Abstract
Recent attention has been focused on reproductive toxicity of nanoscale materials in combination with pre-existing environmental pollutants. Due to its unique characteristics, bismuth (III) oxide (Bi2O3) nanoparticles (BONPs) are being used in diverse fields including cosmetics and biomedicine. Benzo[a]pyrene (BaP) is a known endocrine disruptor that most common sources of BaP exposure to humans are cigarette smoke and well-cooked barbecued meat. Hence, joint exposure of BONPs and BaP in humans is common. There is scarcity of information on toxicity of BONPs in combination with BaP in human reproductive system. In this work, combined effects of BONPs and BaP in mouse spermatogonia (GC-1 spg) cells were assessed. Results showed that combined exposure of BONPs and BaP synergistically induced cell viability reduction, lactate dehydrogenase leakage, induction of caspases (-3 and -9) and mitochondrial membrane potential loss in GC-1 spg cells. Co-exposure of BONPs and BaP also synergistically induced production of pro-oxidants (reactive oxygen species and hydrogen peroxide) and reduction of antioxidants (glutathione and several antioxidant enzymes). Experiments with N-acetyl-cysteine (NAC, a reactive oxygen species scavenger) indicated that oxidative stress was a plausible mechanism of synergistic toxicity of BONPs and BaP in GC-1 spg cells. Present data could be helpful for future in vivo research and risk assessment of human reproductive system co-exposed to BONPs and BaP.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- Bi2O3 :
-
bismuth (III) oxide
- BONPs:
-
Bi2O3 nanoparticles
- GC-1 spg:
-
mouse spermatogonia cells
- BaP:
-
benzo[a]pyrene
- PAHs:
-
polycyclic aromatic hydrocarbons
- PXRD:
-
powder X-ray diffraction
- FETEM:
-
field emission transmission electron microscopy
- DLS:
-
dynamic light scattering
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- ATCC:
-
American Type Culture Collection
- FBS:
-
foetal bovine serum
- PC:
-
positive control
- MTT:
-
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
- H2DCFDA:
-
2′-7′-dichlorodihydrofluorescein diacetate
- LDH:
-
lactate dehydrogenase
- NAC:
-
N-acetyl-cysteine
- ROS:
-
reactive oxygen species
- H2O2 :
-
hydrogen peroxide
- MDA:
-
malondialdehyde
- LPO:
-
lipid peroxidation
- GSH:
-
glutathione
- GPx:
-
glutathione peroxidase
- SOD:
-
superoxide dismutase
- CAT:
-
catalase
- PCR:
-
polymerase chain reaction
- Rh-123:
-
Rhodamine-123
- MMP:
-
mitochondrial membrane potential
- ANOVA:
-
one-way analysis of variance
- μ:
-
microgram
- μM:
-
micromole
- DNA: TiO2 :
-
titanium dioxide, deoxyribonucleic acid
- TBT:
-
tributyltin
- BPA:
-
bisphenol A
- BDE:
-
decabromodiphenyl ether-209
- Cd:
-
cadmium
References
Abidin SZ, Zulkifli ZA, Razak KA, et al (2019) PEG coated bismuth oxide nanorods induced radiosensitization on MCF-7 breast cancer cells under irradiation of megavoltage radiotherapy beams. In: Materials Today: Proceedings. Elsevier Ltd, pp 1640–1645
Abudayyak M, Öztaş E, Arici M, Özhan G (2017) Investigation of the toxicity of bismuth oxide nanoparticles in various cell lines. Chemosphere 169:117–123. https://doi.org/10.1016/j.chemosphere.2016.11.018
Ahamed M, Akhtar MJ, Siddiqui MA, Ahmad J, Musarrat J, al-Khedhairy AA, AlSalhi MS, Alrokayan SA (2011) Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. Toxicology 283:101–108. https://doi.org/10.1016/j.tox.2011.02.010
