View of Clinicohematological Study of Gold Nanoparticles Toxicity and Ameliorative Effect of Allium Sativum

Download (0)

Full text


Clinicohematological Study of Gold Nanoparticles Toxicity and Ameliorative Effect of Allium Sativum

Samed Abduljabbar Ramadhan


, Ozdan Akram Ghareeb



Department of Nursing Techniques, Institute of Medical Technology-Baghdad, Middle Technical University, Iraq .


Department of Community Health Techniques, Kirkuk Technical Institute, Northern

Technical University, Iraq.


Administration of chemical substances at toxic doses usually lead to blood parameter alterations, which indicates occurrence of hematological disorders like anaemia. In addition to the positive effects of nanoparticles, they are considered as potential hazardous agents to human's health. In the present study, (24) healthy albino rats were divided into 4 groups, 6 rats for each. The control animals included rats without treatment, while the GNPs group rats received gold nanoparticles. GNPs +AS group rats were co-administrated with a combination of GNPs with Allium sativum.

The AS group animals were treated with A. sativum only. Blood parameters were measured to find the negative effects of gold nanoparticles. Results in the GNPs group showed that the hematological parameters were significantly decreased (p<0.05) including the red blood cell count (RBCs), hemoglobin (Hb) concentration, hematocrit value (Hct) and platelet count (PLTs), while the white blood cell count (WBCs) showed a significant increase in comparison to the control group. The co-administration of A. sativum along with GNPs exerted a significant modulation in all hematological disorders. Therefore, these results demonstrated that A. sativum has shown a defensive impact against GNPs induced hematological alterations in male rats.

Keywords: Gold nanoparticles, blood parameters, Allium sativum.


Gold nanoparticles (GNPs) have various applications in the medical field


. Several reports revealed the presence of toxic impacts of nanoparticles in vivo, although nanoparticles are known to be safe materials


. At the (1–100 nm)


Nano scale, materials are different from their bigger counterparts as they are more reactive owing to the relatively high surface to diameter ratio


. The evaluation of hematologic parameters is essential to determine gold nanoparticle toxicity


. Under certain conditions, it is difficult to translate the adverse impacts from animal to human, but the detection of animal's blood parameters is of great predictive value for human toxicity



Till now, herbs are used mainly in the treatment in several developing country for primary health care

due to their excellent culturing compatibility and acceptance in the human body as well as their lesser side



. Allium sativum L., Family: Amaryllidacae is the scientific name of garlic, which is the aromatic

annual spice herb and the oldest authenticated and most essential herbal plant which was used from ancient

times in traditional medical treatments


.The existence of sulfur containing chemicals in garlic provides

substantial anti-inflammatory, immunomodulatory, antitumor, anticancer, antidiabetic, anti-atherosclerotic

as well as cardio protective features




Materials and Methods


Gold (Au) Nanopowder Water Dispersion was purchased from US Research Nanomaterials, Inc. Company (Houston, TX, USA). Particle Average Size: 14 nm, PH= 7±0.5, Purity: 99.99 %.


went through a rigorous scientific preparation process of Nano gold productions in aqueous solutions. A 50 μL (0.25 mL/kg/day) dose was administered intraperitoneally to the rats


. Allium sativum was obtained in the form of Odorless Garlic powder from pure, healthy and odorless garlic plant USA.

In vivo experimental design

In this study, (24) adult male albino rats with weighing (200-215 gm) were used. Animals were housed in humidity and temperature-controlled ventilated cages on 12 hour light–12 hour dark cycles, with free access to the standard laboratory rats’ water & diet. The animals have been divided randomly into 4 groups (6 animals in each group): The control animals included normal healthy rats; the (GNPs) group included rats received GNPs; the (GNPs+AS) group included GNPs intoxicated rats treated with A. sativum at 300 mg/kg bw


; (AS) group included animals which were given A. sativum at 300 mg/kg dose alone, for 14 consecutive days. The animals received their daily doses for 14 consecutive days. At the end of the experiment, animals were sacrificed. Blood was collected by cardiac puncture in (EDTA) containing tubes for performing complete blood count.

Complete blood count

The estimation of red blood cell counts (RBCs), hemoglobin (Hb) concentrations, hematocrit values (Hct), platelet counts (PLTs) and white blood cell counts (WBCs) were performed by the automatic hematology analyzer.

