable pathological changes. Conclusion: The thymoquinone was found to have the strongest protective effect against the heart damage caused by MTX.

키워드

과제정보

I thank Dr. Jafar Jalai for his cooperation in the implementation of this project.

참고문헌

  1. Chaudhari R, Patel P, Meghani N, Nasra S, Kumar A. Fabrication of methotrexate-loaded gold nanoconjugates and its enhanced anticancer activity in breast cancer. 3 Biotech. 2021;11(4):175. 
  2. Lui SW, Lu JW, Ho YJ, Hsieh TY, Yeh FC, Liu FC. IVIG as a promising therapy for methotrexate-induced life-threatening neutropenic enterocolitis in an elderly patient with rheumatoid arthritis: a case report and literature review. In Vivo. 2024;38(1):511-7. 
  3. Sramek M, Neradil J, Veselska R. Much more than you expected: the non-DHFR-mediated effects of methotrexate. Biochim Biophys Acta Gen Subj. 2017;1861(3):499-503. 
  4. El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediators Inflamm. 2015;2015:859383. 
  5. Perez-Verdia A, Angulo F, Hardwicke FL, Nugent KM. Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature. Pharmacotherapy. 2005;25(9):1271-6. 
  6. Mahmoud RH, Mohammed MA, Said ES, Morsi EM, Abdelaleem OO, Abdel All MO, et al. Assessment of the cardioprotective effect of liraglutide on methotrexate induced cardiac dysfunction through suppression of inflammation and enhancement of angiogenesis in rats. Eur Rev Med Pharmacol Sci. 2021;25(19):6013-24. 
  7. Al-Abkal F, Abdel-Wahab BA, El-Kareem HFA, Moustafa YM, Khodeer DM. Protective effect of pycnogenol against methotrexate-induced hepatic, renal, and cardiac toxicity: an in vivo study. Pharmaceuticals (Basel). 2022;15(6):674. 
  8. Sharma S, Habib S, Sahu D, Gupta J. Chemical properties and therapeutic potential of citral, a monoterpene isolated from lemongrass. Med Chem. 2021;17(1):2-12. 
  9. Uchida NS, Silva-Filho SE, Cardia GFE, Cremer E, Silva-Comar FMS, Silva EL, et al. Hepatoprotective effect of citral on acetaminophen-induced liver toxicity in mice. Evid Based Complement Alternat Med. 2017;2017:1796209. 
  10. Lu Y, Feng Y, Liu D, Zhang Z, Gao K, Zhang W, et al. Thymoquinone attenuates myocardial ischemia/reperfusion injury through activation of SIRT1 signaling. Cell Physiol Biochem. 2018;47(3):1193-206. 
  11. Ran J, Xu H, Li W. Cardioprotective effects of co-administration of thymoquinone and ischemic postconditioning in diabetic rats. Iran J Basic Med Sci. 2021;24(7):892-9. 
  12. De Marco A, Luongo G, Di Marino C, De Tommaso G, Di Fabio G, Zarrelli A. Silymarin from Silybum marianum by Naviglio's extractor: a new and very efficient approach. Nat Prod Res. 2021;35(15):2621-7. 
  13. Shah SMA, Akram M, Riaz M, Munir N, Rasool G. Cardioprotective potential of plant-derived molecules: a scientific and medicinal approach. Dose Response. 2019;17(2):1559325819852243. 
  14. Li CC, Yu HF, Chang CH, Liu YT, Yao HT. Effects of lemongrass oil and citral on hepatic drug-metabolizing enzymes, oxidative stress, and acetaminophen toxicity in rats. J Food Drug Anal. 2018;26(1):432-8. 
  15. Shen Y, Sun Z, Guo X. Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ. Eur J Pharmacol. 2015;747:45-51. 
  16. Razavi-Azarkhiavi K, Ali-Omrani M, Solgi R, Bagheri P, Haji-Noormohammadi M, Amani N, et al. Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice. Pharm Biol. 2014;52(10):1267-71. 
