Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice

Journal of Translational Medicine

Hongqian Guo²  Xiaoping Gu⁴  Shiwei Zhang²  Yimin Yuan²  Yanting Zhang³  Xiaozhi Zhao¹  Kai Fu¹  Xuefeng Qiu³ 

[1] Institute of Urology, Nanjing University, Nanjing 210093, China;Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China;State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;Department of Anesthesiology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China

关键词: Antioxidant;    Astaxanthin;    Oxidative stress;    Ischemia/reperfusion;    Kidney;    Renal transplantation;   

Others  :  1139238
DOI  :  10.1186/s12967-015-0388-1

 received in 2014-12-05, accepted in 2015-01-12,  发布年份 2015

【 摘 要 】

Astaxanthin (ATX) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. Previous studies have shown that ATX has effects of eliminating oxygen free radicals and can protect organs from ischemia/reperfusion (IR) induced injury. The present study was designed to further investigate the protective effects of ATX on oxidative stress induced toxicity in tubular epithelial cells and on IR induced renal injury in mice. ATX, at a concentration of 250 nM, attenuated 100 μM H₂O₂-inudced viability decrease of tubular epithelial cells. In vivo, ATX preserved renal function 12 h or 24 h post IR. Pretreatment of ATX via oral gavage for 14 consecutive days prior to IR dramatically prevented IR induced histological damage 24 h post IR. Histological results showed that the pathohistological score, number of apoptotic cells, and the expression of α-smooth muscle actin were significantly decreased by pretreatment of ATX. In addition, oxidative stress and inflammation in kidney samples were significantly reduced by ATX 24 h post IR. Taken together, the current study suggests that pretreatment of ATX is effective in preserving renal function and histology via antioxidant activity.

【 授权许可】

   
2015 Qiu et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Stallone G, Infante B, Gesualdo L: Older donors and older recipients in kidney transplantation. J Nephrol 2010, 23(Suppl 15):S98-103.
• [2]Audard V, Matignon M, Dahan K, Lang P, Grimbert P: Renal transplantation from extended criteria cadaveric donors: problems and perspectives overview. Transpl Int 2008, 21:11-7.
• [3]Pratschke J, Kofla G, Wilhelm MJ, Vergopoulos A, Laskowski I, Shaw GD, et al.: Improvements in early behavior of rat kidney allografts after treatment of the brain-dead donor. Ann Surg 2001, 234:732-40.
• [4]Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL: Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 1997, 63:968-74.
• [5]Carden DL, Granger DN: Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000, 190:255-66.
• [6]Devarajan P: Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006, 17:1503-20.
• [7]Perico N, Cattaneo D, Sayegh MH, Remuzzi G: Delayed graft function in kidney transplantation. Lancet 2004, 364:1814-27.
• [8]Lee DB, Huang E, Ward HJ: Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol 2006, 290:F20-34.
• [9]Strutz F, Zeisberg M, Ziyadeh FN, Yang CQ, Kalluri R, Muller GA, et al.: Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney Int 2002, 61:1714-28.
• [10]Drugas GT, Paidas CN, Yahanda AM, Ferguson D, Clemens MG: Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia/reperfusion. Circ Shock 1991, 34:278-83.
• [11]Atalla SL, Toledo-Pereyra LH, MacKenzie GH, Cederna JP: Influence of oxygen-derived free radical scavengers on ischemic livers. Transplantation 1985, 40:584-90.
• [12]Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H: Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod 2006, 69:443-9.
• [13]Guerin M, Huntley ME, Olaizola M: Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol 2003, 21:210-6.
• [14]Palozza P, Krinsky NI: Astaxanthin and canthaxanthin are potent antioxidants in a membrane model. Arch Biochem Biophys 1992, 297:291-5.
• [15]Lim BP, Nagao A, Terao J, Tanaka K, Suzuki T, Takama K: Antioxidant activity of xanthophylls on peroxyl radical-mediated phospholipid peroxidation. Biochim Biophys Acta 1992, 1126:178-84.
• [16]Shibata A, Kiba Y, Akati N, Fukuzawa K, Terada H: Molecular characteristics of astaxanthin and beta-carotene in the phospholipid monolayer and their distributions in the phospholipid bilayer. Chem Phys Lipids 2001, 113:11-22.
• [17]Curek GD, Cort A, Yucel G, Demir N, Ozturk S, Elpek GO, et al.: Effect of astaxanthin on hepatocellular injury following ischemia/reperfusion. Toxicology 2010, 267:147-53.
• [18]Lu YP, Liu SY, Sun H, Wu XM, Li JJ, Zhu L: Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res 2010, 1360:40-8.
• [19]Shen H, Kuo CC, Chou J, Delvolve A, Jackson SN, Post J, et al.: Astaxanthin reduces ischemic brain injury in adult rats. FASEB J 2009, 23:1958-68.
• [20]Lauver DA, Lockwood SF, Lucchesi BR: Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. J Pharmacol Exp Ther 2005, 314:686-92.
• [21]Bischoff A, Bucher M, Gekle M, Sauvant C: Differential effect of COX1 and COX2 inhibitors on renal outcomes following ischemic acute kidney injury. Am J Nephrol 2014, 40:1-11.
• [22]Melnikov VY, Faubel S, Siegmund B, Lucia MS, Ljubanovic D, Edelstein CL: Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest 2002, 110:1083-91.
• [23]Chen YT, Yang CC, Zhen YY, Wallace CG, Yang JL, Sun CK, et al.: Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury. Stem Cell Res Ther 2013, 4:62. BioMed Central Full Text
• [24]Petri D, Lundebye AK: Tissue distribution of astaxanthin in rats following exposure to graded levels in the feed. Comp Biochem Physiol C Toxicol Pharmacol 2007, 145:202-9.
• [25]Kurashige M, Okimasu E, Inoue M, Utsumi K: Inhibition of oxidative injury of biological membranes by astaxanthin. Physiol Chem Phys Med NMR 1990, 22:27-38.
• [26]Pashkow FJ, Watumull DG, Campbell CL: Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 2008, 101:58D-68.
• [27]Fassett RG, Coombes JS: Astaxanthin: a potential therapeutic agent in cardiovascular disease. Mar Drugs 2011, 9:447-65.
• [28]Hay ED, Zuk A: Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995, 26:678-90.
• [29]Badid C, Desmouliere A, Babici D, Hadj-Aissa A, McGregor B, Lefrancois N, et al.: Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction. Nephrol Dial Transplant 2002, 17:1993-8.
• [30]Liu Y: Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 2004, 15:1-12.
• [31]Simone S, Rascio F, Castellano G, Divella C, Chieti A, Ditonno P, et al.: Complement-dependent NADPH oxidase enzyme activation in renal ischemia/reperfusion injury. Free Radic Biol Med 2014, 74:263-73.
• [32]Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK: Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol 2010, 298:F1078-94.