Skip to main content
Log in

Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 μg Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention in the lung tissue following IT instillation of NiSO4 was saturable with reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were evaluated by biochemical, elemental and cytological indicators in bronchoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Activities of lactate dehydrogenase and β-glucuronidase, contents of lysozyme, protein, sulfur and calcium, and the number of polymorphonuclear leukocytes were increased with a peak at 2–3 days post-instillation, while BALF alkaline phosphatase (ALP) activity was significantly decreased after IT instillation of NiSO4. Lung tissue ALP activity was also decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type II cells (a major source of BALF ALP). Thiobarbituric acid reacting substances in the lung tissue were not changed by NiSO4, suggesting that lipid peroxidation plays a minimal, if any role, in the Ni-induced inflammation in the rat lung.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adkins B, Eichard JH, Gardner DE (1979) Enhancement of experimental respiratory infection following nickel inhalation. Environ Res 20: 33–42

    Article  PubMed  CAS  Google Scholar 

  • Amanuma K, Suzuki KT (1987) Effect of intratracheal instilation of cadmium chloride on phospholipids in alveolar wash fluid. Toxicology 44: 321–328

    Article  PubMed  CAS  Google Scholar 

  • Basbaum CB, Finkbeiner WE (1989) Muscus-producing cells of the airways. In Massaro D (ed) Lung cell biology. Marcel Dekker, New York, pp 37–79

    Google Scholar 

  • Benson JM, Burt DG, Cheng YS, Hahn FF, Haley PJ, Henderson RF, Hobbs CH, Pickrell JA, Dunnick JK (1989) Biochemical responses of rat and mouse lungs to inhaled nickel compounds. Toxicology 57: 255–266

    Article  PubMed  CAS  Google Scholar 

  • Cursted T, Hagman M, Robertson B, Camner P (1983) Rabbit lungs after long-term exposure to low nickel dust concentration. Environ Res 30: 89–94

    Article  Google Scholar 

  • Donskoy E, Donskoy M, Forouhar F, Gillies CG, Marzouk A, Reid MC, Zaharia O, Sunderman FW Jr (1986) Hepatic toxicity of nickel chloride in rats. Ann Clin Lab Sci 16: 108–117

    PubMed  CAS  Google Scholar 

  • Dunnick JK, Benson JM, Hobbs CH, Hahn FF, Cheng Y, Eidson AF (1988) Comparative toxicity of nickel oxide, nickel sulfate hexahydrate, and nickel subsulfide after 12 days of inhalation exposure to F344/N rats and B6C3F1 mice. Toxicology 50: 145–156

    Article  PubMed  CAS  Google Scholar 

  • Dunnick JK, Elwell MR, Benson JM, Hobbs CH, Hahn FF, Haly PJ, Cheng YS, Eidson AF (1989) Lung toxicity after 13-week inhalation exposure to nickel oxide, nickel subsulfide, or nickel sulfate hexahydrate in F344/N rats and B6C3F1 mice. Fundam Appl Toxicol 12: 584–594

    Article  PubMed  CAS  Google Scholar 

  • Edelson JD, Shannon JM, Mason RJ (1988) Alkaline phosphatase; a marker of type II cell differentiation. Am Rev Respir Dis 138: 1268–1275

    PubMed  CAS  Google Scholar 

  • Ezawa I (1985) Metabolism of phosphorus and calcium in human. Jpn J Clin Dialysis 1: 739–745 (in Japanese)

    Google Scholar 

  • Forget G, Lacroix M-J, Calvert R, Sirois P (1984) Measurement of β-glucuronidase effluent of perfused alveolar macrophages challenged with chemically modified chrysotile asbestos. Inflammation 8: 123–141

    Article  PubMed  CAS  Google Scholar 

  • Henderson RF, Rebar AH, Pickrell JA, Newton GJ (1979) Early damage indicators in the lung. III. Biochemical and cytological response of the lung to inhaled metal salts. Toxicol Appl Pharmacol 50: 123–136

    Article  PubMed  CAS  Google Scholar 

  • Hirano S (1987a) A proportional method for the dilution of submicron hygroscopic aerosols. Am Ind Hyg Assoc J 48: 969–971

    CAS  Google Scholar 

  • Hirano S (1987b) Automatic control of aerosol concentration in exposure chambers. Am Ind Hyg Assoc J 48: 972–976

    CAS  Google Scholar 

  • Hirano S, Tsukamoto N, Kobayashi E, Suzuki KT (1989a) Toxicity of cadmium oxide instilled into the rat lung. I. Metabolism of cadmium oxide in the lung and its effects on essential elements. Toxicology 55: 15–24

