Between-strain differences in hypothermic response in mice after intranasal administration of PtO nanoparticles. D. V. Petrovskii, A. V. Romashchenko, S. Yu. Troitskii, M. P. Moshkin


Air pollution by particulate matter (PM) has been associated with cardiopulmonary morbidity and mortality in many recent epidemiological studies. It has been shown that transition metal compounds, well- known toxic components of PM, are able to induce hypothermia following whole-body inhalation exposure. Low temperature appears to protect tissue against toxic effects of PM metal compounds in vivo and in vitro. To study the role of soluble and insoluble irritants in the induction of the hypothermic response, we analyz­ed the decrease in mouse body temperature (Δtbody) after intranasal administration of PtO nanoparticles or a K2[PtCl 4] solution. Between-strain differences in Δtbody after intranasal administration of the irritants were evaluated using 6 inbred (BALB/cJ, C57BL/6J, AKR/OlaHsd, DBA/2JRccHsd, C3H/HeNHsd, and SJL/J) and 2 outbred mouse strains (SCID and CD1). BALB/cJ and SCID mice showed the most pronounced effect of intranasal admini­stration of the xenobiotic on tbody. Thus, tbody was signi­ficantly lower after nasal administration the PtO nano­particles than after administration of the K2[PtCl 4] solution. To study the mechanism of this decrease, we compar­ed the respective values for Δtbody following intra­nasal, intravenous and peroral administration of PtO nanoparticles in Balb/c mice. Neither intravenous nor peroral administration had any effect on mouse body temperature. This fact together with data on the dynamics of the decrease in mouse body temperature following intranasal administration of PtO nanoparticles (max Δtbody ~ 80–100 min) allowed us to assume that this process is under nervous regulation. The correlation found between our data and some well-known phenotypic characteristics ( of the mouse strains used confirms this hypothesis.

About The Authors:

D. V. Petrovskii. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. V. Romashchenko. Institute of Cytology and Genetics SB RAS; Design Technological Institute of Digital Technique SB RAS, Russian Federation, Novosibirsk

S. Yu. Troitskii. Boreskov Institute of Catalysis SB RAS, Russian Federation, Novosibirsk

M. P. Moshkin. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk


1. Aoki Y., Sato H., Nishimura N., Takahashi S., Itoh K., Yamamoto M. Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol. Appl. Pharm. 2001;173(3):154-160.

2. Becerra L., Morris S., Bazes S., Gostic R., Sherman S., Gostic J., Pendse G., Moulton E., Scrivani S., Keith D., Chizh B., Borsook D. Trigeminal neuropathic pain alters responses in CNS circuits to mechanical (brush) and thermal (cold and heat) stimuli. J. Neurosci. 2006;26(42):10646-10657.

3. Brook R.D., Rajagopalan S., Pope C.A. 3rd, Brook J.R., Bhatnagar A., Diez-Roux A.V., Holguin F., Hong Y., Luepker R.V., Mittleman M.A., Peters A., Siscovick D., Smith S.C. Jr, Whitsel L., Kaufman J.D. Particulate matter air pollution and cardiovascular disease an update to the scientific statement from the American Heart Association. Circulation. 2010;121(21):2331-2378.

4. Bryant B.P., Moore P.A. Factors affecting the sensitivity of the lingual trigeminal nerve to acids. Am. J. Physiol.-Reg. Integr. Compar. Physiol. 1995;268(1):R58-R65.

5. Burnett R.T., Dales R., Krewski D., Vincent R., Dann T., Brook J.R. Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases. Am. J. Epidemiol. 1995;142(1):15-22.

6. Campen M.J., Nolan J.P., Schladweiler M.C.J., Kodavanti U.P., Evansky P.A. Costa D.L., Watkinson W.P. Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: a potential interaction between nickel and vanadium sulfate. Toxicol. Sci. 2001;64(2):243-252.

7. Diociaiuti M., Balduzzi M., De Berardis B., Cattani G., Stacchini G., Ziemacki G., Marconi A., Paoletti L. The two PM 2.5 (fine) and PM 2.5-10 (coarse) fractions: evidence of different biological activity. Environ. Res. 2001;86(3):254-262.

8. Dockery D.W., Pope C.A. Acute respiratory effects of particulate air pollution. Annu. Rev. Publ. Health. 1994;15(1):107-132.

9. Dreher K.L., Jaskot R.H., Lehmann J.R., Richards J.H., McGee J.K., Ghio A.J., Costa D.L. Soluble transition metals mediate residual oil fly ash induced acute lung injury. J. Toxicol. Environ. Health. 1997;50(3):285-305.

