Ratlarda Rosmarinik Asit’in Akut Pankreatit Üzerindeki Koruyucu Etkinliğinin İncelenmesi

Yıl 2022, Cilt: 5 Sayı: 2, 250 - 258, 31.08.2022

Memet Rencber , Abdullah Oğuz , Eda Yildizhan

https://doi.org/10.36516/jocass.1150397

Öz

Amaç: Akut pankreatit her yüz bin kişide 5-35 kişi arasında görülen ciddi bir hastane yatış sebebidir. Hastane yatışlarının yaklaşık yüzde 5-10’u ölümle sonuçlanmaktadır. Pankreatit durumunun tedavisi konusunda her geçen gün yeni çalışmalar planlanmaktır. Rozmarinik asit’in yapılan birçok çalışmada antioksidan özelliğe sahip olduğu gösterilmiştir. Bizde yaptığımız bu çalışmada Rosmarinik asit’in akut pankreatit üzerinde koruyucu etkinliğini incelemeyi amaçladık.
Materyal/ Metod: : Deney süresince toplam 28 hayvan kullanılmış olup, her grupta 7 hayvan olacak şekilde 4 grup oluşturuldu. Grup 1 kontrol grubu olup deney süresince hiçbir ilaç kullanılmadı. Grup 2’deki ratlara saatte bir 75 μg/kg Cerulein birer saat arayla intraperitoneal olarak, toplam dört defa enjekte edildi. Grup 3 deney hayvanlarına peroral gavaj yoluyla 50 mg/kg dozda Rosmarinik asit verildi. Grup 4’deki ratlara ise saatte bir 75 μg/kg Cerulein intraperitoneal olarak toplam dört defa olmak üzere enjekte edildikten sonra, Rosmarinik asit peroral gavaj yoluyla 50 mg/kg verildi. Sonrasında çalışma gruplarındaki tüm hayvanlar ekzanguinasyon ile sakrifiye edildi, kalpten alınan kan örnekleri ve pankreas dokusu inceleme amacıyla alındı.
Bulgular: Pankreas dokularının ışık mikroskobik incelemelerinde akut pankreatit grubunda dokularda nekroz, ödem ve inflamasyon görüldü. Rosmarinik asit grubunun hem histopatolojik hem de serum değerlerinin kontrol grubuna yakın olduğu görüldü. Akut pankreatit sonrası Rosmarinik asit kullanımının pakreas dokularda ve kan değerlerinde pozitif etkili olduğu, fakat yine de tamamen iyileşmeye neden olmadığı tespit edildi.
Sonuç: Akut pankreatit durumunda Rosmarinik asitin kısmen iyileştirici özelliğinin olduğu fakat yine de tam bir iyileşme sağlamadığı kanaatine varıldı.

Anahtar Kelimeler

Akut pankreatit, Cerulein, Rosmarinik Asit

Protective Efficacy of Rosmarinic Acid on Acute Pancreatitis in Rats

Öz

Abstract
Aim: Acute pancreatitis is a serious disease, with an incidence of 5 - 35 in 100,000 individual. New studies are constantly planned for the treatment of pancreatitis. Many studies have shown that Rosmarinic acid has antioxidant properties. In this study, we examined the protective effect of Rosmarinic acid on acute pancreatitis.
Material and Methods: A total of 28 animals were used during the experiment, and 4 groups were formed with 7 animals in each group. Group 1 is the control group. The rats in Group 2 were administered 75 μg/kg Cerulein every hour intraperitoneally at one hour intervals, a total of four times. Group 3 experimental animals were given 50 mg/kg Rosmarinic acid by per oral gavage. The rats in group 4 were given 50 mg/kg Rosmarinic acid per oral gavage after 75 μg/kg Cerulein was injected intraperitoneally every hour for a total of four times. Afterwards, all animals were sacrificed by exsanguination, blood samples and pancreatic tissue were taken for examination.
Results: Examination of pancreatic tissues revealed necrosis, edema and inflammation in the acute pancreatitis group. Both histopathological and serum values of the rosmarinic acid group were close to the control group. The use of Rosmarinic acid after acute pancreatitis had a positive effect on the pacreatic tissues and blood values, but still did not cause complete recovery.
Conclusion: In the case of acute pancreatitis, it was concluded that rosmarinic acid has a partial curative effect, but still does not provide a full recovery.

