Silica nanoparticles induce cardiomyocyte apoptosis via the mitochondrial pathway in rats following intratracheal instillation

Du,Zhongjun; Chen,Shangya; Cui,Guanqun; Yang,Ye; Zhang,Enguo; Wang,Qiang; Lavin,Martin F.; Yeo,Abrey J.; Bo,Cunxiang; Zhang,Yu; Li,Chao; Liu,Xiaoshan; Yang,Xu; Peng,Cheng; Shao,Hua

doi:10.3892/ijmm.2018.4045

Silica nanoparticles induce cardiomyocyte apoptosis via the mitochondrial pathway in rats following intratracheal instillation

Authors:
- Zhongjun Du
- Shangya Chen
- Guanqun Cui
- Ye Yang
- Enguo Zhang
- Qiang Wang
- Martin F. Lavin
- Abrey J. Yeo
- Cunxiang Bo
- Yu Zhang
- Chao Li
- Xiaoshan Liu
- Xu Yang
- Cheng Peng
- Hua Shao
View Affiliations

Affiliations: Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, Ji'nan, Shandong 250062, P.R. China, Department of Respiratory Medicine, Qilu Children's Hospital of Shandong University, Ji'nan, Shandong 250012, P.R. China, Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Radiology, Shandong Tumor Hospital, Shandong Academy of Medical Sciences, Ji'nan, Shandong 250117, P.R. China
Published online on: December 31, 2018 https://doi.org/10.3892/ijmm.2018.4045
Pages: 1229-1240
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Diseases of the cardiac system caused by silicon dioxide exposure have captured wide public attention. Upon entering the blood circulation, ultrafine particles have the potential to influence cardiomyocytes, leading to myocardial ischemia or even cardiac failure, and the molecular mechanisms remain to be completely elucidated. In this study, the toxicity of ultrafine particles on cardiomyocytes from rats exposed to silica nanoparticles was observed. Rats were randomly divided into a normal saline control group and three exposure groups (2, 5 and 10 mg/kg·body weight) that were intratracheally treated with 60‑nm silica nanoparticles. Alterations in body weight, routine blood factors and myocardial enzymes, histopathological and microstructural alterations, apoptosis and the expression of apoptosis‑associated proteins were assessed at the end of the exposure period. The silicon levels in the heart and serum, and myocardial enzymes in exposed rats were significantly increased in a dose‑dependent manner. In addition, exposure to the silica nanoparticles caused notable histological and ultrastructural alterations in the hearts of these animals. Furthermore, a significant apoptotic effect was observed in the exposure groups. The present data suggest that silica nanoparticles may enter the circulatory system through the lungs, and are distributed to the heart causing cardiovascular injury. Silica nanoparticle‑induced apoptosis via the mitochondrial pathway may serve an important role in observed cardiac damage.

