Annals of Tropical Medicine and Public Health

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 10  |  Issue : 3  |  Page : 618--622

Study of the administration impact of titanium dioxide nanoparaticles during pregnancy on hemetological parameters and lipid profile in the mice offspring


Mazyar Fathi1, Faramarz Jalili2, Parnian Jalili3, Mohammad Reza Salahshoor4, Mahdi Taghadosi5, Maryam Sohrabi1, Fariborz Bahrehmand6, Cyrus Jalili4,  
1 Department of Anatomy, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Faculty of Medicine, Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
4 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
5 Department of Immunology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
6 Department of Biochemistry, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Correspondence Address:
Cyrus Jalili
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah
Iran

Abstract

Introduction: Nanotechnology is a developing technology whose use is increasing in different aspects. Among various nanostructures that are widely used, we can refer to titanium dioxide nanoparticles (Tio2-np), which are applied in water and wastewater treatment, antibacterial and antifungal substances, and self-cleaning surfaces; however, due to passing of the particles through placenta and blood–brain barrier, it may cause pathological damages in infants and affect the future generations' health. Objective: The aim of this study is to investigate the impact of administration of titanium dioxide nanoparticles during pregnancy on hematological parameters and lipid profile in the mice offspring. Materials and Methods: In this experiment, 30 female mice were divided into three groups, including the control group who received no substance, the solvent group who received drug carrier on the 3rd, 7th, 10th, and 14th days of pregnancy, and the treatment group who received subcutaneously 10 μL of titanium dioxide nanoparticles of 1 mg/mL concentration in the 3rd, 7th, 10th, and 14th days after mating. Afterwards, among the offspring of each group, 10 male and 10 female offspring were chosen to evaluate hematological parameters and lipid profile on the 42nd day. Results: The results demonstrated that offspring exposure to prenatal titanium dioxide particles (Tio2-NP) in the treatment group causes changes in hematological parameters and lipid profile levels in male and female offspring; however, changes were greater in female offspring. Conclusion: Since previous studies have shown that titanium dioxide nanoparticles have the ability to cross the placenta and blood–brain barrier. After passing the barriers, they cause damages to various organs including liver and kidney and also changes in gene expression levels in different parts of the body including brain and bones. In addition, they result in producing free radical in the body and developing disorders in globules production and lipid metabolism.



How to cite this article:
Fathi M, Jalili F, Jalili P, Salahshoor MR, Taghadosi M, Sohrabi M, Bahrehmand F, Jalili C. Study of the administration impact of titanium dioxide nanoparaticles during pregnancy on hemetological parameters and lipid profile in the mice offspring.Ann Trop Med Public Health 2017;10:618-622


How to cite this URL:
Fathi M, Jalili F, Jalili P, Salahshoor MR, Taghadosi M, Sohrabi M, Bahrehmand F, Jalili C. Study of the administration impact of titanium dioxide nanoparaticles during pregnancy on hemetological parameters and lipid profile in the mice offspring. Ann Trop Med Public Health [serial online] 2017 [cited 2019 Nov 21 ];10:618-622
Available from: http://www.atmph.org/text.asp?2017/10/3/618/213121


