Gadolinium Orthovanadate GdVO4:Eu3+ Nanoparticles Ameliorate Carrageenan-Induced Intestinal Inflammation

Anton Tkachenko; Denys Pogozhykh; Anatolii Onishchenko; Valeriy Myasoedov; Leonid Podrigalo; Vladimir Klochkov; Tetyana Chumachenko; Volodymyr Prokopyuk; Svetlana Yefimova; Galina Gubina-Vakulyck; Nataliya Kavok; Dmytro Butov; Andrii Andrieiev; Hanna Polikarpova; Oksana Nakonechna

doi:10.29169/1927-5951.2021.11.06

Gadolinium Orthovanadate GdVO4:Eu3+ Nanoparticles Ameliorate Carrageenan-Induced Intestinal Inflammation

Authors

Anton Tkachenko Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Trinklera st. 6, 61022 Kharkiv, Ukraine
Denys Pogozhykh Clinic for Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
Anatolii Onishchenko Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Trinklera st. 6, 61022 Kharkiv, Ukraine
Valeriy Myasoedov Department of Medical Biology, Kharkiv National Medical University, Nauky ave. 4, 61022, Kharkiv, Ukraine
Leonid Podrigalo Department of Medical Science, Kharkiv State Academy of Physical Culture, Klochkovska str., 99, 61022, Ukraine
Vladimir Klochkov Yu.V. Malyukin Department of Nanostructured Materials, Institute for Scintillation Materials National Academy of Sciences of Ukraine, Nauky ave. 60, 61072 Kharkiv, Ukraine
Tetyana Chumachenko Department of Epidemiology, Kharkiv National Medical University, Trinklera st. 12, 61022 Kharkiv, Ukraine
Volodymyr Prokopyuk Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Trinklera st. 6, 61022 Kharkiv, Ukraine
Svetlana Yefimova Yu.V. Malyukin Department of Nanostructured Materials, Institute for Scintillation Materials National Academy of Sciences of Ukraine, Nauky ave. 60, 61072 Kharkiv, Ukraine
Galina Gubina-Vakulyck Department of Pathological Anatomy, Kharkiv National Medical University, Nauky ave. 4, 61022 Kharkiv, Ukraine
Nataliya Kavok Yu.V. Malyukin Department of Nanostructured Materials, Institute for Scintillation Materials National Academy of Sciences of Ukraine, Nauky ave. 60, 61072 Kharkiv, Ukraine
Dmytro Butov Department of Phthisiology and Pulmonology, Kharkiv National Medical University, Newton st. 145, 61000 Kharkiv, Ukraine
Andrii Andrieiev Department of Pathological Anatomy, Kharkiv National Medical University, Nauky ave. 4, 61022 Kharkiv, Ukraine
Hanna Polikarpova Department of Biochemistry, Kharkiv National Medical University, Nauky ave. 4, 61022 Kharkiv, Ukraine
Oksana Nakonechna Department of Biochemistry, Kharkiv National Medical University, Nauky ave. 4, 61022 Kharkiv, Ukraine

DOI:

https://doi.org/10.29169/1927-5951.2021.11.06

Keywords:

Carrageenan, food additive E407a, flow cytometry, apoptosis, necrosis, nanoparticles

Abstract

Gadolinium orthovanadate GdVO₄:Eu³⁺ nanoparticles (VNPs) have been shown to scavenge reactive oxygen species (ROS), making them a promising therapeutic agent in inflammation.

This study aims to assess the effects of VNPs administered orally on E407a-induced inflammation.

Materials and Methods: Fragments of the small intestine of 8 rats treated orally with a carrageenan-containing food additive E407a at a dose of 140 mg / kg of weight during 2 weeks, 8 animals orally exposed to both E407a and VNPs at a dose of 20 μg / kg of weight during the same period of time, and 8 control rats were stained routinely and immunostained for CD3 and CD68 with the subsequent immunohistochemical scoring. Moreover, analysis of viability and cell death modes of granulocytes was performed by flow cytometry using Annexin V and 7-aminoactinomycin D (7-AAD).

Results: Oral exposure to the food additive E407a resulted in the development of enteritis associated with altered small intestinal morphology, infiltration of the lamina propria with macrophages and T-lymphocytes, and activation of peripheral blood granulocyte apoptosis. VNPs administered against the background of E407a-induced slight intestinal inflammation improved small intestinal morphology, decreased infiltration rate of the immune cells mentioned above without affecting the intensity of granulocyte apoptosis.

Conclusion: Oral administration of VNPs ameliorates E407a-induced enteritis.

