DOI QR코드

DOI QR Code

Distribution of molybdenum in soft tissues and blood of rats after intratracheal instillation of molybdenum(IV) sulfide nano- and microparticles

  • Received : 2023.05.07
  • Accepted : 2023.09.26
  • Published : 2024.01.15

Abstract

There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg-1 b.w.) and higher (5 mg Mo kg-1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS2-NPs) and microparticles (MoS2-MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS2-MPs and MoS2-NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS2-NPs and MoS2-MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS2-NPs compared to MoS2-MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.

Keywords

Acknowledgement

The authors would like to thank K. Ranoszek-Soliwoda, G. Celichowski from the University of Lodz, (Department of Materials Technology and Chemistry, Faculty of Chemistry, Lodz, Poland) for the chemical synthesis of MoS2, as well as K. Sitarek, R. Swiercz, Z. Pisarek, B. Pawlak and K. Mader for their assistance during the animal experiments, and T. Podsiadly and W. Kuszka for the determination of Mo concentration in blood. Moreover, the authors would like to thank C. Derrick Quarles Jr. (Elemental Scientific, Inc.) and Charles Sisson (Applied Spectra, Inc.) for their valuable suggestions and excellent technical assistance during the training and optimization of the J200 Tandem LA/LIBS.

References

  1. Meng FM, Cui ZT, Cheng ZT, Han HL (2018) Experimental study on tribological properties of graphite-MoS2 coating on GCr15. J Tribol 140:051303. https://doi.org/10.1115/1.4039796
  2. Hou K, Han M, Liu X, Wang J, He Y, Yang S (2018) In situ formation of spherical MoS2 nanoparticles for ultra-low friction. Nanoscale 10:19979-19986. https://doi.org/10.1039/C8NR06503A
  3. Zhang Y, Li P, Li Ji L, Liu X, Wan H, Chen L, Li H, Jin Z (2021) Tribological properties of MoS2 coating for ultra-long wear-life and low coefficient of friction combined with additive g-C3N4 in air. Friction 9:789-801. https://doi.org/10.1007/s40544-020-0374-3
  4. Zan W, Geng W, Liu H, Yao X (2016) Electronic properties of MoS2 on monolayer, bilayer and bulk SiC: a density functional theory study. J Alloys Compd 666:204-208. https://doi.org/10.1016/j.jallcom.2016.01.108
  5. Shanmugavel R, Chinthakndi N, Selvam M, Madasamy N, Shanmugakani SK, Nair A, Prakash C, Buddhi D, Dixit S (2022) AlMg-MoS2 reinforced metal matrix composites: machinability characteristics. Materials 15:4548. https://doi.org/10.3390/ma15134548
  6. European Commission, Directorate-General for Environment (1999) Guidelines for setting specific concentration limits for carcinogens in Annex I of Directive 67/548/EEC: inclusion of potency considerations. Publications Office. https://op.europa.eu/en/publication-detail/-/publication/33b0ae1e-bba6-4fcc-8005-d137fdd76113. Accessed 24 Apr 2023
  7. Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 (Text with EEA relevance). https://eurlex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32008R1272. Accessed 24 Apr 2023
  8. Park MV, Neigh AM, Vermeulen JP, de la Fonteyne LJ, Verharen HW, Briede JJ, van Loveren H, de Jong WH (2011) The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials 32:9810-9817. https://doi.org/10.1016/j.biomaterials.2011.08.085
  9. Saraiva C, Praca C, Ferreira R, Santos T, Ferreira L, Bernardino L (2016) Nanoparticle-mediated brain drug delivery: overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 235:34-47. https://doi.org/10.1016/j.jconrel.2016.05.044
  10. Omarch G, Kippie Y, Mentor S, Ebrahim N, Fisher D, Murilla G, Swai H, Dube A (2019) Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes. Artif Cells Nanomed Biotechnol 47:1428-1436. https://doi.org/10.1080/21691401.2019.1596923
  11. Costa A, de Souza C-W, Seabra V, Sarmento B, Lehr CM (2019) Triple co-culture of human alveolar epithelium, endothelium and macrophages for studying the interaction of nanocarriers with the air-blood barrier. Acta Biomater 91:235-247. https://doi.org/10.1016/j.actbio.2019.04.037
  12. Tjalve H, Henriksson J, Tallkvist J, Larsson BS, Lindquist NG (1996) Uptake of manganese and cadmium from the nasal mucosa into the central nervous system via olfactory pathways in rats. Pharmacol Toxicol 79:347-356. https://doi.org/10.1111/j.1600-0773.1996.tb00021.x
  13. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437-445. https://doi.org/10.1080/08958370490439597
  14. Engin AB, Engin A (2019) Nanoparticles and neurotoxicity: dual response of glutamatergic receptors. Prog Brain Res 245:281-303. https://doi.org/10.1016/bs.pbr.2019.03.005
  15. Sobanska Z, Sitarek K, Gromadzinska J, Swiercz S, Szparaga M, Domeradzka-Gajda K, Kowalczyk K, Zapor L, Wasowicz W, Grobelny J, Ranoszek-Soliwoda K, Tomaszewsk E, Celichowski G, Roszak J, Stepnik M (2020) Assessment of acute toxicological effects of molybdenum(IV) disulfide nano- and microparticles after single intratracheal administration in rats. Sci Total Environ 742:140545. https://doi.org/10.1016/j.scitotenv.2020.140545
  16. Sorli JB, Jensen ACO, Mortensen A, Szarek J, Gutierrez CAT, Givelet L, Loeschner K, Loizides C, Hafez I, Biskos G, Vogel U, Hadrup N (2023) Pulmonary toxicity of molybdenum disulphide after inhalation in mice. Toxicol 485:153428. https://doi.org/10.1016/j.tox.2023.153428
  17. Pena NO, Cherukula K, Even B, Ji DK, Razafindrakoto S, Peng S, Silva AKA, Moyon CM, Hillaireau H, Bianco A, Fattal E, Alloyeau D, Gazeau F (2023) Resolution of MoS2 nanosheets-induced pulmonary inflammation driven by nanoscale intracellular transformation and extracellular-vesicle shuttles. Adv Mater 35:2209615. https://doi.org/10.1002/adma.202209615
  18. Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL (2006) Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci 91:227-236. https://doi.org/10.1093/toxsci/kf140
  19. Warheit DB, Webb TR, Colvin VL, Reed KL, Sayes CM (2007) Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol Sci 95:270-280. https://doi.org/10.1093/toxsci/kf128
  20. Ma-Hock L, Burkhardt S, Strauss V, Gamer AO, Wiench K, van Ravenzwaay B, Landsiedel R (2009) Development of a short-term inhalation test in the rat using nano-titanium dioxide as a model substance. Inhal Toxicol 21:102-118. https://doi.org/10.1080/08958370802361057
  21. Bailey MR, Ansoborlo E, Guilmette RA, Paquet F (2007) Updating the ICRP human respiratory tract model. Radiat Prot Dosimetry 127:31-34. https://doi.org/10.1093/rpd/ncm249
  22. ICRP (2012) Annals of the ICRP: Compendium of dose coefficients based on ICRP publication 60. International Commission on Radiological Protection. ICRP Publication 119. http://www.icrp.org/publication.asp?id=ICRP%20Publication%20119. Accessed 24 Apr 2023
  23. Agency for Toxic Substances and Disease Registry (ATSDR) (2020) Toxicological profle for Molybdenum. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA
  24. Fairhall LT, Dunn RC, Sharpless NE, Pritchard EA (1945) The toxicity of molybdenum. Public Health Bull 293(36):52
  25. National Toxicology Program (NTP) (1997) Toxicology and carcinogenesis studies of molybdenum trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies). Natl Toxicol Program Tech Rep Ser 462:1-269
  26. Werner E, Roth P, Heinrichs U, Giussani A, Cantone MC, Zilker TH, Felgenhauer N, Greim H (2000) Internal biokinetic behavior of molybdenum in humans studied with stable isotopes as tracers. Isotopes Environ Health Stud 36:123-132. https://doi.org/10.1080/10256010008032938