Ahamed M, Akhtar MJ, Khan MAM, Alhadlaq HA, Alshamsan A (2016) Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2). Colloids Surfaces B Biointerfaces 148:665–673. https://doi.org/10.1016/j.colsurfb.2016.09.047
Ahamed M, Akhtar MJ, Khan MAM, Alhadlaq HA, Aldalbahi A (2017a) Nanocubes of indium oxide induce cytotoxicity and apoptosis through oxidative stress in human lung epithelial cells. Colloids Surfaces B Biointerfaces 156:157–164. https://doi.org/10.1016/j.colsurfb.2017.05.020
Ahamed M, Khan MAM, Akhtar MJ, Alhadlaq HA, Alshamsan A (2017b) Ag-do** regulates the cytotoxicity of TiO2 nanoparticles via oxidative stress in human cancer cells. Sci Rep 7:1–14. https://doi.org/10.1038/s41598-017-17559-9
Ahamed M, Akhtar MJ, Khan MAM, Alrokayan SA, Alhadlaq HA (2019) Oxidative stress mediated cytotoxicity and apoptosis response of bismuth oxide (Bi2O3) nanoparticles in human breast cancer (MCF-7) cells. Chemosphere 216:823–831. https://doi.org/10.1016/j.chemosphere.2018.10.214
Akhtar MJ, Ahamed M, Alhadlaq HA, Kumar S, Alrokayan SA (2020) Mitochondrial dysfunction, autophagy stimulation and non-apoptotic cell death caused by nitric oxide-inducing Pt-coated Au nanoparticle in human lung carcinoma cells. Biochim Biophys Acta - Gen Subj 1864:129452. https://doi.org/10.1016/j.bbagen.2019.129452
Al-Daghri NM, Alokail MS, Abd-Alrahman SH, Draz HM (2014) Polycyclic aromatic hydrocarbon distribution in serum of Saudi children using HPLC-FLD: marker elevations in children with asthma. Environ Sci Pollut Res Int 21:12085–12090. https://doi.org/10.1007/s11356-014-3108-0
Asweto CO, Hu H, Liang S, Wang L, Liu M, Yang H, Duan J, Sun Z (2018) Gene profiles to characterize the combined toxicity induced by low level co-exposure of silica nanoparticles and benzo[a]pyrene using whole genome microarrays in zebrafish embryos. Ecotoxicol Environ Saf 163:47–55. https://doi.org/10.1016/j.ecoenv.2018.07.059
Azari MR, Mohammadian Y, Pourahmad J, Khodagholi F, Mehrabi Y (2020) Additive toxicity of co-exposure to pristine multi-walled carbon nanotubes and benzo α pyrene in lung cells. Environ Res 183:109219. https://doi.org/10.1016/j.envres.2020.109219
Balakireva A V., Zamyatnin AA (2019) Cutting out the gaps between proteases and programmed cell death. Front Plant Sci 10:. https://doi.org/10.3389/fpls.2019.00704
Bogusz K, Tehei M, Stewart C, McDonald M, Cardillo D, Lerch M, Corde S, Rosenfeld A, Liu HK, Konstantinov K (2014) Synthesis of potential theranostic system consisting of methotrexate-immobilized (3-aminopropyl)trimethoxysilane coated α-Bi 2O3 nanoparticles for cancer treatment. RSC Adv 4:24412–24419. https://doi.org/10.1039/c4ra02160f
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1016/0003-2697(76)90527-3
Braydich-Stolle LK, Lucas B, Schrand A, Murdock RC, Lee T, Schlager JJ, Hussain SM, Hofmann M-C (2010) Silver nanoparticles disrupt GDNF/Fyn kinase signaling in spermatogonial stem cells. Toxicol Sci 116:577–589. https://doi.org/10.1093/toxsci/kfq148
Brohi RD, Wang L, Talpur HS, Wu D, Khan FA, Bhattarai D, Rehman ZU, Farmanullah F, Huo LJ (2017) Toxicity of nanoparticles on the reproductive system in animal models: a review. Front. Pharmacol. 8:606
Carré J, Gatimel N, Moreau J et al (2017) Does air pollution play a role in infertility?: a systematic review. Environ. Heal. A Glob. Access Sci. Source 16:82
Chang SY, Lee MY, Chung PS, Kim S, Choi B, Suh MW, Rhee CK, Jung JY (2019) Enhanced mitochondrial membrane potential and ATP synthesis by photobiomodulation increases viability of the auditory cell line after gentamicin-induced intrinsic apoptosis. Sci Rep 9:. https://doi.org/10.1038/s41598-019-55711-9
Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48:749–762
De Nicola M, Ghibelli L (2014) Glutathione depletion in survival and apoptotic pathways. Front Pharmacol 5. https://doi.org/10.3389/fphar.2014.00267
Deng R, Lin D, Zhu L, Majumdar S, White JC, Gardea-Torresdey JL, **ng B (2017) Nanoparticle interactions with co-existing contaminants: joint toxicity, bioaccumulation and risk. Nanotoxicology 11:591–612
Dhasmana A, Sajid Jamal QM, Mir SS, Bhatt MLB, Rahman Q, Gupta R, Siddiqui MH, Lohani M (2014) Titanium dioxide nanoparticles as guardian against environmental carcinogen benzo[alpha]pyrene. PLoS One 9:e107068. https://doi.org/10.1371/journal.pone.0107068
Ding SN, Shan D, Xue HG, Cosnier S (2010) A promising biosensing-platform based on bismuth oxide polycrystalline-modified electrode: characterization and its application in development of amperometric glucose sensor. Bioelectrochemistry 79:218–222. https://doi.org/10.1016/j.bioelechem.2010.05.002
El-Batal AI, El-Sayyad GS, El-Ghamry A et al (2017) Melanin-gamma rays assistants for bismuth oxide nanoparticles synthesis at room temperature for enhancing antimicrobial, and photocatalytic activity. J Photochem Photobiol B Biol 173:120–139. https://doi.org/10.1016/j.jphotobiol.2017.05.030
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77. https://doi.org/10.1016/0003-9861(59)90090-6
Falchi L, Khalil WA, Hassan M, Marei WFA (2018) Perspectives of nanotechnology in male fertility and sperm function. Int. J. Vet. Sci. Med. 6:265–269
Fang Q, Shi Q, Guo Y, Hua J, Wang X, Zhou B (2016) Enhanced bioconcentration of Bisphenol A in the presence of nano-TiO2 can lead to adverse reproductive outcomes in zebrafish. Environ Sci Technol 50:1005–1013. https://doi.org/10.1021/acs.est.5b05024
Ferreira JLR, Lonné MN, França TA, Maximilla NR, Lugokenski TH, Costa PG, Fillmann G, Antunes Soares FA, de la Torre FR, Monserrat JM (2014) Co-exposure of the organic nanomaterial fullerene C60 with benzo[a]pyrene in Danio rerio (zebrafish) hepatocytes: evidence of toxicological interactions. Aquat Toxicol 147:76–83. https://doi.org/10.1016/j.aquatox.2013.12.007
Hauser R, Skakkebaek NE, Hass U, Toppari J, Juul A, Andersson AM, Kortenkamp A, Heindel JJ, Trasande L (2015) Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union. J Clin Endocrinol Metab 100:1267–1277. https://doi.org/10.1210/jc.2014-4325
Iavicoli I, Fontana L, Leso V, Bergamaschi (2013) The effects of nanomaterials as endocrine disruptors. Int J Mol Sci 14(8):16732–16801. https://doi.org/10.3390/ijms140816732
Jeng HA, Bocca SM (2013) Influence of exposure to benzo[a]pyrene on mice testicular germ cells during spermatogenesis. J Toxicol https://doi.org/10.1155/2013/387850, 2013, 1, 9
Jurewicz J, Dziewirska E, Radwan M, Hanke W (2018) Air pollution from natural and anthropic sources and male fertility. Reprod. Biol. Endocrinol. 16:109
Kazerouni N, Sinha R, Hsu CH, Greenberg A, Rothman N (2001) Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study. Food Chem Toxicol 39:423–436. https://doi.org/10.1016/S0278-6915(00)00158-7
Khan MAM, Khan W, Ahamed M, Alhazaa AN (2017) Microstructural properties and enhanced photocatalytic performance of Zn doped CeO2 nanocrystals. Sci Rep 7:1–11. https://doi.org/10.1038/s41598-017-11074-7
Kim SM, Lee HM, Hwang KA, Choi KC (2017) Benzo(a)pyrene induced cell cycle arrest and apoptosis in human choriocarcinoma cancer cells through reactive oxygen species-induced endoplasmic reticulum-stress pathway. Food Chem Toxicol 107:339–348. https://doi.org/10.1016/j.fct.2017.06.048
