Musa TURGUT, Halil KOCAMAZ, Esin AVCI, Mutlu YAKA, Gülçin Abban METE

Kaempferol, kurkumin ve kaempferol-kurkumin kombinasyonunun deneysel akut pankreatitteki etkileri

Amaç: Akut Pankreatit ani başlayan karın ağrısı ile kendini gösterip sistemik inflamatuar yanıta kadar ilerleyebilen acil bir klinik durumdur. Standart bir tedavisi olmayan bu hastalıkta güncel tedavi yaklaşımlarına gereksinim vardır. Deneysel akut pankreatitte kaempferol, kurkumin ve kaempferol-kurkumin kombinasyonunun etkilerini göstermeyi amaçladık. Gereç ve Yöntem: Wistar albino erişkin ratlar altı gruba ayrıldı. Grup I: Sıçanlara fizyolojik su intraperitoneal (i.p.) olarak verildi. Grup II: L-arjinin i.p. olarak 250 mg/100 gr, Grup III(DMSO): İ.p. olarak 1 ml/100 gr Dimetil sülfoksit (DMSO), Grup IV(L-Arjinin + Kurkumin): i.p. L-Arginin ve kurkumin 50 mg/kg İP, Grup V(L-Arjinin + Kaempferol): İ.p. L-Arginin ve kaempferol 21 mg/kg İP, Grup VI(L-Arjinin + Kurkumin + Kaempferol): İ.p. L-Arginin , kurkumin 50 mg/kg ve kaempferol 21 mg/kg i.p. uygulandı. Deney bitiminde kan ve pankreas örnekleri alındı. Histolojik, biyokimyasal ve immunohistokimyasal incelemeler yapıldı. Bulgular: Malondialdehid, TNF-α ve IL-6 düzeyleri gruplar arasında farklı değildi. Superoksit dismutaz(SOD) düzeyleri grup VI’da diğer gruplara göre yüksekti ancak istatistiksel olarak anlamlı değildi. Ödem skoru grup VI’da grup II’ye göre daha düşük idi. Grup V ve grup VI’da inflamasyon skoru grup II’ den daha az idi. Nekroz skoru grup IV, grup V ve grup VI’da grup II’den daha az idi. Grup II’deki NF(nükleer faktör)-κB boyanma skoru tedavi gruplarından farklı değildi. Sonuç: L-arjinin ile oluşturulan deneysel akut pankreatitde kaempferolün ve kaempferol-kurkumin kombinasyonunun özellikle histopatolojik olarak inflamasyonu ve nekrozu azalttığı bu sayede koruyucu etkileri olduğu görülmüştür.

Anahtar Kelimeler:

arjinin, kurkumin, inflamasyon

The ameliorative effects of kaempferol, curcumin and kaempferol-curcumin combination on experimental acute pancreatitis

Aim: Acute pancreatitis is a medical emergency disorder which manifests itself with sudden onset abdominal pain and may progress systemic inflammatory response syndrome. Novel treatment modalities are required for this disorder which does not have standard treatment regime. We aimed to evaluate the effects of kaempferol, curcumin and kaempferol-curcumin combination on experimental acute pancreatitis.Material and method: Wistar albino adult rats were divided into 6 groups. Group I: saline was given by intraperitoneal(ip). Group II: L-arginine was given by ip at a dose of 250 mg per 100 gr. Group III(DMSO): Dimethyl sulphoxide (DMSO) was given by ip at a dose of 1 ml/100 gr. Group IV(L-arginine+curcumin): L-arginine and curcumin at a dose of 50 mg/kg was given by ip, Group V(L-arginine+ Kaempferol): L-arginine and kaempferol at a dose of 21 mg/kg was given by ip. Group VI(L-arginine+curcumin + Kaempferol): L-arginine, curcumin at a dose of 50 mg/kg and kaempferol at a dose of 21 mg/kg was given by ip. Blood and pancreas sample of the rats were obtained. Results: Malondialdehyde and IL-6 levels were not different between groups. Superoxide dismutase(SOD) levels were higher than other groups but it was not statistically significant. Edema score on pancreas tissue were lower than group II in group VI. Inflammatıon score were lower than group II in groups V and VI. NF(nuclear factor)- κB staining score were not different between groups. Conclusion: Kaempferol and kaempferol-curcumin combination have protective effects on L-arginine induced experimental acute pancreatitis by diminishing inflammation and necrosis.