  27. Kuras R, Stepnik M, Domeradzka-Gajda K, Janasik B (2024) The use of LA-ICP-MS as an auxiliary tool to assess the pulmonary toxicity of molybdenum(IV) sulfide (MoS2) nano- and microparticles. IJOMEH 37. https://doi.org/10.13075/ijomeh.1896.02305
  28. Turnlund JR, Keyes WR (2004) Plasma molybdenum reflects dietary molybdenum intake. J Nutr Biochem 15:90-95. https://doi.org/10.1016/j.jnutbio.2003.10.003
  29. Novotny JA, Turnlund JR (2007) Molybdenum intake influences molybdenum kinetics in men. J Nutr 137:37-42. https://doi.org/10.1093/jn/137.1.37
  30. Engel RW, Price NO, Miller RF (1967) Copper, manganese, cobalt, and molybdenum balance in preadolescent girls. J Nutr 92:197-204. https://doi.org/10.1093/jn/92.2.197
  31. Schroeder HA, Balassa JJ, Tipton IH (1970) Essential trace metals in man: molybdenum. J Chronic Dis 23:481-499. https://doi.org/10.1016/0021-9681(70)90056-1
  32. Giussani A (2008) A recycling systemic model for the biokinetics of molybdenum radionuclides. Sci Total Environ 404:44-55. https://doi.org/10.1016/j.scitotenv.2008.06.019
  33. Bell MC, Diggs BG, Lowrey RS, Wright PL (1964) Comparison of Mo99 metabolism in swine and cattle as affected by stable molybdenum. J Nutr 84:367-372. https://doi.org/10.1093/jn/84.4.367
  34. Appel JH, Li DO, Podlevsky JD, Debate A, Green AA, Wang QH, Chae J (2016) Low cytotoxicity and genotoxicity of two-dimensional MoS2 and WS2. ACS Biomater Sci Eng 2:361-367. https://doi.org/10.1021/acsbiomaterials.5b00467
  35. Chng EL, Sofer Z, Pumera M (2014) MoS2 exhibits stronger toxicity with increased exfoliation. Nanoscale 6:14412-14418. https://doi.org/10.1039/C4NR04907A
  36. Chan PC, Herbert RA, Roycroft JH, Haseman JK, Grumbein SL, Miller RA, Chou BJ (1998) Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice. Toxicol Sci 45:58-65. https://doi.org/10.1006/toxs.1998.2497
  37. Huber EA, Cerreta JM (2022) Mechanisms of cell injury induced by inhaled molybdenum trioxide nanoparticles in Golden Syrian Hamsters. Exp Biol Med 247:2067-2080. https://doi.org/10.1177/15353702221104033
  38. Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975-983. https://doi.org/10.1016/j.tiv.2005.06.034
  39. Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann M-C (2005) In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 88:412-419. https://doi.org/10.1093/toxsci/kf256
  40. Wang X, Oberleas D, Yang MT, Yang SP (1992) Molybdenum requirement of female rats. J Nutr 122:1036-1041. https://doi.org/10.1093/jn/122.4.1036
  41. Yang MT, Yang SP (1989) Effiect of molybdenum supplementation on hepatic trace elements and enzymes of female rats. J Nutr 119:221-227. https://doi.org/10.1093/jn/119.2.221
  42. Arrington LR, Davis GK (1953) Molybdenum toxicity in the rabbit. J Nutr 51:295-304. https://doi.org/10.1093/jn/51.2.295
  43. Pandey R, Kumar R, Singh SP, Srivastava SP (2002) Molybdenum in rat tissue. Hum Exp Toxicol 21:33-35. https://doi.org/10.1191/0960327102ht203oa
  44. Kusum RR, Verma PK, Pankaj NK, Kant V, Kumar J, Srivastava AK (2010) Haematolohical profile of subacute oral toxicity of molybdenum and ameliorative efficacy of copper salt in goats. Toxicol Int 17:82-85. https://doi.org/10.4103/0971-6580.72676
  45. Lyubimov AV, Smith JA, Rousselle SD, Mercieca MD, Tomaszewski JE, Smith AC, Levine BS (2004) The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats. Reprod Toxicol 19:223-233. https://doi.org/10.1016/j.reprotox.2004.07.006
  46. Asadi F, Mohseni M, Dadashi Noshahr K, Soleymani FH, Jalilvand A, Heidari A (2017) Effect of molybdenum nanoparticles on blood cells, liver enzymes, and sexual hormones in male rats. Biol Trace Elem Res 175:50-56. https://doi.org/10.1007/s12011-016-0765-5