  17. Boskabady M, Khazdair MR, Bargi R, Saadat S, Memarzia A, Mohammadian Roshan N, et al. Thymoquinone ameliorates lung inflammation and pathological changes observed in lipopolysaccharide-induced lung injury. Evid Based Complement Alternat Med. 2021;2021:6681729. 
  18. Danaei GH, Memar B, Ataee R, Karami M. Protective effect of thymoquinone, the main component of Nigella Sativa, against diazinon cardio-toxicity in rats. Drug Chem Toxicol. 2019;42(6):585-91. 
  19. El-Sheikh AA, Morsy MA, Hamouda AH. Protective mechanisms of thymoquinone on methotrexate-induced intestinal toxicity in rats. Pharmacogn Mag. 2016;12(Suppl 1):S76-81. 
  20. Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res. 2000;41(3):283-9. 
  21. Shirmard LR, Shabani M, Moghadam AA, Zamani N, Ghanbari H, Salimi A. Protective effect of curcumin, chrysin and thymoquinone injection on trastuzumab-induced cardiotoxicity via mitochondrial protection. Cardiovasc Toxicol. 2022;22(7):663-75. 
  22. Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S, et al. Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in swiss albino mice by modulating oxidative damage and cellular inflammation. Cardiol Res Pract. 2018;2018:1483041. 
  23. Hafez AA, Jamali Z, Khezri S, Salimi A. Thymoquinone reduces mitochondrial damage and death of cardiomyocytes induced by clozapine. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(8):1675-84. 
  24. Cengiz MZ. Renoprotective effects of Silybum marianum (L.) Gaertn (Silymarin) on thioacetamide-induced renal injury: biochemical and histopathological approach. Pak J Pharm Sci. 2018;31(5(Supplementary)):2137-41. 
  25. Avci H, Epikmen ET, Ipek E, Tunca R, Birincioglu SS, Aksit H, et al. Protective effects of silymarin and curcumin on cyclophosphamide-induced cardiotoxicity. Exp Toxicol Pathol. 2017;69(5):317-27. 
  26. Ipek E, Tunca R. Silymarin protects against doxorubicin induced cardiotoxicity by down-regulating topoisomerase IIβ expression in mice. Biotech Histochem. 2023;98(6):412-23. 
  27. Aktas I, Ozgocmen M. The treatment effect of silymarin on heart damage in rats. Ann Med Res. 2020;27(3):948-54. 
  28. Taghiabadi E, Imenshahidi M, Abnous K, Mosafa F, Sankian M, Memar B, et al. Protective effect of silymarin against acrolein-induced cardiotoxicity in mice. Evid Based Complement Alternat Med. 2012;2012:352091. 
  29. Rahimi R, Karimi J, Khodadadi I, Tayebinia H, Kheiripour N, Hashemnia M, et al. Silymarin ameliorates expression of urotensin II (U-II) and its receptor (UTR) and attenuates toxic oxidative stress in the heart of rats with type 2 diabetes. Biomed Pharmacother. 2018;101:244-50. 
  30. Phillips JC, Kingsnorth J, Gangolli SD, Gaunt IF. Studies on the absorption, distribution and excretion of citral in the rat and mouse. Food Cosmet Toxicol. 1976;14(6):537-40. 
  31. Safaeian L, Sajjadi SE, Montazeri H, Ohadi F, Javanmard S. Citral protects human endothelial cells against hydrogen peroxideinduced oxidative stress. Turk J Pharm Sci. 2020;17(5):549-54. 
  32. Yardimci M, Goz M, Aydin MS, Kankilic N, Temiz E. Antioxidant actions of thymoquinone, silymarin, and curcumin on experimental aortic ischemia-reperfusion model in Wistar albino rats. Braz J Cardiovasc Surg. 2022;37(6):807-13.