Document Type : Original Article

Authors

1 Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran

2 Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran, Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran, Department of Oncology‑Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska, Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden

3 Department of Biotechnology , School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

4 Department of Pathobiology and Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

5 Department of Immunology, School of Medicine, Iranian Blood Transfusion Research Center, Tarbiat Modares University, Tehran, Iran

Abstract

BACKGROUND: Transfusion of healthy red blood cells (RBCs) after storage is important. One of
the storage lesions on blood bags is oxidative stress. One way to prevent increased oxidative stress
is to use antioxidant nanoparticles (NPs). Superoxide dismutase (SOD) and catalase (CAT) play
an important role in antioxidant defense on RBC. poly lactic-co-glycolic acid (PLGA) is a nontoxic
biodegradable polymer that is approved by the Food and Drug Administration for drug delivery. This
study aimed to assess dose-dependent efficacy of SOD-CAT-polyethylene glycol -PLGA on RBCs
storage.
MATERIALS AND METHODS: Using a descriptive study, during 1 month, twenty donors from
Bojnourd Blood Donation Center were selected. NPs with different concentrations were injected
into the satellite bags after directing blood to them. On target days, experiments were performed on
the samples taken. Electrospray was employed to prepare SOD-CAT-PLGA NPs. Twenty packed
RBCs were isolated from the whole blood bags by the mechanical method, and certain amount of
product was transferred to the satellite bags. On days 1, 7, 14, 21, 28, and 35, bags were sampled.
Malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), and Annexin V were performed on
the samples taken. The repeated measures analysis with the help of SPSS software version 20
was performed on samples.
RESULTS: MDA increased in both groups. The maximum increase in test group was seen in
concentration 12 mg (MDA Day 14, test [1.93 ± 0.3], [P MDA < 0.001]). Maximum increase in PAB
was seen in concentration 12 mg (from 444 ± 1.7 to 563 ± 2.5) (P PAB = 0.000). Furthermore,
PS expression increased in the concentration of 12 mg greater than other concentration in
consecutive (from 5.00 ± 0.8 to 22.26 ± 1.7, [P < 0.001]).
CONCLUSION: Evaluation of dose dependency showed that different concentrations of antioxidant
NPs affect RBC. This effect can be changed oxidative stress and apoptosis. Using both changes to
evaluate functional and toxicity can be helpful.

Keywords

1. Rudrappan RB, Promotion H. Evaluating the knowledge
and practices of nurses and paramedics in blood transfusion
services – A survey in the states of Tamil Nadu and Pondicherry,
India. 2019;8:48.
2. Meledeo MA, Peltier GC, McIntosh CS, Bynum JA, Cap AP.
Optimizing whole blood storage: Hemostatic function of 35‑day
stored product in CPD, CP2D, and CPDA‑1 anticoagulants.
Transfusion 2019;59:1549‑59.
3. Adams F, Bellairs G, Bird AR, OguntibejuOO. Biochemical storage
lesions occurring in nonirradiated and irradiated red blood cells: a brief review. BioMed research international. 2015 Jan 29;2015.
4. Yoshida T, Prudent M, D’Alessandro AJ. Red blood cell storage
lesion: Causes and potential clinical consequences. Blood Transfus
2019;17:27‑52.
5. Öztaş Y, Boşgelmez İİ. Oxidative stress in sickle cell disease
and emerging roles for antioxidants in treatment strategies.
InPathology 2020 Jan 1 (pp. 65‑75). Academic Press.
6. Ghafouri‑Khosrowshahi A, Ranjbar A, Mousavi L,
Nili‑Ahmadabadi H, Ghaffari F, Zeinvand‑Lorestani H, et al.
Chronic exposure to organophosphate pesticides as an important
challenge in promoting reproductive health: A comparative study.
J Educ Health Promot 2019;8:149.
7. Bhatt S, Nagappa AN, Patil CR. Role of oxidative stress in
depression. Drug Discov Today 2020;25:1270‑6.
8. Chen Z, Tian R, She Z, Cai J, Li H. Role of oxidative stress in the
pathogenesis of nonalcoholic fatty liver disease. Free Radical
Biology and Medicine. 2020 Mar 8 .
9. García‑Sánchez A, Miranda‑Díaz AG, Cardona‑Muñoz EG. The
role of oxidative stress in physiopathology and pharmacological
treatment with pro‑and antioxidant properties in chronic diseases.
Oxid Med Cell Longev 2020; 2020:2082145.
10. Wang Q, Zennadi R. Oxidative stress and thrombosis during
aging: The roles of oxidative stress in RBCs in venous thrombosis.
Int J Mol Sci 2020;21:4259.
11. Nalbant D, Cancelas JA, Mock DM, Kyosseva SV, Schmidt RL,
Cress GA, et al. In premature infants there is no decrease in
24-hour posttransfusion allogeneic red blood cell recovery after
42 days of storage. Transfusion 2018;58:352‑8.
12. D’Alessandro A, Reisz JA, Zhang Y, Gehrke S, Alexander K,
Kanias T, et al. Effects of aged stored autologous red blood cells
on human plasma metabolome. Blood Adv 2019;3:884‑96.
13. Andrabi SS, Yang J, Gao Y, Kuang Y, Labhasetwar V.
Nanoparticles with antioxidant enzymes protect injured spinal
cord from neuronal cell apoptosis by attenuating mitochondrial
dysfunction. J Control Release 2020;317:300‑11.
14. dos Santos Tramontin N, da Silva S, Arruda R, Ugioni KS,
Canteiro PB, de Bem Silveira G, et al. Gold nanoparticles treatment
reverses brain damage in Alzheimer’s disease model. Mol
Neurobiol 2020;57:926‑36.
15. Cappellano G, Comi C, Chiocchetti A, Dianzani U. Exploiting
PLGA‑based biocompatible nanoparticles for next‑generation
tolerogenic vaccines against Autoimmune Disease. Int J Mol Sci
2019;20:204.
16. D’souza AA, Shegokar R. Polyethylene glycol (PEG): A versatile
polymer for pharmaceutical applications. Expert Opin Drug Deliv
2016;13:1257‑75.
17. Fang W, Chi Z, Li W, Zhang X, Zhang Q. Comparative study
on the toxic mechanisms of medical nanosilver and silver ions
on the antioxidant system of erythrocytes: From the aspects
of antioxidant enzyme activities and molecular interaction
mechanisms. J Nanobiotechnology 2019;17:66.
18. Bian Y, Kim K, Ngo T, Kim I, Bae ON, Lim KM, et al. Silver
nanoparticles promote procoagulant activity of red blood cells:
A potential risk of thrombosis in susceptible population. Part
Fibre Toxicol 2019;16:9.
19. Martínez‑Rodríguez NL, Tavárez S, González‑Sánchez ZI. In vitro
toxicity assessment of zinc and nickel ferrite nanoparticles in
human erythrocytes and peripheral blood mononuclear cell.
Elsevier 2019;57:54‑61. [doi: 10.1016/j.tiv. 2019.02.011].
20. Ferdous Z, Beegam S, Tariq S, Ali BH, Nemmar A. The
in vitro effect of polyvinylpyrrolidone and citrate coated silver
nanoparticles on erythrocytic oxidative damage and eryptosis.
Cell Physiol Biochem 2018;49:1577‑88.
21. Ferraro SA, Domingo MG, Etcheverrito A, Olmedo DG, Tasat DR.
Neurotoxicity mediated by oxidative stress caused by titanium
dioxide nanoparticles in human neuroblastoma (SH‑SY5Y) cells.
J Trace Elem Med Biol 2020; 57:126
22. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME,
Peppas NA, Langer R. Engineering precision nanoparticles for
drug delivery. Nat Rev Drug Discov 2020;10:1‑24. [doi: 10.1038/
s41573‑020‑0090‑8].
23. Singhal A, Morris VB, Labhasetwar V, Ghorpade A.
Nanoparticle‑mediated catalase delivery protects human neurons
from oxidative stress. Cell Death Dis 2013;4:e903.
24. Ghayour‑Mobarhan M, Alamdari DH, Moohebati M,
Sahebkar A, Nematy M, Safarian M, et al. Determination of
prooxidant – Antioxidant balance after acute coronary syndrome
using a rapid assay: A pilot study. Angiology 2009;60:657‑62.
25. Martinez Legaspi S, Segatori L. Aggregation behavior of
nanoparticle‑peptide systems affects autophagy. Bioconjug Chem
2019;30:1986‑97.
26. Budama‑KilincY, Cakir‑KocR, ZorluT, OzdemirB, KaraveliogluZ,
Egil AC, Kecel‑Gunduz S. Assessment of Nano‑toxicity and Safety
Profiles of Silver Nanoparticles. Silver nanoparticles‑fabrication,
characterization and applications; Khan, M.; Ed, Intechopen:
London. 2018 Jul 18:185. [doi: 10.5772.intechopen. 75645].
27. Vippola M, Falck GC, Lindberg HK, Suhonen S, Vanhala E,
Norppa H, et al. Preparation of nanoparticle dispersions for
in‑vitro toxicity testing. Hum Exp Toxicol 2009;28:377‑85.
28. Lankoff A, Sandberg WJ, Wegierek‑Ciuk A, Lisowska H,
Refsnes M, Sartowska B, et al. The effect of agglomeration state
of silver and titanium dioxide nanoparticles on cellular response
of HepG2, A549 and THP‑1 cells. Toxicol Lett 2012;208:197‑213.
29. Kittler S, Greulich C, Gebauer JS, Diendorf J, Treuel L, Ruiz L,
Gonzalez‑Calbet JM, Vallet‑Regi M, Zellner R, Köller M, Epple M.
The influence of proteins on the dispersability and cell‑biological
activity of silver nanoparticles. Journal of Materials Chemistry.
2010;20 (3):512‑8. [doi: 10.5772.intechopen. 75645].
30. Sun Y, Liu G, Jiang Y, Wang H, Xiao H, Guan G. Erythropoietin
protects erythrocytes against oxidative stress‑induced eryptosis
in vitro. Clin Lab 2018;64:365‑9.
31. Wadhwa R, Aggarwal T, Thapliyal N, Kumar A, Priya , Yadav P,
et al. Red blood cells as an efficient in vitro model for evaluating
the efficacy of metallic nanoparticles. 3 Biotech 2019;9:279.
32. Kumar V, Sharma N, Maitra SS. In vitro and in vivo toxicity
assessment of nanoparticles. International Nano Letters. 2017
Dec 1;7 (4):243‑56. [doi: 10.5772.59381].
33. KongB, Seog JH, GrahamLM, Lee SB. Experimental considerations
on the cytotoxicity of nanoparticles. Nanomedicine (Lond)
2011;6:929‑41.
34. Muthuraman P, Ramkumar K, Kim DH. Analysis of
dose‑dependent effect of zinc oxide nanoparticles on the oxidative
stress and antioxidant enzyme activity in adipocytes. Appl
Biochem Biotechnol 2014;174:2851‑63.
35. Libi S, Calenic B, Astete CE, Kumar C, Sabliov CM. Investigation
on hemolytic effect of poly (lactic co‑glycolic) acid nanoparticles
synthesized using continuous flow and batch processes.
Nanotechnology Reviews. 2017 Apr 1;6 (2):209‑20. [doi: 10.1515/
ntrev‑2016‑0045].