Statistical analysis

The obtained results were performed as mean (±) standard deviation (n=6). The statistical significance between the different groups was analyzed using the one way analysis of variance (ANOVA) followed by Duncan multiple range analysis.


Results of the experimental groups showed significantly lower red blood cell counts (RBCs), hemoglobin (Hb) concentration, hematocrit value (Hct) and platelet count (PLTs) in the GNPs group (p<0.05).

Leukocytosis was evident in GNPs intoxicated rats, as shown in figure (2). This finding indicates that the

blood is slightly altered with the administration of GNPs. Co-administration of A. sativum to GNPs rats

significantly improved all these hematological parameters (p<0.05) when compared with the GNPs

intoxicated rats.


Figure (1): Levels of (a): red blood cells count RBCs, (b): hemoglobin Hb, (c): hematocrit value Hct, (d):

platelets count PLTs and (e): white blood cell count WBCs in the blood of different animal groups. a–d Different superscript letters denote significant differences within a column (p<0.05).


Haematopathology is a laboratory medical practice and science which is concerned with the study, investigation and diagnosis of blood disorders. The functional characteristics of hematological parameters are altered because of adding altered tissue and biochemical product to blood and their interaction with the blood component


. The first physiologic system that gold nanoparticles interact with after administration is blood & blood components. The gold nanoparticles are able to stimulate inflammatory responses and decrease or increase the immune system's activities and change related hematological parameters e.g blood cell count. The alterations in the physicochemical characteristics including form, length, combination, chemical make-up, high specific surface area & solubility were because of the toxicity induced by

0 1 2 3 4 5 6 7


RBCs 10 6 cell/µl)


0 2 4 6 8 10 12 14


HB ( gm/dl )


0 10 20 30 40 50 60


HCT ( % )


0 0.5 1 1.5 2 2.5 3 3.5 4 4.5


PLTs 10 5celll)


0 2 4 6 8 10 12


WBCs ( ×103celll )





. Hemoglobin is the main intracellular protein in the red cell, which is synthesized in bone marrow. Low hemoglobin concentration may result from blood loss or immature reticulocytes or accelerated red blood cell destruction, leading to anaemia


. Bone marrow is the site of platelet production and therefore, their counts may be reduced in diseases of bone marrow as well as anaemia. Circulating platelets may be decreased (thrombocytopenia) by either decreased production or increased platelet destructions


. Hematocrit, the volume of red blood cells in a column of whole blood and is clinically used for detection of suspected or known anemia. Factors affecting red cells will have effect on the haematocrit since red cells constitute 99% of the whole blood cells. Hematocrit is the main measure of blood viscosity


. A hematocrit value below the normal represents anemia .This may be resulted from a reduction in the erythrocyte count, a decrease in the hemoglobin concentration in each red cell, or both. It often occurs due to myeloid tissue damage by chemicals like toxins, which inhibit enzymes required for haemopoiesis


. The white cells (WBCs) are responsible for body's immunity against antigenic invasions. These white cells are synthesized in the bone marrow from a pluripotent hematopoietic stem cell (myeloid)

33, 34

. The usual inflammatory response includes white cell accumulation, in the site of foreign particle position to remove cells selectively and restore homeostasis


. The hematological parameters were shown to be significantly improved in the GNPs + A. sativum group when compared with the GNPs group. This might be attributed to the organosulfur compound (OSC) in the garlic. This compound plays an essential role in preventing different pathological progressions


. Several experiments demonstrated the anti-inflammatory characteristics of (OSC) and highlighted their indirect mechanisms as well as providing chemoprotections


. Thus, this study revealed that A. sativum acts as a protective agent against blood disorders caused by hematotoxicity of GNPs.


It can be concluded from the current study that gold nanoparticles have toxic effects on blood components.

Here, we have discussed the probability of blood toxicity reduction by using A. sativum as herbal plant. Our findings showed that garlic may have an important role in ameliorating heamatotoxicity.


1- Yahyaei B, Nouri M, Bakherad S, Hassani M, Pourali P. Effects of biologically produced gold nano particles:

toxicity assessment in different rat organs after intraperitoneal injection. AMB Express. 2019 Dec 1;9(1):38.