Kumari L, Lin JH, Ma YR (2007) Synthesis of bismuth oxide nanostructures by an oxidative metal vapour phase deposition technique. Nanotechnology 18:295605. https://doi.org/10.1088/0957-4484/18/29/295605
Li L, Sillanpää M, Schultz E (2017) Influence of titanium dioxide nanoparticles on cadmium and lead bioaccumulations and toxicities to Daphnia magna. J Nanoparticle Res 19:1–12. https://doi.org/10.1007/s11051-017-3916-5
Liman R (2013) Genotoxic effects of bismuth (III) oxide nanoparticles by allium and comet assay. Chemosphere 93:269–273. https://doi.org/10.1016/j.chemosphere.2013.04.076
Liu Y, Nie Y, Wang J, Wang J, Wang X, Chen S, Zhao G, Wu L, Xu A (2018) Mechanisms involved in the impact of engineered nanomaterials on the joint toxicity with environmental pollutants. Ecotoxicol Environ Saf 162:92–102. https://doi.org/10.1016/j.ecoenv.2018.06.079
Mohd Zainudin NH, Razak KA, Abidin SZ et al (2020) Influence of bismuth oxide nanoparticles on bystander effects in MCF-7 and hFOB 1.19 cells under 10 MV photon beam irradiation. Radiat Phys Chem 177:109143. https://doi.org/10.1016/j.radphyschem.2020.109143
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4
Neal MS, Zhu J, Foster WG (2008) Quantification of benzo[a]pyrene and other PAHs in the serum and follicular fluid of smokers versus non-smokers. Reprod Toxicol 25:100–106. https://doi.org/10.1016/j.reprotox.2007.10.012
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3
Periasamy AP, Yang S, Chen SM (2011) Preparation and characterization of bismuth oxide nanoparticles-multiwalled carbon nanotube composite for the development of horseradish peroxidase based H2O2 biosensor. Talanta 87:15–23. https://doi.org/10.1016/j.talanta.2011.09.021
Pinho AR, Martins F, Costa MEV, Senos AMR, da Cruz e Silva OAB, Pereira ML, Rebelo S (2020) In vitro cytotoxicity effects of zinc oxide nanoparticles on spermatogonia cells. Cells 9. https://doi.org/10.3390/cells9051081
Ramesh A, Kumar A, Aramandla MP, Nyanda AM (2015) Polycyclic aromatic hydrocarbon residues in serum samples of autopsied individuals from Tennessee. Int J Environ Res Public Health 12:322–334. https://doi.org/10.3390/ijerph120100322
Rotruck JT, Pope AL, Ganther HE et al (1973) Selenium: biochemical role as a component of glatathione peroxidase. Science (80- ) 179:588–590. https://doi.org/10.1126/science.179.4073.588
Shahbazi MA, Faghfouri L, Ferreira MPA, Figueiredo P, Maleki H, Sefat F, Hirvonen J, Santos HA (2020) The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative properties. Chem. Soc. Rev. 49:1253–1321
Siddiqui MA, Alhadlaq HA, Ahmad J, al-Khedhairy AA, Musarrat J, Ahamed M (2013) Copper oxide nanoparticles induced mitochondria mediated apoptosis in human hepatocarcinoma cells. PLoS One 8: https://doi.org/10.1371/journal.pone.0069534
Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394. https://doi.org/10.1016/0003-2697(72)90132-7
Solanki PR, Singh J, Rupavali B, Tiwari S, Malhotra BD (2017) Bismuth oxide nanorods based immunosensor for mycotoxin detection. Mater Sci Eng C 70:564–571. https://doi.org/10.1016/j.msec.2016.09.027
Sun D, Chen Q, Zhu B, Lan Y, Duan S (2020) Long-term exposure to benzo[a]pyrene affects sexual differentiation and embryos toxicity in three generations of marine Medaka (Oryzias melastigma). Int J Environ Res Public Health 17:970. https://doi.org/10.3390/ijerph17030970