Keywords:

arginine, curcumin, inflammation,

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1. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas 2006;33:323-330.
2. Cavestro GM, Leandro G, Di Leo M, Zuppardo RA, Morrow OB, Notaristefano C, Rossi G, et al. A single‑centre prospective, cohort study of the natural history of acute pancreatitis. Dig Liver Dis 2015;47:205‑210.
3. Criddle DN, McLaughlin E, Murphy JA, Petersen OH, Sutton R. The pancreas misled: signals to pancreatitis. Pancreatology 2007;7:436-446.
4. Lundberg AH, Eubanks JW III, Henry J, Sabek O, Kotb M, Gaber L, Gaber AO, et al. Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo. Pancreas 2000;21:41-51.
5. Cuthbertson CM, Christophi C. Disturbances of the microcirculation in acute pancreatitis. Br J Surg 2006;93:518-530.
6. Rakonczay Z Jr, Hegyi P, Takacs T, McCarroll J, Saluja AK. The role of NF-kappa B activation in the pathogenesis of acute pancreatitis. Gut 2008;57:259-267.
7. Forsmark CE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med 2016;375:1972-1981.
8. Phillip V, Steiner JM, Algul H. Early phase of acute pancreatitis: assessment and management. World J Gastrointest Pathophysiol 2014;5:158-168.
9. Vallianou NG, Evangelopoulos A, Schizas N, Kazazis C. Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res 2015;35:645-651.
10. Chen X, Yang X, Liu T, Guan M, Feng X, Dong W, Chu X, et al. Kaempferol regulates MAPKs and NF-kappaB signaling pathways to attenuate LPS-induced acute lung injury in mice. Int Immunopharmacol 2012;14:209-216.
11. Van Laethem JL, Marchant A, Delvaux A, Goldman M, Robberecht P, Velu T, Deviere J. Interleukin-10 prevents necrosis in murine experimental pancreatitis. Gastroenterology 1995;108:1917-1922.
12. Biczó G, Hegyi P, Berczi S, Dósa S, Hracskó Z, Varga IS, Iványi B et al. Inhibition of arginase activity ameliorates L-arginine-induced acute pancreatitis in rats. Pancreas 2010;39:868-874.
13. Vonlaufen A, Apte MV, Imhof BA, Frossard JL. The role of inflammatory and parenchymal cells in acute pancreatitis. J. Pathol 2007;213:239-248.
14. Kim D and Haynes CL. The role of p38 MAPK in neutrophil functions: single cell chemotaxis and surface marker expression. Analyst 2013;138: 6826‑6833.
15. Yu S, Wang M, Guo X and Qin R. Curcumin attenuates inflammation in a severe acute pancreatitis animal model by regulating TRAF1/ASK1 signaling. Med Sci Monit 2018;24:2280‑2286.
16. Jakkampudi A, Jangala R, Reddy BR, Mitnala S, Nageshwar Reddy D, Talukdar R. NF-kappaB in acute pancreatitis: mechanisms and therapeutic potential. Pancreatology 2016;16:477-488.
17. Grewal HP, Mohey el Din A, Gaber L, Kotb M, Gaber AO. Amelioration of the physiologic and biochemical changes of acute pancreatitis using an anti-TNF-alpha polyclonal antibody. Am J Surg 1994;167:218-219.
18. Wang Y, Chanyuan B, Kangkang W, Rui W, and Jiayong W. Curcumin protects the pancreas from acute pancreatitis via the mitogen activated protein kinase signaling pathway. Molecular medicine reports 2019;20: 3027-3034.
19. Tekin SO, Teksoz S, Terzioglu D, Arikan AE, Ozcevik H, Uslu E. Use of infliximab in treatment of acute pancreatitis. Bratisl Lek Listy 2015;116:167-172.
20. Mylroie AA, Collins H, Umbles C, Kyle j. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol 1986;82:512-520.
21. Kim SH, Park JG, Sung GH, Yang S, Yang WS, Kim E, Kim JH, et al. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain. Molecular nutrition & food research 2015;59:1400-1405.