View Figures

View References

1	Lasfargues M, Stead G, Amjad M, Ding Y and Wen D: In Situ production of copper oxide nanoparticles in a binary molten salt for concentrated solar power plant applications. Materials (Basel). 10. pp. E5372017, View Article : Google Scholar
2	Ortelli S, Costa A and Dondi M: TiO2 nanosols applied directly on textiles using different purification treatments. Materials (Basel). 8:7988–7996. 2015. View Article : Google Scholar
3	Oliveira MLS, Navarro OG, Crissien TJ, Tutikian BF, da Boit K, Teixeira EC, Cabello JJ, Agudelo-Castañeda DM and Silva LFO: Coal emissions adverse human health effects associated with ultrafine/nano-particles role and resultant engineering controls. Environ Res. 158:450–455. 2017. View Article : Google Scholar : PubMed/NCBI
4	Shao H, Mohammed MU, Thomas N, Babazadeh S, Yang S, Shi Q and Shi L: Evaluating excessive burden of depression on health status and health care utilization among patients with hypertension in a nationally representative sample from the medical expenditure panel survey (MEPS 2012). J Nerv Ment Dis. 205:397–404. 2017. View Article : Google Scholar : PubMed/NCBI
5	Hsin YH, Chen CF, Huang S, Shih TS, Lai PS and Chueh PJ: The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett. 179:130–139. 2008. View Article : Google Scholar : PubMed/NCBI
6	Miller M, Raftis JB, Langrish JP, McLean SG, Samutrtai P, Connell SP, Wilson S, Vesey AT, Fokkens PHB, Boere AJF, et al: Inhaled nanoparticles accumulate at sites of vascular disease. Acs Nano. 11:4542–4552. 2017. View Article : Google Scholar : PubMed/NCBI
7	Kong L, Tang M, Zhang T, Wang D, Hu K, Lu W, Wei C, Liang G and Pu Y: Nickel nanoparticles exposure and reproductive toxicity in healthy adult rats. Int J Mol Sci. 15:21253–21269. 2014. View Article : Google Scholar : PubMed/NCBI
8	Xia T, Kovochich M and Nel AE: Impairment of mitochondrial function by particulate matter (PM) and their toxic components: Implications for PM-induced cardiovascular and lung disease. Front Biosci. 12:1238–1246. 2007. View Article : Google Scholar
9	Miao AJ, Schwehr KA, Xu C, Zhang SJ, Luo Z, Quigg A and Santschi PH: The algal toxicity of silver engineered nanoparticles and detoxification by exopolymeric substances. Environ Pollut. 157:3034–3041. 2009. View Article : Google Scholar : PubMed/NCBI
10	Geiser M, Rothen-Rutishauser B, Kapp N, Schürch S, Kreyling W, Schulz H, Semmler M, Im Hof V, Heyder J and Gehr P: Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells. Environ Health Perspect. 113:1555–1560. 2005. View Article : Google Scholar : PubMed/NCBI
11	Renwick LC, Donaldson K and Clouter A: Impairment of alveolar macrophage phagocytosis by ultrafine particles. Toxicol Appl Pharmacol. 172:119–127. 2001. View Article : Google Scholar : PubMed/NCBI
12	Lanone S and Boczkowski J: Biomedical applications and potential health risks of nanomaterials: Molecular mechanisms. Curr Mol Med. 6:651–663. 2006. View Article : Google Scholar : PubMed/NCBI
13	Nan A, Bai X, Son SJ, Lee SB and Ghandehari H: Cellular uptake and cytotoxicity of silica nanotubes. Nano Lett. 8:2150–2154. 2008. View Article : Google Scholar : PubMed/NCBI
14	Jia G, Wang H, Yan L, Wang X, Pei R, Yan T, Zhao Y and Guo X: Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environ Sci Technol. 39:1378–1383. 2005. View Article : Google Scholar : PubMed/NCBI
15	Nagano T, Nagano K, Nabeshi H, Yoshida T, Kamada H, Tsunoda SI, Gao JQ, Higashisaka K, Yoshioka Y and Tsutsumi Y: Modifying the surface of silica nanoparticles with amino or carboxyl groups decreases their cytotoxicity to parenchymal hepatocytes. Biol Pharm Bull. 40:726–728. 2017. View Article : Google Scholar : PubMed/NCBI
16	Duan J, Yu Y, Li Y, Liu H, Jing L, Yang M, Wang J, Li C and Sun Z: Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos. Nanotoxicology. 10:575–585. 2016. View Article : Google Scholar
17	Duan J, Hu H, Li Q, Jiang L, Zou Y, Wang Y and Sun Z: Combined toxicity of silica nanoparticles and methylmercury on cardiovascular system in zebrafish (Danio rerio) embryos. Environ Toxicol Pharmacol. 44:120–127. 2016. View Article : Google Scholar : PubMed/NCBI