Verhofstad N, van Oostrom CTM, Zwart E, Maas LM, van Benthem J, van Schooten FJ, van Steeg H, Godschalk RWL (2011) Evaluation of benzo(a)pyrene-induced gene mutations in male germ cells. Toxicol Sci 119:218–223. https://doi.org/10.1093/toxsci/kfq325
Wang J, Yang X, Zhao K, Xu P, Zong L, Yu R, Wang D, Deng J, Chen J, **ng X (2013) Precursor-induced fabrication of β-Bi2O3 microspheres and their performance as visible-light-driven photocatalysts. J Mater Chem A 1:9069–9074. https://doi.org/10.1039/c3ta11652b
Wang Q, Chen Q, Zhou P, Li W, Wang J, Huang C, Wang X, Lin K, Zhou B (2014) Bioconcentration and metabolism of BDE-209 in the presence of titanium dioxide nanoparticles and impact on the thyroid endocrine system and neuronal development in zebrafish larvae. Nanotoxicology 8:196–207. https://doi.org/10.3109/17435390.2013.875232
Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L (2018) Potential adverse effects of nanoparticles on the reproductive system. Int J Nanomedicine 13:8487–8506. https://doi.org/10.2147/IJN.S170723
Wang S, Ren X, Hu X, Zhou L, Zhang C, Zhang M (2019) Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells, a model of mouse Leydig cells. Toxicol Appl Pharmacol 368:37–48. https://doi.org/10.1016/j.taap.2019.02.012
Wang Z, Yang P, **e J, Lin HP, Kumagai K, Harkema J, Yang C (2020) Arsenic and benzo[a]pyrene co-exposure acts synergistically in inducing cancer stem cell-like property and tumorigenesis by epigenetically down-regulating SOCS3 expression. Environ Int 137:105560. https://doi.org/10.1016/j.envint.2020.105560
Yang W-W, Miao A-J, Yang L-Y (2012) Cd2+ Toxicity to a green alga Chlamydomonas reinhardtii as influenced by its adsorption on TiO2 engineered nanoparticles. PLoS One 7:e32300. https://doi.org/10.1371/journal.pone.0032300
Yang D, Zhang M, Gan Y, Yang S, Wang J, Yu M, Wei J, Chen J (2020) Involvement of oxidative stress in ZnO NPs-induced apoptosis and autophagy of mouse GC-1 spg cells. Ecotoxicol Environ Saf 202:110960. https://doi.org/10.1016/j.ecoenv.2020.110960
Zhu X, Zhou J, Cai Z (2011) TiO2 nanoparticles in the marine environment: impact on the toxicity of tributyltin to abalone (Haliotis diversicolor supertexta) embryos. Environ Sci Technol 45:3753–3758. https://doi.org/10.1021/es103779h
Zulkifli ZA, Razak KA, Rahman WNWA, Abidin SZ (2018) Synthesis and characterisation of bismuth oxide nanoparticles using hydrothermal method: the effect of reactant concentrations and application in radiotherapy. In: Journal of Physics: Conference Series. Institute of Physics Publishing, p 12103
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The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group no. RG- 1439-072.
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Maqusood Ahamed: conceptualisation, data curation, formal analysis, funding acquisition, investigation; supervision, writing—original draft, writing—review and editing. Mohd Javed Akhtar: investigation, methodology, software. M.A. Majeed Khan: data curation, formal analysis, methodology. Hisham A. Alhadlaq: formal analysis, resources, software.
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Ahamed, M., Akhtar, M.J., Khan, M.A.M. et al. Co-exposure of Bi2O3 nanoparticles and bezo[a]pyrene-enhanced in vitro cytotoxicity of mouse spermatogonia cells. Environ Sci Pollut Res 28, 17109–17118 (2021). https://doi.org/10.1007/s11356-020-12128-6
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DOI: https://doi.org/10.1007/s11356-020-12128-6