Full Text

 Introduction



In recent years, the use of nanoparticles particularly titanium dioxide nanoparticles has been increased due to their numerous applications in water waste, paint manufacturing, sterilization, food additives, and medical as well as dental uses. Because of the small size and increased surface in proportion to volume, they have increased chemical reactivity. Titanium dioxide nanoparticles can enter human's body and threaten the health.[1],[2] Earlier studies have demonstrated that titanium dioxide nanoparticles lead to the production of free radicals due to their photo catalytic property.[3] The study of human's placenta perfusion model confirmed that nanoparticles have the ability to cross the placenta using endocytosis [4] and placental damages caused by nanoparticles can potentially result in fetal developmental defects or retardation.[5] Additionally, exposure to nanoparticles during pregnancy may affect fetus organogenesis and morphology.[6] Fabian et al. (2008) reported that following the intravenous injection of titanium dioxide to living organisms, these particles enter the circulatory system and then move to other organs thereby causing various complications.[7] Furthermore, during an experiment, inflammation and the increased release of cytokines and free radicals were observed in mice when titanium dioxide nanoparticles were administered [8] and it was indicated that when pregnant mice were exposed to these nanoparticles, the expression of the genes associated with growth, cell death, and also genes related to oxidative stress response were changed in infants.[9] Previous studies have demonstrated that these nanoparticles cause increase in lipoprotein oxidation which might lead to the increased atherosclerosis.[10] Additionally, Tio2-np causes the changes in lipoprotein lipase activity and lipid profile content in liver of adult mice.[11] It has been shown in the previous studies that Tio2-np administration to male adult mice would result in changes in hematologic parameters and affect the circulatory system.[12] Due the fact that the nanoparticles have the ability to cross the placental barrier and reach the fetus, determining the particles side effects on different parts of the body including hematologic parameters of body and liver is necessary and having knowledge about them is regarded as an accurate and sensitive means to understand and monitor the physiological and pathological changes in humans and animals.

 Materials and Methods



Preparing titanium dioxide nanoparticles

Titanium dioxide nanoparticles (in the anatase form, the size of 12 nm, and purity of 99.9%) were provided from US Research Nanomaterial, Inc. and prepared in saline containing 0.05% Tween80, in the solution form. Morphologic features and TiO2-NP size were examined, measured, and assessed by the scanning electron microscope whose image is shown in [Figure 1]. Nanoparticles were dissolved in the sonicator device with ultrasonic waves at least half an hour before the solution injection.[13]{Figure 1}

Animals

In total 30 NMRI 7-week old female mice were obtained from Medical University of Kermanshah. The animals were kept at 22 ± 2°C and in a 12 hr light/12 hr dark cycle with free access to food and water. For the concurrence of sexual cycles, mice passed matching period for 2 weeks. After 2 weeks, two male mice in proportion to every five female mice were added to the cage and after observing vaginal plug, mice with vaginal plug were marked. After 2-3 years, pregnant mice were transferred to separate cages and they were divided into four different groups with 10 pregnant mice in each group.

Control group: control group did not receive any substances.

Solvent group: drug control group received subcutaneously 100 μL of saline solution containing 0.05%Tween 80 (carrier) in the 3rd, 7th, 10th, and 14th days following mating.[9]

Treatment group: They received subcutaneously 100 μL of TiO2-NP solution with 1 mg/mL concentration in the 3rd, 7th, 10th, and 14th days following mating.

Hematological parameters

After pregnancy and offspring birth, 10 male and 10 female offspring of each group were selected randomly for taking blood sample and anesthetized deeply with ketamine/xylazine (the ratio of 100 to 30). Heart blood samples were taken and collected in tubes containing sodium citrate and transferred instantly to the automatic cell counter for counting blood cells and the following factors were calculated: white blood cells (WBC), lymphocyte (LYM), granulocyte (GRAN), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), platelets (PLT), and mean platelet volume (MPV).

Lipid profile

Some of the collected blood was placed in the centrifuge at 3000 rpm for 15 min and plasma was kept at –20°C until testing and free fatty acids were measured using the Felix method.[13]

Analysis

After gathering data, statistical analyses were performed using the SPSS software, 1-way ANOVA (analysis of variance), and Duncan post hoc test (P < 0.05).