18	Guerrero-Beltrán CE, Bernal-Ramírez J, Lozano O, Oropeza-Almazán Y, Castillo EC, Garza JR, García N, Vela J, García-García A, Ortega E, et al: Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca2+ handling in adult rat cardiomyocytes. Am J Physiol Heart Circ Physiol. 312:H645–H661. 2017. View Article : Google Scholar :
19	Duan J, Yu Y, Li Y, Huang P, Zhou X, Peng S and Sun Z: Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis. Part Fibre Toxicol. 11:502014. View Article : Google Scholar : PubMed/NCBI
20	Kreyling WG, Semmler-Behnke M, Takenaka S and Moller W: Differences in the biokinetics of inhaled nano-versus micrometer-sized particles. Acc Chem Res. 46:714–722. 2013. View Article : Google Scholar
21	Terzano C, Di Stefano F, Conti V, Graziani E and Petroianni A: Air pollution ultrafine particles: Toxicity beyond the lung. Eur Rev Med Pharmacol Sci. 14:809–821. 2010.
22	Geiser M: Update on macrophage clearance of inhaled micro- and nanoparticles. J Aerosol Med Pulm Drug Deliv. 23:207–217. 2010. View Article : Google Scholar : PubMed/NCBI
23	Semmler-Behnke M, Takenaka S, Fertsch S, Wenk A, Seitz J, Mayer P, Oberdörster G and Kreyling WG: Efficient elimination of inhaled nanoparticles from the alveolar region: Evidence for interstitial uptake and subsequent reentrainment onto airways epithelium. Environ Health Perspect. 115:728–733. 2007. View Article : Google Scholar : PubMed/NCBI
24	Zanobetti A and Schwartz J: The effect of particulate air pollution on emergency admissions for myocardial infarction: A multicity case-crossover analysis. Environ Health Perspect. 113:978–982. 2005. View Article : Google Scholar : PubMed/NCBI
25	Sullivan J, Sheppard L, Schreuder A, Ishikawa N, Siscovick D and Kaufman J: Relation between short-term fine-particulate matter exposure and onset of myocardial infarction. Epidemiology. 16:41–48. 2005. View Article : Google Scholar
26	Karacalioglu O, Arslan Z, Kilic S, Öztürk E and Ozguven M: Baseline serum levels of cardiac biomarkers in patients with stable coronary artery disease. Biomarkers. 12:533–540. 2007. View Article : Google Scholar : PubMed/NCBI
27	Salakou S, Kardamakis D, Tsamandas AC, Zolota V, Apostolakis E, Tzelepi V, Papathanasopoulos P, Bonikos DS, Papapetropoulos T, Petsas T and Dougenis D: Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. In Vivo. 21:123–132. 2007.PubMed/NCBI
28	Jiang W, Chen Y, Li B and Gao S: DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in the rat hippocampus. Mol Biosyst. 13:1863–1873. 2017. View Article : Google Scholar : PubMed/NCBI
29	Zhang Y, Yu W, Jiang X, Lv K, Sun S and Zhang F: Analysis of the cytotoxicity of differentially sized titanium dioxide nanoparticles in murine MC3T3-E1 preosteoblasts. J Mater Sci Mater Med. 22:1933–1945. 2011. View Article : Google Scholar : PubMed/NCBI
30	Kaiser JP, Wick P, Manser P, Spohn P and Bruinink A: Single walled carbon nanotubes (SWCNT) affect cell physiology and cell architecture. J Mater Sci Mater Med. 19:1523–1537. 2008. View Article : Google Scholar
31	Xu Z, Zhang YL, Song C, Wu LL and Gao HW: Interactions of hydroxyapatite with proteins and its toxicological effect to zebrafish embryos development. PLoS One. 7:e328182012. View Article : Google Scholar : PubMed/NCBI
32	Delfino RJ, Sioutas C and Malik S: Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ Health Perspect. 113:934–946. 2005. View Article : Google Scholar : PubMed/NCBI
33	Du Z, Zhao D, Jing L, Cui G, Jin M, Li Y, Liu X, Liu Y, Du H, Guo C, et al: Cardiovascular toxicity of different sizes amorphous silica nanoparticles in rats after intratracheal instillation. Cardiovasc Toxicol. 13:194–207. 2013. View Article : Google Scholar : PubMed/NCBI
34	Bai R, Zhang L, Liu Y, Meng L, Wang L, Wu Y, Li W, Ge C, Le Guyader L and Chen C: Pulmonary responses to printer toner particles in mice after intratracheal instillation. Toxicol Lett. 199:288–300. 2010. View Article : Google Scholar : PubMed/NCBI