10. Dye J.A., Adler K.B., Richards J.H., Dreher K.L. Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression. Am. J. Physiol.-Lung Cell. Mol. Physiol. 1999;277(3): L498-L510.

11. Georgieva M., Andonovski B. Determination of platinum (IV) by UV spectrophotometry. Analyt. Bioanalyt. Chem. 2003;375(6):836-839.

12. Gordon C.J. Toxic-induced hypothermia and hypometabolism: Do they increase uncertainty in the extrapolation of toxicological data from experimental animals to humans? Neurosci. Biobehav. Rev. 1991;15(1):95-98.

13. Han J.Y., Takeshita K., Utsumi H. Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles. Free Radical Biol. Med. 2001;30(5):516-525.

14. Hayama T. Thermoreceptive neurons in the dorsal portion of the trigeminal principal nucleus in rats. Neurosci. Lett. 2014;564:53-56.

15. Hayashi T., Cottam H.B., Chan M., Jin G., Tawatao R.I., Crain B., Ronacher L., Messer K., Carson D.A., Corr M. Mast cell-dependent anorexia and hypothermia induced by mucosal activation of Toll-like receptor 7. Am. J. Physiol.-Reg, Integr. Compar. Physiol. 2008;295(1):R123-R132.

16. Kodavanti U.P., Jackson M.C., Ledbetter A.D., Richards J.R., Gardner S.Y., Watkinson W.P., Campen M.J., Costa D.L. Lung injury from intratracheal and inhalation exposures to residual oil fly ash in a rat model of monocrotaline-induced pulmonary hypertension. J. Toxicol. Environ. Health. 1999;57(8):543-563.

17. Komai M., Bryant B.P. Acetazolamide specifically inhibits lingual trigeminal nerve responses to carbon dioxide. Brain Res. 1993;612(1): 122-129.

18. McCormick D.A., Bal T. Sensory gating mechanisms of the thalamus. Curr. Opin. Neurobiol. 1994;4(4):550-556.

19. Mills N.L., Törnqvist H., Robinson S.D., Gonzalez M., Darnley K., MacNee W., Boon N.A., Donaldson K., Blomberg A., Sandstrom T., Newby D.E. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005;112(25): 3930-3936.

20. Moldovan M., Palacios M.A., Gómez M.M., Morrison G., Rauch S., McLeod C., Ma R., Caroli S., Alimonti A., Petrucci F., Bocca B., Schramel P., Zischka M., Pettersson C., Wass U., Luna M., Saenz J.C., Santamaría J. Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters. Sci. Total Environ. 2002;296(1): 199-208.

21. Morrison S.F., Nakamura K. Central neural pathways for thermoregulation. Frontiers Biosci. 2011;16:74.

22. Moshkin M.P., Peltek S.E., Gerlinskaya L.A., Goryachkovskaya T.N., Kontsevaya G.V., Maslennikova S.O., Popik V.V., Kolchanov N.A. Acute immune response to the intranasal application of nanoparticles of SiO2 (Tarkosil 25) in mice of two strains. Ros. nanotechnologii — Nanotechnologies in Russia. 2011;6(9/10):47-54.

23. Schins R.P., Polat D., Begerow J., Turfeld M., Becker A., Borm P.J.

24. Platinum levels in nasal lavage fluid as a biomarker for traffic-related exposure and inflammation in children. Sci. Total Environ. 2004;334:447-455.

25. Schwartz J., Morris R. Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. Am. J. Epidemiol. 1995; 142(1):23-35.

26. Ulfvarson U., Alexandersson R., Dahlqvist M., Ekholm U., Bergström B. Pulmonary function in workers exposed to diesel exhausts: the effect of control measures. Am. J. Ind. Med. 1991;19(3):283-289.

27. Upadhyay J., Knudsen J., Anderson J., Becerra L., Borsook D. Noninvasive mapping of human trigeminal brainstem pathways. Magn. Reson. Med. 2008;60(5):1037-1046.

28. Watkinson W.P., Campen M.J., Nolan J.P., Costa D.L. Cardiovascular and systemic responses to inhaled pollutants in rodents: effects of ozone and particulate matter. Environ. Health Persp. 2001; 109(4):539.

29. Xiao G.G., Wang M., Li N., Loo J.A., Nel A.E. Use of proteomics to demonstrate a hierarchical oxidative stress response to diesel exhaust particle chemicals in a macrophage cell line. J. Biol. Chem. 2003;278(50):50781-50790.

30. Zhu H., Fan J., Xu Q., Li H., Wang J., Gao P., Peng X. Imaging of lysosomal pH changes with a fluorescent sensor containing a novel lysosome-locating group. Chem. Commun. 2012;48(96): 11766-11768.

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