BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Renal protective effects of zingerone in a mouse model of sepsis

  • Lee, Bong-Seon (College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University) ;
  • Lee, Changhun (College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University) ;
  • Yang, Sumin (College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University) ;
  • Ku, Sae-Kwang (Department of Histology and Anatomy, College of Korean Medicine, Daegu Haany University) ;
  • Bae, Jong-Sup (College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University)
  • 투고 : 2018.07.27
  • 심사 : 2018.08.30
  • 발행 : 2019.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess pharmacological activities such as anti-inflammatory and anti-apoptotic effects. This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR inhibited nuclear $factor-{\kappa}B$ activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. ZGR treatment also reduced the plasma levels of interleukin-6 and tumor necrosis $factor-{\alpha}$, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. Our study showed renal suppressive effects of zingerone in a mouse model of sepsis, suggesting that ZGR protects mice against sepsis-triggered renal injury.

키워드

참고문헌

  1. Russell JA (2006) Management of sepsis. N Engl J Med 355, 1699-1713 https://doi.org/10.1056/NEJMra043632
  2. Singer M, Deutschman CS, Seymour CW et al (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801-810 https://doi.org/10.1001/jama.2016.0287
  3. Chaudhry H, Zhou J, Zhong Y et al (2013) Role of cytokines as a double-edged sword in sepsis. In Vivo 27, 669-684
  4. Parratt JR (1998) Nitric oxide in sepsis and endotoxaemia. J Antimicrob Chemother 41 Suppl A, 31-39 https://doi.org/10.1093/jac/41.suppl_1.31
  5. Symeonides S and Balk RA (1999) Nitric oxide in the pathogenesis of sepsis. Infect Dis Clin North Am 13, 449-463, x https://doi.org/10.1016/S0891-5520(05)70085-4
  6. Draisma A, Dorresteijn MJ, Bouw MP, van der Hoeven JG and Pickkers P (2010) The role of cytokines and inducible nitric oxide synthase in endotoxemia-induced endothelial dysfunction. J Cardiovasc Pharmacol 55, 595-600 https://doi.org/10.1097/FJC.0b013e3181da774b
  7. Vincent JL, Zhang H, Szabo C and Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161, 1781-1785 https://doi.org/10.1164/ajrccm.161.6.9812004
  8. Cadenas S and Cadenas AM (2002) Fighting the stranger-antioxidant protection against endotoxin toxicity. Toxicology 180, 45-63 https://doi.org/10.1016/S0300-483X(02)00381-5
  9. Park KK, Chun KS, Lee JM, Lee SS and Surh YJ (1998) Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett 129, 139-144 https://doi.org/10.1016/S0304-3835(98)00081-0
  10. Sies H and Masumoto H (1997) Ebselen as a glutathione peroxidase mimic and as a scavenger of peroxynitrite. Adv Pharmacol 38, 229-246 https://doi.org/10.1016/S1054-3589(08)60986-2
  11. Lee W, Ku SK and Bae JS (2017) Zingerone reduces HMGB1-mediated septic responses and improves survival in septic mice. Toxicol Appl Pharmacol 329, 202-211 https://doi.org/10.1016/j.taap.2017.06.006
  12. Kim MK, Chung SW, Kim DH et al (2010) Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway. Exp Gerontol 45, 419-426 https://doi.org/10.1016/j.exger.2010.03.005
  13. Rao BN, Archana PR, Aithal BK and Rao BS (2011) Protective effect of zingerone, a dietary compound against radiation induced genetic damage and apoptosis in human lymphocytes. Eur J Pharmacol 657, 59-66 https://doi.org/10.1016/j.ejphar.2011.02.002
  14. Hemalatha KL and Prince PS (2015) Preventive effects of zingerone on altered lipid peroxides and nonenzymatic antioxidants in the circulation of isoproterenol-induced myocardial infarcted rats. J Biochem Mol Toxicol 29, 63-69 https://doi.org/10.1002/jbt.21668
