Cerium oxide nanoparticles attenuate acute kidney injury induced by intra-abdominal infection in Sprague–Dawley rats

Journal of Nanobiotechnology

Eric R. Blough¹  Shinichi Asano⁴  Kevin M. Rice⁴  Tolou Shokuhfar³  Niraj Nepal¹  Ravikumar Arvapalli⁴  Nandini D. P. K. Manne² 

[1] Department of Pharmacology, Physiology and Toxicology, Marshall University, Huntington, WV, USA;Department of Pharmaceutical Sciences and Research, Marshall University, Huntington, WV, USA;Department of Mechanical Engineering and Engineering Mechanics, Michigan Technological University, Houghton, MI, USA;Center for Diagnostic Nanosystems, Marshall University, Huntington, WV, USA

关键词: Peritonitis;    Reactive oxygen species;    Acute kidney injury;    Polymicrobial insult;    Cerium oxide nanoparticles;   

Others  :  1231699
DOI  :  10.1186/s12951-015-0135-z

 received in 2015-07-23, accepted in 2015-10-13,  发布年份 2015

【 摘 要 】

Background

Intra-abdominal infection or peritonitis is a cause for great concern due to high mortality rates. The prognosis of severe intra-abdominal infection is significantly diminished in the presence of acute kidney injury (AKI) which is often characterized by renal tubular cell death that can lead to renal failure. The purpose of the current study is to examine the therapeutic efficacy of cerium oxide (CeO ₂ ) nanoparticles for the treatment of peritonitis-induced AKI by polymicrobial insult.

Results

A one-time administration of CeO ₂nanoparticles (0.5 mg/kg) in the absence of antibiotics or other supportive care, attenuated peritonitis-induced tubular dilatation and the loss of brush border in male Sprague–Dawley rats. These improvements in renal structure were accompanied by decreases in serum cystatin-C levels, reduced renal oxidative stress, diminished Stat-3 phosphorylation and an attenuation of caspase-3 cleavage suggesting that the nanoparticle treatment improved renal glomerular filtration rate, diminished renal inflammation and reduced renal apoptosis. Consistent with these data, further analysis demonstrated that the CeO ₂nanoparticle treatment diminished peritonitis-induced increases in serum kidney injury molecule-1 (KIM-1), osteopontin, β-2 microglobulin and vascular endothelial growth factor-A (VEGF-A) levels. In addition, the nanoparticle attenuated peritonitis-induced hyperglycemia along with increases in blood urea nitrogen (BUN), serum potassium and sodium.

Conclusion

CeO ₂nanoparticles scavenge reactive oxygen species and attenuate polymicrobial insult induced increase in inflammatory mediators and subsequent AKI. Taken together, the data indicate that CeO ₂nanoparticles may be useful as an alternative therapeutic agent or in conjunction with standard medical care for the treatment of peritonitis induced acute kidney injury.

【 授权许可】

   
2015 Manne et al.

【 图 表 】

Fig.1.

Fig.2.

Fig.3.

Fig.4.

Fig.5.

Fig.6.