35	Sweet MJ, Chessher A and Singleton I: Chapter five-review: Metal-based nanoparticles; size, function, and areas for advancement in applied microbiology. Adv Appl Microbiol. 80:113–142. 2012. View Article : Google Scholar
36	Böhme U and Scheler U: Hydrodynamic size and charge of polyelectrolyte complexes. J Phys Chem B. 111:8348–8350. 2007. View Article : Google Scholar : PubMed/NCBI
37	Oberdörster G, Oberdörster E and Oberdörster J: Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 113:823–839. 2005. View Article : Google Scholar : PubMed/NCBI
38	Chen Z, Meng H, Xing G, Yuan H, Zhao F, Liu R, Chang X, Gao X, Wang T, Jia G, et al: Age-related differences in pulmonary and cardiovascular responses to SiO2 nanoparticle inhalation: Nanotoxicity has susceptible population. Environ Sci Technol. 42:8985–8992. 2008. View Article : Google Scholar
39	Mor r is AS, Ad a mca kova-Dodd A, L eh ma n SE, Wongrakpanich A, Thorne PS, Larsen SC and Salem AK: Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs. Toxicol Lett. 241:207–215. 2016. View Article : Google Scholar
40	Kim JH, Kim CS, Ignacio RM, Kim DH, Sajo ME, Maeng EH, Qi XF, Park SE, Kim YR, Kim MK, et al: Immunotoxicity of silicon dioxide nanoparticles with different sizes and electrostatic charge. Int J Nanomedicine. 9(Suppl 2): 183–193. 2014. View Article : Google Scholar
41	Aravamudan B, Thompson M, Sieck GC, Vassallo R, Pabelick CM and Prakash YS: Functional effects of cigarette smoke-induced changes in airway smooth muscle mitochondrial morphology. J Cell Physiol. 232:1053–1068. 2016. View Article : Google Scholar : PubMed/NCBI
42	Li J, Lee B and Lee AS: Endoplasmic reticulum stress-induced apoptosis: Multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem. 281:7260–7270. 2006. View Article : Google Scholar : PubMed/NCBI
43	Satoh M, Matter CM, Ogita H, Takeshita K, Wang CY, Dorn GW II and Liao JK: Inhibition of apoptosis-regulated signaling kinase-1 and prevention of congestive heart failure by estrogen. Circulation. 115:3197–3204. 2007. View Article : Google Scholar : PubMed/NCBI
44	Murphy AN: Potential mechanisms of mitochondrial cytochrome-C release during apoptosis. Drug Dev Res. 46:18–25. 1999. View Article : Google Scholar
45	Wang Z, Lin D, Zhang L, Liu W, Tan H and Ma J: Penehyclidine hydrochloride prevents anoxia/reoxygenation injury and induces H9c2 cardiomyocyte apoptosis via a mitochondrial pathway. Eur J Pharmacol. 797:115–123. 2017. View Article : Google Scholar : PubMed/NCBI
46	Del Principe MI, Dal Bo M, Bittolo T, Buccisano F, Rossi FM, Zucchetto A, Rossi D, Bomben R, Maurillo L, Cefalo M, et al: Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia. Haematologica. 101:77–85. 2016. View Article : Google Scholar :
47	Marks N, Berg MJ, Guidotti A and Saito M: Activation of caspase-3 and apoptosis in cerebellar granule cells. J Neurosci Res. 52:334–341. 1998. View Article : Google Scholar : PubMed/NCBI
48	Julien O and Wells JA: Caspases and their substrates. Cell Death Differ. 24:1380–1389. 2017. View Article : Google Scholar : PubMed/NCBI
49	Shafagh M, Rahmani F and Delirezh N: CuO nanoparticles induce cytotoxicity and apoptosis in human K562 cancer cell line via mitochondrial pathway, through reactive oxygen species and P53. Iran J Basic Med Sci. 18:993–1000. 2015.
50	Al-Qubaisi MS, Rasedee A, Flaifel MH, Ahmad SH, Hussein-Al-Ali S, Hussein MZ, Zainal Z, Alhassan FH, Taufiq-Yap YH, Eid EE, et al: Induction of apoptosis in cancer cells by NiZn ferrite nanoparticles through mitochondrial cytochrome C release. Int J Nanomedicine. 8:4115–4129. 2013. View Article : Google Scholar : PubMed/NCBI
51	Sharma V, Anderson D and Dhawan A: Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis. 17:852–870. 2012. View Article : Google Scholar : PubMed/NCBI
52	Sun L, Li Y, Liu X, Jin M, Zhang L, Du Z, Guo C, Huang P and Sun Z: Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol In Vitro. 25:1619–1629. 2011. View Article : Google Scholar : PubMed/NCBI