    Article  PubMed  CAS  Google Scholar 

  • Hirano S, Higo S, Tsukamoto N, Kobayashi E, Suzuki KT (1989b) Pulmonary clearance and toxicity of zinc oxide instilled into the rat lung. Arch Toxicol 63: 336–342

    Article  PubMed  CAS  Google Scholar 

  • Hirano S, Sakai S, Ebihara H, Kodama N, Suzuki KT (1990a) Metabolism and pulmonary toxicity of intratracheally instilled cupric sulfate in rats. Toxicology 64: 223–233

    Article  PubMed  CAS  Google Scholar 

  • Hirano S, Kodama N, Shibata K, Suzuki KT (1990b) Distribution, localization, and pulmonary effects of yttrium chloride following intratracheal instillation into the rat. Toxicol Appl Pharmacol 104: 301–311

    Article  PubMed  CAS  Google Scholar 

  • Holzman RS, Gardner DE, Coffin DL (1968) In vivo inactivation of lysozyme by ozone. J Bacteriol 96: 1562–1566

    PubMed  CAS  Google Scholar 

  • Johansson A, Cammer P, Jarstrand C, Wiernik A (1980) Morphology and function of alveolar macrophages after long-term nickel exposure. Environ Res 23: 170–180

    Article  PubMed  CAS  Google Scholar 

  • Johansson A, Cammer P, Robertson B (1981) Effects of long-term nickel dust exposure on rabbit alveolar epithelium. Environ Res 25: 391–403

    Article  PubMed  CAS  Google Scholar 

  • Khan MF, Gupta GSD (1991) Cellular and biochemical indices of bronchoalveolar lavage for detection of lung injury following insult by airborne toxicants. Toxicol Lett 58: 239–255

    Article  PubMed  CAS  Google Scholar 

  • Kollmeier H, Witting C, Seemann J, Wittig P, Rothe R (1985) Increased chromium and nickel content in lung tissue. J Cancer Res Clin Oncol 110: 173–176

    Article  PubMed  CAS  Google Scholar 

  • Lockard VG, Kennedy RE (1976) Alteration in rabbit alveolar macrophages as a result of tramatic shock. Lab Invest 35: 501–506

    PubMed  CAS  Google Scholar 

  • Lundborg M, Cammer P (1984) Lysozyme levels in rabbit lung after inhalation of nickel, cadmium, cobalt, and copper chlorides. Environ Res 34: 335–342

    Article  PubMed  CAS  Google Scholar 

  • Menzel DB (1988) Planning and using PB-PK models: an integrated inhalation and distribution model for nickel. Toxicol Lett 43: 67–83

    Article  PubMed  CAS  Google Scholar 

  • Menzel DB, Deal DL, Tayyeb MI, Wolpert RL, Boger JR, Shoaf CR, Sandy J, Wilkinson K, Francovitch RJ (1987) Pharmacokinetic modeling of the lung burden from repeated inhalation of nickel aerosols. Toxicol Lett 38: 33–43

    Article  PubMed  CAS  Google Scholar 

  • Misra M, Rodriguez RE, Kasprzak KS (1990) Nickel induced lipid peroxidation in the rat: correlation with nickel effect on antioxidant defense system. Toxicology 64: 1–17

    Article  PubMed  CAS  Google Scholar 

  • Nriagu JO, Pacyna JM (1988) Quantitative assessment of worldwide contamination of air, water and soil by trace metals. Nature 333: 134–139

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JN, Holmes A, Evans JC, Evans N, Evans RJ, Morgan A (1985) The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation. Environ Res 36: 268–297

    Article  PubMed  CAS  Google Scholar 

  • Raabe OG, Yeh H-C, Newton GJ, Phalen RF, Velasquez DJ (1977) Deposition of inhaled monodisperse aerosols in small rodents, In: Walton WH (ed) Inhaled particles IV (part. 1). Pergamon Press, Oxford, pp 3–21

    Google Scholar 

  • Raithel HJ, Ebner G, Schaller KH, Schellmann B, Valentin H (1987) Problems in establishing norm values for nickel and chromium concentrations in human pulmonary tissue. Am J Ind Med 12: 55–70

    Article  PubMed  CAS  Google Scholar 

  • Slater TF (1984) Overview of methods used for detecting lipid peroxidation, In: Packer L (ed), Oxygen radicals in biological systems. Methods in Enzymology, vol 105. Academic Press, Orlando, pp 283–293

    Chapter  Google Scholar 

  • Smolelis AN, Hartsell SE (1949) The determination of lysozyme. J Bacteriol 58: 731–736

    PubMed  CAS  Google Scholar 

  • Sunderman FW Jr (1977) A review of the metabolism and toxicology of nickel. Ann Clin Lab Sci 7: 377–398

    PubMed  CAS  Google Scholar 

  • Suzuki KT, Kobayashi E, Ito Y, