1. bookVolume 1 (2017): Issue 1 (January 2017)
Journal Details
License
Format
Journal
eISSN
2564-615X
First Published
30 Jan 2017
Publication timeframe
4 times per year
Languages
English
access type Open Access

Biological effects induced by Gadolinium nanoparticles on Lymphocyte A20 cell line

Published Online: 27 Jan 2017
Volume & Issue: Volume 1 (2017) - Issue 1 (January 2017)
Page range: 57 - 64
Received: 27 Jan 2017
Journal Details
License
Format
Journal
eISSN
2564-615X
First Published
30 Jan 2017
Publication timeframe
4 times per year
Languages
English
Abstract

Gadolinium nanoparticles (GdNPs) are potential agents for MRI of lymph nodes. The aim of this study was to evaluate the in vitro effects of 1 μM, 2.5 μM and 5 μM of GdDOTA⊂CS-TPP/HA and GdDOTP⊂CS-TPP/HA NPs on A20 lymphocyte cells exposed for 6 and 24 hours. The total cellular biomass (SRB), lactate dehydrogenase activity (LDH) and oxidative stress parameters, such as reactive oxygen species generation (ROS), reduced glutathione (GSH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were analyzed by spectrophotometric and fluorimetric methods. After cells exposure to 1 μM, 2.5 μM and 5 μM of GdDOTP⊂CS-TPP/HA NPs their viability decreased in a time- and dose-dependent manner, whereas for GdDOTA⊂CS-TPP/HA no significant changes were noticed. Both NPs formulations in doses of 1 μM, 2.5 μM, 5 μM did not affect the plasma membrane at each time point tested. The levels of ROS, MDA and AOPP increased proportionally with the concentration and exposure time. GSH concentration decreased significantly for all doses of both NPs tested. Taken together our data suggest that, GdDOTP⊂CS-TPP/HA and GdDOTA⊂CS-TPP/HA NPs induced oxidative stress in A20 lymphocyte cells which was counteracted by the cells antioxidant defense system to a certain extend.

1. Delli Castelli D, Gianolio E, Geninatti Crich S, Terreno E, Aime S. Metal containing nanosized systems for MR-Molecular Imaging applications. Coordin Chem Rev 2008; 252(21-22): 2424-2443.10.1016/j.ccr.2008.05.006Search in Google Scholar

2. Merbach AS, Helm L, Toth E. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging, 2013, Wiley and Sons, Chichester, 2nd Edn.10.1002/9781118503652Search in Google Scholar

3. Geraldes CFGC, Laurent S. Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media Mol I 2009; 4(1): 1-23.10.1002/cmmi.26519156706Open DOISearch in Google Scholar

4. Idee JM, Port M, Medina C, Lancelot E, Fayoux E, Ballet S, Corot C. Possible involvement of gadolinium chelates in the pathophysiology of nephrogenic systemic fibrosis: a critical review. Toxicology 2008; 248(2-3): 77-88.10.1016/j.tox.2008.03.01218440117Search in Google Scholar

5. Rogosnitzky M, Branch S. Gadolinium-based contrast agent toxicity: a rewiew of known and proposed mechanisms. Biometals 2016; 29: 365-376.10.1007/s10534-016-9931-7487915727053146Open DOISearch in Google Scholar

6. Courant T, Roullin VG, Cadiou C, Callewaert M, Andry MC, Portefaix C, Hoeffel C, de Goltstein MC, Port M, Laurent S, Vander Elst L, Muller R, Molinari M, Chuburu F. Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast agents Angew Chem Int Edit 2012; 51: 9119-9122.10.1002/anie.20120319022865621Open DOISearch in Google Scholar