 Results



The results of hematologic studies indicated that the WBC level in both groups, male offspring (MT) and female offspring (FT) of treatment group, was significantly reduced compared with the control group offspring [Table 1] and [Table 2]. The LYM level in mice of MT and FT groups showed a significant decrease compared with the control group; however, there was a significant decrease of the LYM percentage just in the FT mice group [Table 1] and [Table 2]. The percentage of GRAN level in the FT group showed a significant increase compared to the control group, but the increase of granulocytes percentage was not significant in the MT group [Table 2]. In the case of the red blood cells, there was a significant decrease of MCH and MCHC levels in the FT group compared with the control group; however, this decrease in mice of MT group compared with control group was not significant [Table 2]. The MCV level in both FT and MT groups had significantly increased in comparison with control groups, whereas in the case of RDW%, MPV, and RBC factors, no significant differences were found between the groups [Table 1] and [Table 2]. In the case of platelets, PLT levels in both FT and MT groups had shown a greatly significant increase compared with control groups; however, the MPV level presented no differences in groups [Table 1] and [Table 2]. Lipid profile analysis indicated that cholesterol, triglyceride, and LDL levels in FT and MT groups were significantly increased compared with control groups and the HDL level decreased significantly [Table 3] and [Table 4].{Table 1}{Table 2}{Table 3}{Table 4}

 Discussion



In the present study, mice offspring in the prenatal period were exposed to titanium dioxide nanoparticles of 1 mg/mL concentration with a dose of 100 μL to evaluate their effects on hematologic parameters and lipid profile, which are among important factors in physiopathology. In this study, it was indicated that WBC and LYM levels reduced in male and female offspring of treatment group with TiO2-NP administration. Additionally, a previous study conducted by Duan et al. demonstrated that administration of TiO2-NP to adult mice led to a significant decrease in WBC in the animals.[12] Furthermore, Cheraghi et al. in a study, in which the adult male and female mice were gavaged with silver nanoparticles, came to the conclusion that the particles leads to the decreased WBC level.[14] The decreased WBC level might be due to the suppressive impact of nanoparticles on stem cells in bone marrow. Kang et al. evaluated the effect of TiO2 on human's cultured peripheral blood lymphocyte cells. They showed that these nanoparticles cause damage to peripheral lymphocyte DNA due to the production of ROS which ultimately leads to death of the cells.[15] In the recent study, based on the decreased MCHC and the increased MCV in female offspring, it can be concluded that the offspring suffer a kind of macrocytic and hypochromic anemia that increased MCV be due to delayed mitotic cycle as a result of DNA damage by titanium dioxide nanoparticles. In this regard, Trouiller et al. revealed in a study that TiO2-NP caused damage to bone marrow DNA of offspring exposed to these particles during the fetal period and that the damage can result in production of free radicals or inflammatory reaction.[16] In an experiment conducted by Saghiri et al., it was shown that the intraperitoneal injection of TiO2 nanoparticles to adult mice led to damage and abnormality in their bone marrow which ultimately affected the production of different types of blood cells in bone marrow.[17] In addition, it was indicated in this experiment that the platelet level in male and female offspring had raised dramatically when compared with the control group and this sharp rise might cause a disorder in the circulatory system and indicate the possible effect of TiO2 nanoparticles on the coagulation system. The particles also might affect the platelet metabolism in bone marrow and cause the increased platelet production which might finally result in increased thrombosis and the disorder in the circulatory system.[18] The former studies have proven that adult mice exposure to the nanoparticles led to the increased platelet level in the circulatory system.[19],[20] In the present study, it has been indicated that TiO2 nanoparticles affect offspring lipid metabolism and these lipid changes happen due to the impact of the particles on lipoprotein lipase or tissue transferring and removing of lipid fractions. It was further shown in a study conducted by Ani et al. that these nanoparticles cause changes in this enzyme.[11] Although lots of changes were observed in the lipid profile in terms of importance, LDL increase might be clinically regarded as the most significant change. Additionally, it has been clearly indicated that there is a direct association between lipoprotein and cardiovascular diseases.[21] Numerous studies have revealed that the increased ratio of LDL/HDL has a direct association with arteriosclerosis.[21],[22] Therefore, it was demonstrated in the present experiment that exposing to TiO2 nanoparticles can increase the probability of affliction with cardiovascular diseases and arteriosclerosis.