Anahtar Kelimeler

Acute pancreatitis, Cerulein, Rosmarinic Acid

Kaynakça

• 1. Saluja AK, Steer ML. Pathophysiology of pancreatitis. Digestion . 1999;60:27–33.
• 2. Bhatia M. · Wong F.L. · Cao Y. · Lau H.Y. · Huang J. · Puneet P. · Chevali L. Pathophysiology of Acute Pancreatitis. Pancreatology 2005;5:132–144.
• 3. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 ;62(1):102-111.
• 4. Han S, Yang S, Cai Z, et al. Anti-Warburg effect of rosmarinic acid via miR-155 in gastric cancer cells.Drug Des Devel Ther. 2015; 9: 2695–2703.
• 5. Miranda LE, Capellini VK, Reis GS, et al. Effects of partial liver ischemia followed by global liver reperfusion on the remote tissue expression of nitric oxide synthase: lungs and kidneys. Transplant Proc. 2010; 42(5): 1557–1562.
• 6. Xu Y, Jiang Z, Ji G, et al. Inhibition of bone metastasis from breast carcinoma by rosmarinic acid. Planta Med. 2010; 76(10): 956–962.
• 7. Chu X, Ci X, He J, et al. Effects of a natural prolyl oligopeptidase inhibitor, rosmarinic acid, on lipopolysaccharide-induced acute lung injury in mice. Molecules. 2012; 17(3): 3586–3598.
• 8. Xu Y, Xu G, Liu Li, et al. Anti-invasion effect of rosmarinic acid via the extracellular signal regulated kinase and oxidation- reduction pathway in Ls174-T cells. J Cell Biochem. 2010; 111(2): 370–379.
• 9. Moon DO, Kim MO, Lee JD, et al. Rosmarinic acid sensitizes cell death through suppression of TNF-alpha-induced NF-kappaB activation and ROS generation in human leukemia U937 cells. Cancer Lett. 2010; 288(2): 183–191.
• 10. Schoenberg M H, Büchler M, Gaspar M, Stinner A. Oxygen free radicals in acute pancreatits of the rat. Gut 1990; 31: 1138-1143.
• 11. Erel O: A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 2004; 37: 112–19
• 12. Erel O: A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 2005; 38: 1103–11
• 13.Tüfek A, Tokgöz O, Aliosmanoglu I, Alabalik U, Evliyaoglu O, Çiftçi T, et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg. 2013;11(1):96–100
• 14.Irrera, N., Bitto, A., Interdonato, M., Squadrito, F., Altavilla, D. Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis. World J. Gastroenterol. 2014; 20 (44): 16535–16543.
• 15. Kambhampati, S., Park, W., Habtezion, A. Pharmacologic therapy for acute pancreatitis. World J. Gastroenterol. 2014;20 (45): 16868–16880.
• 16. Fan, Y. T., Yin, G. J., Xiao, W. Q., Qiu, L., Yu, G., Hu, Y. L., et al. Rosmarinic acid attenuates sodium taurocholate-induced acute pancreatitis in rats by inhibiting nuclear factor-kappaB activation. Am. J. Chin. Med. 2015; 43 (6): 1117–1135
• 17. Luo C, Zou L, Sun H, Peng J, Gao C, Bao L, Ji R, Jin Y, Sun S. A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases. Front Pharmacol. 2020; 28 (11):153
• 18. McCue, P. P., & Shetty, K. Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro. Asia Pacific Journal of Clinical Nutrition. 2004;13: 1.
• 19. Alagawany, M., Abd El-Hack, M. E., Farag, M. R., Gopi, M., Karthik, K., Malik, Y. S., & Dhama, K. Rosmarinic acid: modes of action, medicinal values and health benefits. Animal Health Research Reviews, 2017;18(2): 167-176.
• 20.J. Norman, “The role of cytokines in the pathogenesis of acute pancreatitis,” The American Journal of Surgery. 1998; 175 (1):76–83
• 21. Seyed Abbas M, AB, Hassan Y, Bahareh K, Yekta P, Seyed AST, Soheila YD, Tina P, Ehsan S and Ehsan J. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat. Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity. 2016; 2016: 8
• 22. Ramalho, L. N. Z., Pasta, Â. A. C., Terra, V. A., Augusto, M. J., Sanches, S. C., Souza-Neto, F. P., ... & Ramalho, F. S. Rosmarinic acid attenuates hepatic ischemia and reperfusion injury in rats. Food and chemical toxicology. 2014; 74: 270-278.
• 23. Ahmed, M. M. Rosmarinic acid attenuates the hepatotoxicity induced by ethanol in rats. American Journal of Biochemistry. 2016; 6(3): 82-90.
• 24. Oğuz A, Böyük A, Ekinci A, Alabalik U, Türkoğlu A, Tuncer MC& Aday U. Investigation of antioxidant effects of rosmarinic acid on liver, lung and kidney in rats: a biochemical and histopathological study. Folia morphologica. 2020; 79 (2): 288-295.
• 25. Sadeghi, A., Bastin, A. R., Ghahremani, H., & Doustimotlagh, A. H. The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells. Molecular biology reports. 2020; 47(5): 3557-3566.
• 26. Ilhan N, Bektas I, Susam S, Ozercan IH. Protective effects of rosmarinic acid against azoxymethane-induced colorectal cancer in rats. J Biochem Mol Toxicol. 2021;12:e22961
• 27.Mohammed FS, Karakas M, Akgul H, Sevindik M. Medıcınal propertıes of a ıu aоp collected from gara mountaın (ıraq). feb-fresenıus envıronmental bulletın. 2019; 26 (7): 4757-4763