The Antioxidant Effect of Fraxin against Acute Organ Damage in Polymicrobial Sepsis Model induced by Cecal Ligation and Puncture

Abstract

Aim: In this paper, it was purposed to evaluate the antioxidant effect of fraxin against acute organ
damage induced by cecal ligation and puncture model (CLP) in rats. Material and Methods: For this
purpose in our study, all experimental animals were randomly grouped. These groups were stated as shamcontrol, CLP, CLP+Fraxin 50 mg/kg, CLP+Fraxin 100 mg/kg groups. TAS, TOS, OSI, MDA levels, MPO
and SOD activities were evaluated in kidney and lung tissues of all rats. Results: TOS, OSI, MDA levels and
MPO activity of kidney and lung tissues were higher in the CLP group than in the sham-control group, but
TAS level and SOD activity were lower. However, these results were significantly changed in the fraxin
treatment groups. Conclusion: In light of these results, it can be stated that fraxin shows a positive effect by
raising the level of SOD and TAS by decreasing TOS, MPO and MDA levels on kidney and lung tissue in the
model of sepsis caused by CLP.

Keywords

• Cecal ligation and puncture
• fraxin
• sepsis
• rat

Kaynakça

1. 1.Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-Journal of the American Medical Association 2016,315:775-787.
2. 2.Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama-Journal of the American Medical Association 2016,315:801-810.
3. 3.Bastarache JA, Matthay MA. Cecal ligation model of sepsis in mice: new insights. Crit Care Med 2013,41:356-357.
4. 4.Song LL, Zou YJ, Cao ZP. Comparison of two different models of sepsis induced by cecal ligation and puncture in rats. Journal of Surgical Research 2018,229:277-282.
5. 5.Cadirci E, Altunkaynak BZ, Halici Z, Odabasoglu F, Uyanik MH, Gundogdu C, et al. alpha-LIPOIC ACID AS A POTENTIAL TARGET FOR THE TREATMENT OF LUNG INJURY CAUSED BY CECAL LIGATION AND PUNCTURE-INDUCED SEPSIS MODEL IN RATS. Shock 2010,33:479-484.
6. 6.Cinar I, Sirin B, Aydin P, Toktay E, Cadirci E, Halici I, et al. Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life Sci 2019.
7. 7.Kostova I. Fraxinus ornus L. Fitoterapia 2001,72:471-480.
8. 8.Niu X, Liu F, Li W, Zhi W, Yao Q, Zhao J, et al. Hepatoprotective effect of fraxin against carbon tetrachloride-induced hepatotoxicity in vitro and in vivo through regulating hepatic antioxidant, inflammation response and the MAPK-NF-kappaB signaling pathway. Biomed Pharmacother 2017,95:1091-1102.

9. 9.Wang HD, Xiao BX, Hao ZQ, Sun ZX. Simultaneous determination of fraxin and its metabolite, fraxetin, in rat plasma by liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences 2016,1017:70-74.
10. 10.Liu AD, Wang WJ, Fang HS, Yang Y, Jiang XJ, Liu SP, et al. Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice. European Journal of Pharmacology 2015,748:45-53.
11. 11.Otero-Anton E, Gonzalez-Quintela A, Lopez-Soto A, Lopez-Ben S, Llovo J, Perez LF. Cecal ligation and puncture as a model of sepsis in the rat: Influence of the puncture size on mortality, bacteremia, endotoxemia and tumor necrosis factor alpha levels. European Surgical Research 2001,33:77-79.
12. 12.Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982,78:206-209.
13. 13.Ohkawa H, Ohishi N, Yagi K. Assay for Lipid Peroxides in Animal-Tissues by Thiobarbituric Acid Reaction. Analytical Biochemistry 1979,95:351-358.
14. 14.Sun Y, Oberley LW, Li Y. A Simple Method for Clinical Assay of Superoxide-Dismutase. Clinical Chemistry 1988,34:497-500.
15. 15.Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. Chest 1992,101:1644-1655.
16. 16.Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012,81:442-448.
17. 17.Ozdulger A, Cinel I, Koksel O, Cinel L, Avlan D, Unlu A, et al. The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model. Shock 2003,19:366-372.
18. 18.Polat G, Ugan RA, Cadirci E, Halici Z. Sepsis and Septic Shock: Current Treatment Strategies and New Approaches. Eurasian J Med 2017,49:53-58.
19. 19.Gacar N, Gocmez S, Utkan T, Gacar G, Komsuoglu I, Tugay M, et al. Effects of Resveratrol on Ileal Smooth Muscle Reactivity in Polymicrobial Sepsis Model. Journal of Surgical Research 2012,174:339-343.
20. 20.Pereira RS, Bertoncheli CM, Adefegha SA, Castilhos LG, Silveira KL, Rezer JFP, et al. Sepsis induced by cecal ligation and perforation (CLP) alters nucleotidase activities in platelets of rats. Microbial Pathogenesis 2017,111:345-351.
21. 21.Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004,351:159-169.
22. 22.Bedirli A, Kerem M, Pasaoglu H, Akyurek N, Tezcaner T, Elbeg S, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock 2007,27:397-401.
23. 23.Wu LP, Gokden N, Mayeux PR. Evidence for the role of reactive nitrogen species in polymicrobial sepsis-induced renal peritubular capillary dysfunction and tubular injury. Journal of the American Society of Nephrology 2007,18:1807-1815.
24. 24.Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxidative Medicine and Cellular Longevity 2016.
25. 25.Droge W. Free radicals in the physiological control of cell function. Physiological Reviews 2002,82:47-95.
26. 26.Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased Antioxidant Status and Increased Lipid-Peroxidation in Patients with Septic Shock and Secondary Organ Dysfunction. Critical Care Medicine 1995,23:646-651.
27. 27.Wang WP, Yan XL, Ni YF, Guo K, Ke CK, Cheng QS, et al. Effects of Lipid Emulsions in Parenteral Nutrition of Esophageal Cancer Surgical Patients Receiving Enteral Nutrition: A Comparative Analysis. Nutrients 2014,6:111-123.
28. 28.Podrez EA, Abu-Soud HM, Hazen SL. Myeloperoxidase-generated oxidants and atherosclerosis. Free Radic Biol Med 2000,28:1717-1725.
29. 29.Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Med Sci (Basel) 2018,6.
30. 30.Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry 2004,37:277-285.
31. 31.Erel O. A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry 2005,38:1103-1111.
32. 32.Ghiselli A, Serafini M, Natella F, Scaccini C. Total antioxidant capacity as a tool to assess redox status: Critical view and experimental data. Free Radical Biology and Medicine 2000,29:1106-1114.