References

Gupta R, Xie H. Nanoparticles in daily life: applications, toxicity and regulations. J Environ Pathol Toxicol Oncol 2018; 37(3): 209-230. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2018026009 DOI: https://doi.org/10.1615/JEnvironPatholToxicolOncol.2018026009

Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arabian Journal of Chemistry 2019; 12(7): 908-931.https://doi.org/10.1016/j.arabjc.2017.05.011 DOI: https://doi.org/10.1016/j.arabjc.2017.05.011

Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein J Nanotechnol 2018; 9: 1050-1074. https://doi.org/10.3762/bjnano.9.98 DOI: https://doi.org/10.3762/bjnano.9.98

Anselmo AC, Mitragotri S. Nanoparticles in the clinic: an update. Bioeng Transl Med 2019; 4(3): e10143. https://doi.org/10.1002/btm2.10143 DOI: https://doi.org/10.1002/btm2.10143

Anselmo AC, Mitragotri S. Nanoparticles in the clinic. Bioeng Transl Med 2016; 1(1): 10-29. https://doi.org/10.1002/btm2.10003 DOI: https://doi.org/10.1002/btm2.10003

Giner-Casares JJ, Henriksen-Lacey M, Coronado-Puchau M, Liz-Marzán LM. Inorganic nanoparticles for biomedicine: where materials scientists meet medical research. Materials Today 2016; 19(1): 19-28. https://doi.org/10.1016/j.mattod.2015.07.004 DOI: https://doi.org/10.1016/j.mattod.2015.07.004

Awasthi R, Roseblade A, Hansbro PM, Rathbone MJ, Dua K, Bebawy M. Nanoparticles in cancer treatment: Opportunities and obstacles. Curr Drug Targets 2018; 19(14): 1696-1709. https://doi.org/10.2174/1389450119666180326122831 DOI: https://doi.org/10.2174/1389450119666180326122831

Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future. Int J Nanomedicine 2017; 12: 1227-1249. https://doi.org/10.2147/IJN.S121956 DOI: https://doi.org/10.2147/IJN.S121956

AgarwalH, Nakara A, Shanmugam VK. Anti-inflammatory mechanism of various metal and metal oxide nanoparticles synthesized using plant extracts: A review. Biomedicine & Pharmacotherapy 2019; 109: 2561-2572. https://doi.org/10.1016/j.biopha.2018.11.116 DOI: https://doi.org/10.1016/j.biopha.2018.11.116

Poupot R, Bergozza D, Fruchon S. Nanoparticle-based strategies to treat neuro-inflammation. Materials (Basel) 2018; 11(2): 270. https://doi.org/10.3390/ma11020270 DOI: https://doi.org/10.3390/ma11020270

Katsuki S, Matoba T, Koga JI, Nakano K, Egashira K. Anti-inflammatory nanomedicine for cardiovascular disease. Front Cardiovasc Med 2017; 4: 87. https://doi.org/10.3389/fcvm.2017.00087 DOI: https://doi.org/10.3389/fcvm.2017.00087

Khurana A, Tekula S, Saifi MA, Venkatesh P, Godugu C. Therapeutic applications of selenium nanoparticles. Biomed Pharmacother 2019; 111: 802-812. https://doi.org/10.1016/j.biopha.2018.12.146 DOI: https://doi.org/10.1016/j.biopha.2018.12.146

Casals E, Gusta MF, Piella J, Casals G, Jiménez W, Puntes V. Intrinsic and extrinsic properties affecting innate immune responses to nanoparticles: The case of cerium oxide. Front Immunol 2017; 8: 970. https://doi.org/10.3389/fimmu.2017.00970 DOI: https://doi.org/10.3389/fimmu.2017.00970

Averchenko EA, Kavok NS, Klochkov VK, Malyukin YuV. Chemiluminescent diagnostics of free-radical processes in an abiotic system and in liver cells in the presence of nanoparticles based on rare-earth elements nReVO4: Eu3+(Re = Gd, Y, La) and CeO2. J Appl Spectrosc 2014; 81: 827-833.https://doi.org/10.1007/s10812-014-0012-9 DOI: https://doi.org/10.1007/s10812-014-0012-9

Nikitchenko YV, Klochkov VK. Kavok NS, Karpenko NA, Sedyh OO, Bozhkov AI, et al. Gadolinium orthovanadate nanoparticles increase survival of old rats. Dopov. Nac. akad. nauk Ukr 2020; 2: 29-36

[in Russian] .https://doi.org/10.15407/dopovidi2020.02.029 DOI: https://doi.org/10.15407/dopovidi2020.02.029

Sun H, Jiang C, Wu L, Bai X, Zhai S. Cytotoxicity-related bioeffects induced by nanoparticles: the role of surface chemistry. Front Bioeng Biotechnol 2019; 7: 414. https://doi.org/10.3389/fbioe.2019.00414 DOI: https://doi.org/10.3389/fbioe.2019.00414

De Matteis V. Exposure to inorganic nanoparticles: routes of entry, immune response, biodistribution and in vitro/in vivotoxicity evaluation. Toxics 2017; 5(4): 29. https://doi.org/10.3390/toxics5040029 DOI: https://doi.org/10.3390/toxics5040029

