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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (5): 821-827. doi: 10.19723/j.issn.1671-167X.2020.05.005

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Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles

Di ZHOU,Zhang-jian CHEN,Gui-ping HU,Teng-long YAN,Chang-mao LONG,Hui-min FENG,Guang JIA()   

  1. Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, Beijing 100191, China
  • Received:2018-09-08 Online:2020-10-18 Published:2020-10-15
  • Contact: Guang JIA E-mail:jiaguangjia@bjmu.edu.cn
  • Supported by:
    National Key Research and Development Program of China(2017YFC1600204);National Natural Science Foundation of China(81703257);Excellent Doctoral Training Program of Peking University(BMU20160564)

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Abstract:

Objective: To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. Methods: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. Results: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. Conclusion: TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

Key words: Titanium dioxide, Nanoparticles, Antioxidants, Rats, Sprague-Dawley

CLC Number: 

  • R155.3

Figure 1

Characteristics of the TiO2 nanoparticles A, transmission electron micrographs of TiO2 nanoparticles; B, Feret diameter distribution of TiO2 nanoparticles; C, energy dispersive X-ray spectroscopy (EDS) analysis of elements in TiO2 nanoparticles; D, X-ray powder diffractometer (XRD) spectrogram of TiO2 nanoparticles. Symbols of chemical elements: Ti, titanium; O, oxygen; C, carbon; a.u., arbitrary unit."

Figure 2

Body weight changes in different dose groups (x-±s)"

Figure 3

Average daily food intake in different dose groups (x-±s)"

Table 1

Organ weights coefficients of rats in different dose groups mg/g"

Dose group Lung Spleen Heart Liver Kidney (left) Kidney (right) Testicle (left) Testicle (right) Stomach
Control 4.45±0.16 2.38±0.44 4.07±0.45 31.44±1.61 4.17±0.40 4.07±0.33 4.62±0.41 4.62±0.35 5.57±0.52
Low 4.21±0.18 2.55±0.22 3.90±0.34 31.79±1.77 4.20±0.17 4.20±0.39 4.44±0.50 4.50±0.44 5.73±0.46
Middle 4.31±0.14 2.35±0.30 4.26±0.52 31.32±1.91 3.95±0.20 3.92±0.15 4.62±0.37 4.63±0.31 5.57±0.47
High 4.38±0.34 3.36±0.78 3.83±0.33 31.32±2.43 4.02±0.48 3.98±0.39 4.64±0.23 4.69±0.29 5.61±0.52

Table 2

Effects of TiO2 nanoparticles on oxidation/antioxidation biomarkers in multiple tissues (x-±s)"

Organs Dose
group		 SOD activity/
(U/mg prot)		 GSH concentration/
(μmol/mg prot)		 T-SH concentration/
(nmol/mg prot)		 GSH-Px activity/
(mU/mg prot)		 GSSG
concentration/
(μg/mg prot)		 GSH/GSSG MDA
concentration/
(nmol/mg prot)
Serum Control 4.93±0.67 0.04±0.08 16.31±16.50 43.96±3.80 0.85±0.30 26.26±44.02 105.29±12.48
Low 5.46±0.98 0.03±0.09 39.93±21.04 46.37±2.65 1.14±1.03 19.11±46.80 104.85±11.33
Middle 5.49±0.54 0.06±0.13 28.05±6.59 35.27±2.35 0.56±0.64 31.70±70.88 106.19±12.22
High 6.39±0.41# 0.01±0.02 30.93±15.14 37.75±8.58 0.85±0.71 5.30±12.99 98.30±22.96
Liver Control 0.11±0.21 20.76±2.85 238.50±26.65 5.83±5.04 21.39±7.62 647.68±207.22 26.91±4.24
Low 0.17±0.26 23.55±3.66 256.30±33.03 0.56±5.97 17.24±7.51 930.27±287.26 36.95±5.90*
Middle 0.09±0.13 19.86±2.63 201.95±12.85 3.43±6.34 16.76±5.09 760.92±166.55 29.21±6.71
High 0.48±0.39 20.81±2.41 220.02±33.59 4.81±4.57 17.02±3.68 774.08±147.36 38.39±5.18*
Intestine Control 1.44±0.33 9.82±5.89 36.03±19.73 8.40±6.66 11.06±2.82 515.36±163.14 43.79±4.46
Low 1.73±0.84 14.93±10.55 48.93±22.81 6.43±12.56 15.49±6.16 577.13±327.83 40.30±5.76
Middle 1.33±0.53 18.16±9.31 52.53±19.20 4.00±11.21 20.66±4.35* 518.63±212.59 35.11±5.93
High 1.54±0.44 14.02±7.06 52.21±21.23 10.37±14.18 17.16±3.19* 481.50±172.02 41.23±6.85
Colon Control 2.49±0.54 15.80±10.67 33.12±11.23 11.39±10.20 13.50±6.96 416.51±286.73 41.73±7.35
Low 2.64±0.51 13.94±4.36 22.07±17.25 21.44±7.07 18.79±8.88 395.07±170.72 50.98±6.47
Middle 2.15±0.31 15.85±1.14 9.83±11.10 16.79±9.37 19.11±4.12 528.24±124.51 44.21±6.04
High 2.29±0.20 15.14±3.11 24.90±19.19 13.66±6.95 16.61±4.85 550.59±157.70 54.55±8.76

Table 3

Effects of TiO2 nanoparticles on inflammatory cytokine in multiple tissues (x-±s)"

Organs Dose group IL-6 concentration/
(pg/mg prot)		 TNF-α concentration/
(pg/mg prot)
Serum Control 0.14±0.30 12.20±7.60
Low 0.13±0.31 8.37±5.39
Middle 0.51±0.79 7.97±3.95
High 0.00±0.00 13.80±7.57
Liver Control 413.46±73.80 296.50±86.11
Low 438.00±95.87 747.11±326.80
Middle 420.42±66.59 599.45±64.11#
High 448.55±27.43 608.23±129.06#
Intestine Control 6.34±15.53 10.77±26.38
Low 12.15±40.51 8.93±21.87
Middle 24.85±43.44 27.13±44.93
High 3.47±31.66 38.63±63.20
Colon Control 22.87±17.74 28.16±29.31
Low 24.87±21.56 36.62±37.72
Middle 39.57±10.24 48.92±14.54
High 26.06±13.83 25.66±21.71
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