2- Pourali P, Badiee SH, Manafi S, Noorani T, Rezaei A, Yahyaei B. Biosynthesis of gold nanoparticles by two bacterial and fungal strains, Bacillus cereus and Fusarium oxysporum, and assessment and comparison of their nanotoxicity in vitro by direct and indirect assays. Electronic Journal of Biotechnology. 2017 Sep 1;29:86-93.

3- Kzar AJ. Antimicrobial and Biofilm Inhibitory Activity of Nanoparticles Against Clinical Isolates from Urinary Tract Infection. Indian Journal of Forensic Medicine & Toxicology. 2020 Jul 30 ; 14 (3):194-9.

4- Jeevanandam J, Barhoum A, Chan YS, Dufresne A, Danquah MK. Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations. Beilstein journal of nano technology. 2018 Apr 3;9(1):1050-74.

5- Ziaee Ghahnavieh M, Ajdary M, Ziaee Ghahnavieh M, Naghsh N. Effects of intraperitoneal injection of gold nanoparticles in male mice. Nanomedicine Journal. 2014;1(3):121-7.

6- Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regulatory Toxicology and Pharmacology. 2000 Aug 1;32(1):56-67.


7- Donma MM, Donma O. The Effects of Allium Sativum on Immunity within the Scope of COVID-19 Infection. Medical Hypotheses. 2020 Jun 2:109934.

8- El-Saber Batiha G, Magdy Beshbishy A, G Wasef L, Elewa YH, A Al-Sagan A, El-Hack A, Mohamed E, Taha AE, M Abd-Elhakim Y, Prasad Devkota H. Chemical constituents and pharma cological activities of garlic (Allium sativum L.): A review. Nutrients. 2020 Mar;12(3):872.

9- El-Saber Batiha G, Magdy Beshbishy A, Wasef LG, Elewa YH, Al-Sagan AA, El-Hack A, et al. Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients.

2020;12(3):872. doi: 10.3390/nu12030872.

10- Khubber S, Hashemifesharaki R, Mohammadi M, Gharibzahedi SM. Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19. Nutrition Journal. 2020 Dec;19(1):1-3.

11- Miękus N, Marszałek K, Podlacha M, Iqbal A, Puchalski C, Świergiel AH. Health Benefits of Plant-Derived Sulfur Compounds, Glucosinolates, and Organosulfur Compounds. Molecules. 2020 Jan;25(17):3804.

12- Abdelhalim MA, Moussa SA, Qaid HA. The protective role of quercetin and arginine on gold nanoparticles induced hepatotoxicity in rats. International Journal of Nanomedicine. 2018; 13: 2821 .

13- El-Sebaey AM, Abdelhamid FM, Abdalla OA. Protective effects of garlic extract against hematological alterations, immunosuppression, hepatic oxidative stress, and renal damage induced by cyclophosphamide in rats. Environmental Science and Pollution Research. 2019 May 1;26(15):15559-72.

14- Catalano Jr EW, Ruby SG, Talbert ML, Knapman DG. College of American Pathologists considerations for the delineation of pathology clinical privileges. Archives of pathology & laboratory medicine. 2009


15- Arika WM, Nyamai DW, Musila MN, Ngugi MP, Njagi EN. Hematological markers of in vivo toxicity.

Journal of Hematology&Thromboembolic Diseases. 2016 Mar 29.

16- Zhang XD, Wu HY, Di Wu YY, Chang JH, Zhai ZB, Meng AM, Liu PX, Zhang LA, Fan FY. Toxicologic effects of gold nanoparticles in vivo by different administration routes. International journal of nanomedicine.


17- Gjetting T, Arildsen NS, Laulund C, et al. In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/ cholesterolmediated gene transfection. Int J Nanomedicine. 2010;5:371–383.

18- Hauck TS, Anderson RE, Fischer HC, Newbigging S, Chan WCW. In vivo quantum-dot toxicity assessment.

Small. 2010; 6:138–144.

19- Mokgalaboni K, Mabusela MS, Moraba MM. Haematological Indices and Anaemia in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis.

20- Kolanjiappan K, Manoharan S, Kayalvizhi M. Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients. Clinica Chimica Acta. 2002 Dec 1;326(1-2):143- 9.