 Conclusion



Based on the current data, it can be concluded that maternal exposure to TiO2 nanoparticles results in a disorder in blood cells and lipoprotein profile metabolism in offspring; accordingly, pregnant mothers' exposure to the particles should be decreased and the particles should also be produced and used cautiously in industry and medicine.

Financial support and sponsorship

Nil

Conflicts of interest

There are no conflicts of interest.

References

1Banfield JF and Zhang H. Nanoparticles in the environment. Rev Mineralo Geochem 2001;44:1–58.
2Fujishima A, Zhang X, Tryk DA. TiO 2 photocatalysis and related surface phenomena. Surface Science Reports 2008;63:515-82.
3Wick P, Malek A, Manser P, Meili D, Maeder-Althaus X, Diener L, et al. Barrier capacity of human placenta for nanosized materials. Environ Health Perspect 2010;118:432-6.
4Sun J, Zhang Q, Wang Z, Yan B. Effects of nanotoxicity on female reproductivity and fetal development in animal models. Int J Mol Sci 2013;14:9319-37.
5Tsuchiya T, Oguri I, Yamakoshi YN, Miyata N. Novel harmful effects of [60] fullerene on mouse embryos in vitro and in vivo. FEBS Lett. 1996;393:139-45.
6Fabian E, Landsiedel R, Ma-Hock L, Wiench K, Wohlleben W, van Ravenzwaay B. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol 2008;82:151-7.
7Wang JX, Li YF, et al. Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time. Zhonghuayu fang yixuezazhi Chinese J Prevent Med 2007;41:91–5.
8Shimizu M, Tainaka H, et al. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre Toxico 2009;l6:20.
9Ani M, Moshtaghie AA, et al. Comparative effects of copper, iron, vanadium and titanium on low density lipoprotein oxidation in vitro. Iran Biomed J 2007;11:113–8.
10Ani A, Ani M, et al. Changes in liver contents of lipid fractions following titanium exposure. Iranian J Pharm Res 2008;179–83.
11Duan Y, Liu J, et al. Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials 2010;31:894–9.
12Felix W. Lipase photometric assay. In: Bergmeyer HU Methods Enzymatic Anal 1974;3:819-27.
13Cheraghi J, Hosseini E, et al. Hematologic parameters study of male and female rats administrated with different concentrations of silver nanoparticles. Int J Agric Crop Sci 2013;5:789.
14Kang SJ, Kim BM, et al. Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 2008;49:399–405.
15Trouiller B, Reliene R, et al. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res 2009;69:8784–9.
16Saghiria Z, Saleh-Moghadama M, et al. Effect evaluation of anatase TiO2 nanoparticles on induction of chromosomal damage in mice bone marrow in Vivo. The 4th International Conference on Nanostructures; 2012.
17Ziapour A, Khatony A, Jafari F, Kianipour N. Patient Satisfaction with medical services provided by a hospital in Kermanshah-Iran. Acta Med Mediterranea 2016;32:959–65.
18Nemmar A, Melghit K, et al. Acute respiratory and systemic toxicity of pulmonary exposure to rutile Fe-doped TiO 2 nanorods. Toxicology 2011;279:167–75.
19Duan Y, Liu J, et al. Toxicological characteristics of nanoparticulateanatase titanium dioxide in mice. Biomaterials 2010;31:894–9.
20Parthasarathy S, Barnett J, et al. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta 1990;1044:275–83.
21Bonnefont-Rousselot D, Therond P, et al. High density lipoproteins (HDL) and the oxidative hypothesis of atherosclerosis. Clin Chem Lab Med 1999;37:939–48.
22Kapur NK, Ashen D, Blumenthal RS. High density lipoprotein cholesterol: An evolving target of therapy in the management of cardiovascular disease. Health Risk Manag 2008;4(1):39-57.