7. Callewaert M, Roullin VG, Cadiou C, Millart E, Van Gulik L, Andry MC, Portefaix C, Hoeffel C, Laurent S, Vander Elst L, Muller R, Molinari M, Chuburu F. Tuning the composition of biocompatible Gd nanohydrogels to achieve hypersensitive dual T1/T2 MRI contrast agents. J Mater Chem B 2014; 2: 6397-6405.10.1039/C4TB00783B32262156Open DOISearch in Google Scholar

8. Fang JY, Chen JP, Leu YL, Hu JW. Temperature-sensitive hydrogels composed of chitosan and hyaluronic acid as injectable carriers for drug delivery. Eur J Pharm Biopharm 2008; 68(3): 626-636.10.1016/j.ejpb.2007.08.01217904339Search in Google Scholar

9. Oyarzun-Ampuero FA, Brea J, Loza MI, Torres D, Alonso MJ. Chitosan- hyaluronic acid nanoparticles loaded with heparin for the treatment of asthma. Int J Pharm 2009; 381(2): 122-129.10.1016/j.ijpharm.2009.04.00919467809Search in Google Scholar

10. Luo Y, Wang Q. Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. Int J Biol Macromol 2014; 64: 353-367.10.1016/j.ijbiomac.2013.12.01724360899Search in Google Scholar

11. Al-Qadi S, Alatorre-Meda M, Zaghloul EM, Taboada P, Remunan- Lopez C. Chitosan-hyaluronic acid nanoparticles for gene silencing: The role of hyaluronic acid on the nanoparticles’ formation and activity. Colloid Surface B 2013; 103: 615-623.10.1016/j.colsurfb.2012.11.009Search in Google Scholar

12. Deng X, Cao M, Zhang J, Hu K, Yin Z, Zhou Z, Xiao X, Yang Y, Sheng W, Wu Y. Hyaluronic acid-chitosan nanoparticles for co-delivery of MIR-34A and doxorubicin in therapy against triple negative breast cancer. Biomaterials 2014; 35(14): 4333-4344.10.1016/j.biomaterials.2014.02.006Search in Google Scholar

13. Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z. Polysaccharides-based nanoparticles as drug delivery systems. Adv Drug Deliver Rev 2008; 60(15): 1650-1662.10.1016/j.addr.2008.09.001Search in Google Scholar

14. Kean T, Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Deliver Rev 2010; 62(1): 3-11. 10.1016/j.addr.2009.09.004Search in Google Scholar

15. Lewinski N, Colvin V, Drezek R. Cytotoxicity of nanoparticles. Small 2008; 4(1): 26-49.10.1002/smll.200700595Open DOISearch in Google Scholar

16. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein- dye binding Anal Biochem 1976; 72: 248-254. Search in Google Scholar

17. Dinischiotu A, Stanca L, Gradinaru D, Petrache SN, Radu M, Serban A. Chapter 10, Lipid Peroxidation due to in vitro and in vivo exposure of biological samples to nanoparticles. In Oxidative Stress and Nanotechnology: Methods and Protocols, Methods in Molecular Biology 2013, Armstrong D, Bharali, DJ, Eds., Springer Science Business Media: New York, NY, USA, 1028: 155-164.Search in Google Scholar

18. Wan CP, Myung E, Lau BH. An automated microfluorometric assay for monitoring oxidative burst activity of phagocytes. J Immunol Methods 1993; 159(1-2): 131-138.10.1016/0022-1759(93)90150-6Search in Google Scholar

19. Witko-Sarsat V, Nguyen AT, Descamps-Latscha B. Microtiter plate assay for phagocyte-derived taurine-chloramines. J Clin Lab Anal 1992; 6(1): 47-53.10.1002/jcla.18600601101542083Open DOISearch in Google Scholar

20. Greenberg SA. Zinc transmetallation and gadolinium retention after MR imaging: case report. Radiology 2010; 257(3): 670-673.10.1148/radiol.1010056020829541Search in Google Scholar

21. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, Thomsen HS. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance Imaging. J Am Soc Nephrol 2006; 17: 2359-2362.10.1681/ASN.200606060116885403Open DOISearch in Google Scholar

22. Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging 2009; 30(6): 1259-1267.10.1002/jmri.21969282246319938038Open DOISearch in Google Scholar

23. Xia D, Davis RL, Crawford JA, Abraham JL. Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy. Acta Radiol 2010; 51(10): 1126-1136.10.3109/02841851.2010.51561420868305Search in Google Scholar

24. Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE. Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics 2009; 1(6): 479-488.10.1039/b905145g21305156Search in Google Scholar

25. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release 2004; 100(1): 5-28.10.1016/j.jconrel.2004.08.01015491807Search in Google Scholar

26. Yan GP, Xu W, Yang L, Li L, Liu F, Guo QZ. Dextran gadolinium complexes as contrast agents for magnetic resonance imaging to sentinel lymph nodes. Pharm Res 2010; 27(9): 1884-1892.10.1007/s11095-010-0187-620559699Open DOISearch in Google Scholar

27. Darras V, Nelea M, Winnik FM, Buschmann MD. Chitosan modified with gadolinium diethylenetriaminepentaacetic acid for magnetic resonance imaging of DNA/chitosan nanoparticles. Carbohyd Polym 2010; 80(4): 1137-1146.10.1016/j.carbpol.2010.01.035Open DOISearch in Google Scholar

28. Chen Z, Yu D, Liu C, Yang X, Zhang N, Ma C, Song J, Lu Z. Gadolinium- conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent. J Drug Target 2011; 19(8): 657-665.10.3109/1061186X.2010.53172721091273Search in Google Scholar

29. Ge Y, Zhang Y, He S, Nie F, Teng G, Gu N. Fluorescence modified chitosan coated magnetic nanoparticles for high-efficient cellular imaging. Nanoscale Res Lett 2009; 4: 287-295.10.1007/s11671-008-9239-9289343720596545Search in Google Scholar

30. Donnou S, Galand C, Touitou V, Sautes-Fridman C, Fabry Z, Fisson S. Murine Models of B-Cell Lymphomas: Promising Tools for Designing Cancer Therapies. Adv Hematol 2012; 1-13.10.1155/2012/701704328702222400032Search in Google Scholar

31. Palmieri C, Falcone C, Iaccino E, Tuccillo FM, Gaspari M, Trimboli F, De Laurentiis A, Luberto L, Pontoriero M, Pisano A, Vecchio E, Fierro O, Panico MR, Larobina M, Gargiulo S, Costa N, Dal Piaz F, Schiavone M, Arra C, Giudice A, Palma G, Barbieri A, Quinto I, Scala G. In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder. Blood 2010; 116(2): 226-238.10.1182/blood-2009-11-25361720363775Search in Google Scholar

32. Chaise C, Itti E, Petegnief Y, Wirquin E, Copie-Bergman C, Farcet JP, Delfau-Larue MH, Meignan M, Talbot JN, Molinier-Frenkel V. (F-18)-Fluoro-2-deoxy-D-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murineSearch in Google Scholar

B cell lymphoma model. Cancer Immunol Immun 2007; 56: 1163-1171. 10.1007/s00262-006-0265-0191940017171356Search in Google Scholar

33. Siegel S, Wagner A, Schmitz N, Zeis M. Induction of antitumour immunity using survivin peptide-pulsed dendritic cells in a murine lymphoma model. Brit J Haematol 2003; 122: 911-914.10.1046/j.1365-2141.2003.04535.x12956760Search in Google Scholar

34. Buzea C, Pacheco Blandino II, Robbie K. Nanomaterials and nanoparticles:Sources and toxicity. Biointerphases 2007; 2(4): MR17 - MR172.10.1116/1.281569020419892Search in Google Scholar