  15. Banji D, Banji OJ, Pavani B, Kranthi Kumar C and Annamalai AR (2014) Zingerone regulates intestinal transit, attenuates behavioral and oxidative perturbations in irritable bowel disorder in rats. Phytomedicine 21, 423-429 https://doi.org/10.1016/j.phymed.2013.10.007
  16. Lee IC, Kim DY and Bae JS (2017) Inhibitory Effect of Zingerone on Secretory Group IIA Phospholipase A2. Nat Prod Commun 12, 929-932
  17. Lee W, Ku SK, Kim MA and Bae JS (2017) Anti-factor Xa activities of zingerone with anti-platelet aggregation activity. Food Chem Toxicol 105, 186-193 https://doi.org/10.1016/j.fct.2017.04.012
  18. Agca CA, Tuzcu M, Hayirli A and Sahin K (2014) Taurine ameliorates neuropathy via regulating NF-kappaB and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 71, 116-121 https://doi.org/10.1016/j.fct.2014.05.023
  19. Yu M, Xu M, Liu Y et al (2013) Nrf2/ARE is the potential pathway to protect Sprague-Dawley rats against oxidative stress induced by quinocetone. Regul Toxicol Pharmacol 66, 279-285 https://doi.org/10.1016/j.yrtph.2013.04.005
  20. Huber-Lang M, Sarma VJ, Lu KT et al (2001) Role of C5a in multiorgan failure during sepsis. J Immunol 166, 1193-1199 https://doi.org/10.4049/jimmunol.166.2.1193
  21. Bhargava R, Altmann CJ, Andres-Hernando A et al (2013) Acute lung injury and acute kidney injury are established by four hours in experimental sepsis and are improved with pre, but not post, sepsis administration of TNF-alpha antibodies. PLoS One 8, e79037 https://doi.org/10.1371/journal.pone.0079037
  22. Guo RF and Ward PA (2006) C5a, a therapeutic target in sepsis. Recent Pat Antiinfect Drug Discov 1, 57-65 https://doi.org/10.2174/157489006775244272
  23. Stearns-Kurosawa DJ, Osuchowski MF, Valentine C, Kurosawa S and Remick DG (2011) The pathogenesis of sepsis. Annu Rev Pathol 6, 19-48 https://doi.org/10.1146/annurev-pathol-011110-130327
  24. Oeckinghaus A and Ghosh S (2009) The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1, a000034 https://doi.org/10.1101/cshperspect.a000034
  25. Birben E, Sahiner UM, Sackesen C, Erzurum S and Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5, 9-19 https://doi.org/10.1097/WOX.0b013e3182439613
  26. Horton JW (2003) Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy. Toxicology 189, 75-88 https://doi.org/10.1016/S0300-483X(03)00154-9
  27. Hatwalne MS (2012) Free radical scavengers in anaesthesiology and critical care. Indian J Anaesth 56, 227-233 https://doi.org/10.4103/0019-5049.98760
  28. Qiao Y, Bai XF and Du YG (2011) Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress. Int Immunopharmacol 11, 121-127 https://doi.org/10.1016/j.intimp.2010.10.016
  29. Zhang J, Yu Y, Zhang Z, Ding Y, Dai X and Li Y (2011) Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to 60Co. Int Immunopharmacol 11, 2251-2257 https://doi.org/10.1016/j.intimp.2011.09.019
  30. Xiao JH, Xiao DM, Chen DX, Xiao Y, Liang ZQ and Zhong JJ (2012) Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model. Evid Based Complement Alternat Med 2012, 273435
  31. Jung B, Kang H, Lee W et al (2016) Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses. BMB Rep 49, 214-219 https://doi.org/10.5483/BMBRep.2016.49.4.220
  32. Wang H, Liao H, Ochani M et al (2004) Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 10, 1216-1221 https://doi.org/10.1038/nm1124
  33. Miranda KM, Espey MG and Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5, 62-71 https://doi.org/10.1006/niox.2000.0319
  34. Beutler E, Duron O and Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61, 882-888
  35. Kim J and Bae JS (2016) ROS homeostasis and metabolism: a critical liaison for cancer therapy. Exp Mol Med 48, e269 https://doi.org/10.1038/emm.2016.119