【 参考文献 】

• [1]Majumdar A. Sepsis-induced acute kidney injury. Indian J Crit Care Med Peer-Review Off Publ Indian Soc Crit Care Med. 2010; 14(1):14-21.
• [2]Lee SY, Lee YS, Choi HM, Ko YS, Lee HY, Jo SK et al.. Distinct pathophysiologic mechanisms of septic acute kidney injury: role of immune suppression and renal tubular cell apoptosis in murine model of septic acute kidney injury. Crit Care Med. 2012; 40(11):2997-3006.
• [3]Bougle A, Duranteau J. Pathophysiology of sepsis-induced acute kidney injury: the role of global renal blood flow and renal vascular resistance. Contrib Nephrol. 2011; 174:89-97.
• [4]Stoyanoff TR, Todaro JS, Aguirre MV, Zimmermann MC, Brandan NC. Amelioration of lipopolysaccharide-induced acute kidney injury by erythropoietin: involvement of mitochondria-regulated apoptosis. Toxicology. 2014; 318:13-21.
• [5]Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med. 2004; 351(2):159-169.
• [6]Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ, Gokden N et al.. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury. Am J Pathol. 2012; 180(2):505-516.
• [7]Xu C, Chang A, Hack BK, Eadon MT, Alper SL, Cunningham PN. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis. Kidney Int. 2014; 85(1):72-81.
• [8]Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest. 2009; 119(10):2868-2878.
• [9]Katsumi H, Fukui K, Sato K, Maruyama S, Yamashita S, Mizumoto E et al.. Pharmacokinetics and preventive effects of platinum nanoparticles as reactive oxygen species scavengers on hepatic ischemia/reperfusion injury in mice. Metallomics Integr Biometal Sci. 2014; 6(5):1050-1056.
• [10]Yang X, Jin L, Yao L, Shen FH, Shimer AL, Li X. Antioxidative nanofullerol prevents intervertebral disk degeneration. Int J Nanomed. 2014; 9:2419-2430.
• [11]Chistyakov VA, Smirnova YO, Prazdnova EV, Soldatov AV. Possible mechanisms of fullerene C(6)(0) antioxidant action. BioMed Res Int. 2013; 2013:821498.
• [12]Chen S, Hou Y, Cheng G, Zhang C, Wang S, Zhang J. Cerium oxide nanoparticles protect endothelial cells from apoptosis induced by oxidative stress. Biol Trace Elem Res. 2013; 154(1):156-166.
• [13]Kolli MB, Manne ND, Para R, Nalabotu SK, Nandyala G, Shokuhfar T et al.. Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension. Biomaterials. 2014; 35(37):9951-9962.
• [14]Kyosseva SV, Chen L, Seal S, McGinnis JF. Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice. Exp Eye Res. 2013; 116:63-74.
• [15]Chaudhury K, Babu KN, Singh AK, Das S, Kumar A, Seal S. Mitigation of endometriosis using regenerative cerium oxide nanoparticles. Nanomed Nanotechnol Biol Med. 2013; 9(3):439-448.
• [16]Lee SS, Song W, Cho M, Puppala HL, Nguyen P, Zhu H et al.. Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating. ACS Nano. 2013; 7(11):9693-9703.
• [17]Clark A, Zhu A, Sun K, Petty HR. Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis. J Nanoparticle Res Interdiscipl Forum Nanoscale Sci Technol. 2011; 13(10):5547-5555.
• [18]Pirmohamed T, Dowding JM, Singh S, Wasserman B, Heckert E, Karakoti AS et al.. Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun. 2010; 46(16):2736-2738.
• [19]Pourkhalili N, Hosseini A, Nili-Ahmadabadi A, Hassani S, Pakzad M, Baeeri M et al.. Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J Diabetes. 2011; 2(11):204-210.
• [20]Hosseini A, Baeeri M, Rahimifard M, Navaei-Nigjeh M, Mohammadirad A, Pourkhalili N et al.. Antiapoptotic effects of cerium oxide and yttrium oxide nanoparticles in isolated rat pancreatic islets. Hum Exp Toxicol. 2013; 32(5):544-553.
• [21]Gao Y, Chen K, Ma JL, Gao F. Cerium oxide nanoparticles in cancer. OncoTargets Therapy. 2014; 7:835-840.
• [22]Alili L, Sack M, von Montfort C, Giri S, Das S, Carroll KS et al.. Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid Redox Signal. 2013; 19(8):765-778.
• [23]Estevez AY, Pritchard S, Harper K, Aston JW, Lynch A, Lucky JJ et al.. Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radic Biol Med. 2011; 51(6):1155-1163.
• [24]Manne ND, Arvapalli R, Nepal N, Thulluri S, Selvaraj V, Shokuhfar T et al.. Therapeutic potential of cerium oxide nanoparticles for the treatment of peritonitis induced by polymicrobial insult in Sprague–Dawley rats. Crit Care Med. 2015.
• [25]Pinto CF, Watanabe M, da Fonseca CD, Ogata CI, Vattimo Mde F. The sepsis as cause of acute kidney injury: an experimental model. Revista da Escola de Enfermagem da U S P. 2012;46: 86–90.
• [26]Wu L, Gokden N, Mayeux PR. Evidence for the role of reactive nitrogen species in polymicrobial sepsis-induced renal peritubular capillary dysfunction and tubular injury. J Am Soc Nephrol JASN. 2007; 18(6):1807-1815.
• [27]Sack M, Alili L, Karaman E, Das S, Gupta A, Seal S et al.. Combination of conventional chemotherapeutics with redox-active cerium oxide nanoparticles-a novel aspect in cancer therapy. Mol Cancer Ther. 2014.
• [28]Younce CW, Wang K, Kolattukudy PE. Hyperglycaemia-induced cardiomyocyte death is mediated via MCP-1 production and induction of a novel zinc-finger protein MCPIP. Cardiovasc Res. 2010; 87(4):665-674.
• [29]Adembri C, Sgambati E, Vitali L, Selmi V, Margheri M, Tani A et al.. Sepsis induces albuminuria and alterations in the glomerular filtration barrier: a morphofunctional study in the rat. Crit Care. 2011; 15(6):R277. BioMed Central Full Text
• [30]Park SW, Chen SW, Kim M, D’Agati VD, Lee HT. Human heat shock protein 27-overexpressing mice are protected against acute kidney injury after hepatic ischemia and reperfusion. Am J Physiol Renal Physiol. 2009; 297(4):F885-F894.
• [31]Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013; 34(3):129-136.
• [32]Hirst SM, Karakoti A, Singh S, Self W, Tyler R, Seal S et al.. Bio-distribution and in vivo antioxidant effects of cerium oxide nanoparticles in mice. Environ Toxicol. 2013; 28(2):107-118.
• [33]Yang N, Luo M, Li R, Huang Y, Zhang R, Wu Q et al.. Blockage of JAK/STAT signalling attenuates renal ischaemia-reperfusion injury in rat. Nephrol Dial Transplant Off Publ Eur Dial Transplant Assoc Eur Renal Assoc. 2008; 23(1):91-100.
• [34]Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci. 2004; 117(Pt 8):1281-1283.
• [35]Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56(4):549-580.
• [36]Kockara A, Kayatas M. Renal cell apoptosis and new treatment options in sepsis-induced acute kidney injury. Ren Fail. 2013; 35(2):291-294.
• [37]Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K et al.. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science. 1997; 278(5336):294-298.
• [38]Doi K, Yuen PS, Eisner C, Hu X, Leelahavanichkul A, Schnermann J et al.. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol JASN. 2009; 20(6):1217-1221.
• [39]Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008; 48:463-493.
• [40]Zhang Z. Biomarkers, diagnosis and management of sepsis-induced acute kidney injury: a narrative review. Heart Lung Vessels. 2015; 7(1):64-73.
• [41]Hannon RJ, Boston VE. Hyponatraemia and intracellular water in sepsis: an experimental comparison of the effect of fluid replacement with either 0.9 % saline or 5 % dextrose. J Pediatr Surg. 1990; 25(4):422-425.
• [42]Chopra M, Golden HB, Mullapudi S, Dowhan W, Dostal DE, Sharma AC. Modulation of myocardial mitochondrial mechanisms during severe polymicrobial sepsis in the rat. PLoS One. 2011; 6(6):e21285.
• [43]Wang C, Blough ER, Arvapalli R, Dai X, Paturi S, Manne N et al.. Metabolic syndrome-induced tubulointerstitial injury: role of oxidative stress and preventive effects of acetaminophen. Free Radic Biol Med. 2013; 65:1417-1426.
• [44]Manne ND, Lima M, Enos RT, Wehner P, Carson JA, Blough E. Altered cardiac muscle mTOR regulation during the progression of cancer cachexia in the ApcMin/+mouse. Int J Oncol. 2013; 42(6):2134-2140.