35. Avti PK, Caparelli ED, Sitharaman B. Cytotoxicity, cytocompatibility, cell-labeling efficiency, and in vitro cellular magnetic resonance imaging of gadolinium-catalyzed single-walled carbon nanotubes. J Biomed Mater Res A 2013; 101A(12): 3580-3591.10.1002/jbm.a.34643378556223686792Search in Google Scholar

36. Heinrich MC, Kuhlmann MK, Kohlbacher S, Scheer M, Grgic A, Heckmann MB, Uder M. Cytotoxicity of Iodinated and Gadolinium- based Contrast Agents in Renal Tubular Cells at Angiographic Concentrations:In Vitro Study. Radiology 2007; 242(2): 425-434.10.1148/radiol.242206024517179401Search in Google Scholar

37. Do C, Barnes JL, Tan C, Wagner B. Type of MRI contrast, tissue gadolinium, and fibrosis. Am J Physiol-Renal 2014; 307: F844-F855. 10.1152/ajprenal.00379.2014425023125100280Search in Google Scholar

38. Liu Y, Chen Z, Liu C, Yu D, Lu Z, Zhang N. Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. Biomaterials 2011; 32(22): 5167-5176.10.1016/j.biomaterials.2011.03.07721521627Open DOISearch in Google Scholar

39. Zhang L, Liu Y, Yu D, Zhang N. Gadolinium-Loaded Chitosan Nanoparticles as Magnetic Resonance Imaging Contrast Agents for the Diagnosis of Tumor. J Biomed Nanotechnol 2013; 9: 863-869.10.1166/jbn.2013.158423802417Search in Google Scholar

40. Zhang L, Liu T, Xiao Y, Yu D, Zhang N. Hyaluronic Acid-Chitosan Nanoparticles to Deliver Gd-DTPA for MR Cancer Imaging. Nanomaterials 2015; 5(3): 1379-1396.10.3390/nano5031379530462928347070Search in Google Scholar

41. Feng X, Xia Q, Yuan L, Yang X, Wang K. Impaired mitochondrial function and oxidative stress in rat cortical neurons: Implications for gadolinium-induced neurotoxicity. Neurotoxicology 2010; 31: 391-398.10.1016/j.neuro.2010.04.00320398695Open DOISearch in Google Scholar

42. Xia Q, Feng XD, Yuan L, Wang K, Yang XD. Brain-derived neurotrophic factor protects neurons from GdCl3-induced impairment in neuron-astrocyte co-cultures. Sci China Chem 2010; 53(10): 2193-2199.10.1007/s11426-010-4105-xSearch in Google Scholar

43. Xia Q, Feng X, Huang H, Du L, Yang X, Wang K. Gadolinium-induced oxidative stress triggers endoplasmic reticulum stress in rat cortical neurons. J Neurochem 2011; 117(1): 38-47.10.1111/j.1471-4159.2010.07162.xSearch in Google Scholar

44. Kumari A, Yadav SK. Cellular interactions of therapeutically delivered nanoparticles. Expert Opin Drug Del 2011; 8(2): 141-151. 10.1517/17425247.2011.547934Open DOISearch in Google Scholar

45. Rima W, Sancey L, Aloy MT, Armandy E, Alcantara GB, Epicier T, Malchere A, Joly-Pottuz L, Mowat P, Lux F, Tillement O, Burdin B, Rivoire A, Boule C, Anselme-Bertrand I, Pourchez J, Cottier M, Roux S, Rodriguez-Lafrasse C, Perriat P. Internalization pathways into cancer cells of gadolinium-based radiosensitizing Boanoparticles. Biomaterials 2013; 34: 181-195.10.1016/j.biomaterials.2012.09.029Open DOISearch in Google Scholar

46. Štefančikova L, Porcel E, Eustache P, Li S, Salado D, Marco S, Guerquin- Kern JL, Refregiers M, Tillement O, Lux F, Lacombe S. Cell localisation of gadolinium-based nanoparticles and related radiosensitising efficacy in glioblastoma cells. Cancer Nanotechnology 2014; 5(6): 1-15.10.1186/s12645-014-0006-6Search in Google Scholar