Khalili Fard J, Jafari S, Eghbal MA. A review of molecular mechanisms involved in toxicity of nanoparticles. Adv Pharm Bull 2015; 5(4): 447-454. https://doi.org/10.15171/apb.2015.061 DOI: https://doi.org/10.15171/apb.2015.061

Sabella S, Carney RP, Brunetti V, Malvindi MA, Al-Juffali N, Vecchio G, et al. A general mechanism for intracellular toxicity of metal-containing nanoparticles. Nanoscale 2014; 6(12): 7052-61. https://doi.org/10.1039/c4nr01234h DOI: https://doi.org/10.1039/c4nr01234h

Tkachenko AS, Klochkov VK, LesovoyVN, Myasoedov VV, KavokNS, OnishchenkoAS, et al. Orally administered gadolinium orthovanadate GdVO4: Eu3+ nanoparticles don’t affect the hydrophobic region of cell membranes of leukocytes. Wien. Med. Wochenschr 2020; 170(7): 189-195. https://doi.org/10.1007/s10354-020-00735-4 DOI: https://doi.org/10.1007/s10354-020-00735-4

Klochkov VK, Malyshenko AI, Sedyh OO, Malyukin YuV. Wet-chemical synthesis and characterization of luminescent colloidal nanoparticles: ReVO4: Eu3+ (Re=La, Gd, Y) with rod-like and spindle-like shape. Functional materials 2011; 1: 111-115.

Eiró N, Pidal I, Fernandez-Garcia B, Junquera S, Lamelas ML, del Casar JM, et al. Impact of CD68/(CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer. PLoS One 2012; 7(12): e52796.https://doi.org/10.1371/journal.pone.0052796 DOI: https://doi.org/10.1371/journal.pone.0052796

Sjödahl G, Lövgren K, Lauss M, Chebil G, Patschan O, Gudjonsson S, et al. Infiltration of CD3⁺ and CD68⁺ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors. Urol Oncol 2014; 32 (6): 791-7. https://doi.org/10.1016/j.urolonc.2014.02.007 DOI: https://doi.org/10.1016/S1569-9056(14)60778-8

Areshidze D, Timchenko L, Rzhepakovsky I, Kozlova MA, Kuznetsova IA, Makartseva LA. Anti-inflammatory effect of nicavet-2500 in rodent models of acute inflammation. Journal of Pharmacy and Nutrition Sciences 2018; 8(2): 35-41.https://doi.org/10.6000/1927-5951.2018.08.02.2 DOI: https://doi.org/10.6000/1927-5951.2018.08.02.2

Shaza Anwar Al Laham. Histopathological changes of the effect of ketotifen in a rat model of nephropathy. Journal of Pharmacy and Nutrition Sciences 2019; 9(2): 130-135. https://doi.org/10.29169/1927-5951.2019.09.02.13 DOI: https://doi.org/10.29169/1927-5951.2019.09.02.13

Tkachenko AS, Onishchenko AI,LesovoyVN, Myasoedov VV. Common food additive E407a affects BCL-2 expression in lymphocytes in vitro.Studia Univ. VG, SSV 2019; 29(4): 169-76.

David S, Shani Levi C, Fahoum L, Ungar Y, Meyron-Holtz EG, Shpigelman A, et al. Revisiting the carrageenan controversy: do we really understand the digestive fate and safety of carrageenan in our foods? Food Funct 2018; 9(3): 1344-1352.https://doi.org/10.1039/C7FO01721A DOI: https://doi.org/10.1039/C7FO01721A

Tkachenko A, Marakushyn D, Kalashnyk I, Korniyenko Y, Onishchenko A, Gorbach T, et al. A study of enterocyte membranes during activation of apoptotic processes in chronic carrageenan-induced gastroenterocolitis. Med Glas (Zenica) 2018; 15(2): 87-92.

McKim JM Jr, Baas H, Rice GP, Willoughby JA Sr, Weiner ML, Blakemore W. Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines. Food Chem Toxicol 2016; 96: 1-10. https://doi.org/10.1016/j.fct.2016.07.006 DOI: https://doi.org/10.1016/j.fct.2016.07.006

Gubina-Vakyulyk GI, Gorbach TV, Tkachenko AS, Tkachenko MO. Damage and regeneration of small intestinal enterocytes under the influence of carrageenan induces chronic enteritis. Comparative Clinical Pathology 2015; 24(6): 1473-1477. https://doi.org/10.1007/s00580-015-2102-3 DOI: https://doi.org/10.1007/s00580-015-2102-3

Necas J, Bartosikova L. Carrageenan: a review. Veterinarni Medicina 2013; 58: 187-205.https://doi.org/10.17221/6758-VETMED DOI: https://doi.org/10.17221/6758-VETMED

Bhattacharyya S, Dudeja PK, Tobacman JK. Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10. Biochimica et Biophysica Acta—General Subjects 2008; 1780(7-8): 973-982. https://doi.org/10.1016/j.bbagen.2008.03.01 DOI: https://doi.org/10.1016/j.bbagen.2008.03.019