21- Chaparro CM, Suchdev PS. Anemia epidemiology, pathophysiology, and etiology in low-and middle-income countries. Annals of the New York Academy of Sciences. 2019 Aug;1450(1):15.

22- Randi ML, Bertozzi I, Santarossa C, Cosi E, Lucente F, Bogoni G, Biagetti G, Fabris F. Prevalence and Causes of Anemia in Hospitalized Patients: Impact on Diseases Outcome. Journal of Clinical Medicine. 2020 Apr;9(4):950.

23- Barrera‐Reyes PK, Tejero ME. Genetic variation influencing hemoglobin levels and risk for anemia across populations. Annals of the New York Academy of Sciences. 2019 Aug;1450(1):32-46.

24- Guinn NR, Cooter ML, Weiskopf RB. Lower hemoglobin concentration decreases time to death in severely anemic patients for whom blood transfusion is not an option. Journal of Trauma and Acute Care Surgery.


26- Grodzielski M, Goette NP, Glembotsky AC, Pietto MC, Méndez-Huergo SP, Pierdominici MS, Montero VS, Rabinovich GA, Molinas FC, Heller PG, Lev PR. Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia. Scientific reports. 2019 Feb 18;9(1):1-0.

27- Mahévas M, Moulis G, Andres E, Riviere E, Garzaro M, Crickx E, Guillotin V, Malphettes M, Galicier L, Noel N, Darnige L. Clinical characteristics, management and outcome of COVID‐19‐associated immune thrombocytopenia: a French multicentre series. British journal of haematology. 2020 Aug;190(4):e224-9.

28- Kado R, McCune WJ. Treatment of primary and secondary immune thrombocytopenia. Curr Opin Rheumatol.

2019 May;31(3):213-222.

29- Kishimoto S, Maruhashi T, Kajikawa M, Matsui S, Hashimoto H, Takaeko Y, Harada T, Yamaji T, Han Y, Kihara Y, Chayama K. Hematocrit, hemoglobin and red blood cells are associated with vascular function and vascular structure in men. Scientific reports. 2020 Jul 10;10(1):1-9.

30- Mehri R, Mavriplis C, Fenech M. Red blood cell aggregates and their effect on non-Newtonian blood viscosity at low hematocrit in a two-fluid low shear rate microfluidic system. Plos one. 2018 Jul 19;13(7):e0199911.

31- Weisel JW, Litvinov RI. Red blood cells: the forgotten player in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis. 2019 Feb;17(2):271-82.

32- Greim H, Kaden DA, Larson RA, Palermo CM, Rice JM, Ross D, Snyder R. The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment. Annals of the New York Academy of Sciences. 2014 Mar;1310(1):7.

33- Zheng XT, Tan YN. Development of Blood‐Cell‐Selective Fluorescent Biodots for Lysis‐Free Leukocyte Imaging and Differential Counting in Whole Blood. Small. 2020 Mar;16(12):1903328.

34- Irimia D, Wang X. Inflammation-on-a-Chip: probing the immune system ex vivo. Trends in biotechnology.

2018 Sep 1;36(9):923-37.

35- Kumar V, Abbas AK, Fausto N, Aster JC. Robins and Cortan Pathologic Basis of Disease. Inflammation and Repair. 9th ed. Philadelphia, PA: Elsevier health sciences (2014). p. 69–112.

36- Patel H, Patel V. Inflammation and metabolic syndrome-an overview. Curr Res Nutr Food Sci J. (2015) 3:263–8.

37- Miękus N, Marszałek K, Podlacha M, Iqbal A, Puchalski C, Świergiel AH. Health Benefits of Plant-Derived Sulfur Compounds, Glucosinolates, and Organosulfur Compounds. Molecules. 2020 Jan;25(17):3804.

38- Ruhee RT, Roberts LA, Ma S, Suzuki K. Organosulfur compounds: A review of their anti-inflammatory effects in human health. Frontiers in Nutrition. 2020;7.

39- Chowdhury R, Dutta A, Chaudhuri SR, et al. In vitro and in vivo reduction of sodium arsenite induced toxicity by aqueous garlic extract. Food Chem Toxicol. 2008;46(2):740–751.




Related subjects :