47. Oyewumi MO, Yokel RA, Jay M, Coakley T, Mumper RJ. Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice. J Control Release 2004; 95: 613- 626.10.1016/j.jconrel.2004.01.002Search in Google Scholar

48. Dodane V, Vilivalam VD. Pharmaceutical applications of chitosan. Pharm Sci Technol To 1998; 1: 246-253.10.1016/S1461-5347(98)00059-5Search in Google Scholar

49. Bose C, Megyesi JK, Shah SV, Hiatt KM, Hall KA, Karaduta O, Swaminathan S. Evidence suggesting a role of iron in a mouse model of nephrogenic systemic fibrosis. PLoS ONE 2015; 10(8): e0136563.10.1371/journal.pone.0136563454921426305890Search in Google Scholar

50. Chen R, Ling D, Zhao L, Wang S, Liu Y, Bai R, Baik S, Zhao Y, Chen C, Hyeon T. Parallel comparative studies on mouse toxicity of oxide nanoparticle- and gadolinium-based T1 MRI contrast agents. ACS Nano 2015; 9(12): 12425-12435.10.1021/acsnano.5b0578326567968Search in Google Scholar

51. Idee JM, Fretellier N, Robic C, Corot C. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update. Crit Rev Toxicol 2014; 44: 895-913.10.3109/10408444.2014.95556825257840Search in Google Scholar

52. Pereira LVB, Shimizu MHM, Rodrigues LPMR, Leite CC, Andrade L, Seguro AC. N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity. PLoS ONE 2012; 7(7): e39528.10.1371/journal.pone.0039528339798722815709Search in Google Scholar

53. Ramalho J, Semelka RC, Ramalho M, Nunes RH, AlObaidy M, Castillo M. Gadolinium-based contrast agent accumulation and toxicity: an update. Am J Neuroradiol 2015; 1-7.10.3174/ajnr.A4615Search in Google Scholar

54. Repetto M, Semprine J, Boveris A. Lipid Peroxidation: Chemical Mechanism, Biological Implications and Analytical Determination. InTech 2012, Chapter 1, 3-31.10.5772/45943Search in Google Scholar

55. Hasegawa M, Yagi K, Iwakawa S, Hirai M. Chitosan Induces Apoptosis via Caspase-3 Activation in Bladder Tumor Cells. Jpn J Cancer Res 2001; 92: 459-466.10.1111/j.1349-7006.2001.tb01116.xOpen DOISearch in Google Scholar

56. Sies H. Glutathione and its role in cellular functions. Free Radical Bio Med 1999; 27(9/10): 916-921.10.1016/S0891-5849(99)00177-XSearch in Google Scholar

57. Pastore A, Federici G, Bertini E, Piemonte F. Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 2003; 333(1): 19-39.10.1016/S0009-8981(03)00200-6Search in Google Scholar

58. Perez OD, Nolan GP, Magda D, Miller RA, Herzenberg LA. Motexafin gadolinium (Gd-Tex) selectively induces apoptosis in HIV-1 infected CD4+ T helper cells. Proc Natl Acad Sci U S A 2002; 99(4): 2270-2274.10.1073/pnas.26171149912235411854523Search in Google Scholar

59. Capeillere-Blandin C, Gausson V, Descamps-Latscha B, Witko-Sarsat V. Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim Biophys Acta 2004; 1689: 91-102.10.1016/j.bbadis.2004.02.00815196590Search in Google Scholar

60. Witko-Sarsat V, Gausson V, Nguyen AT, Touam M, Drueke T, Santangelo F, Descamps-Latscha B. AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target for N-acetylcysteine treatment in dialysis patients. Kidney Int 2003; 64: 82-91.10.1046/j.1523-1755.2003.00044.x12787398Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo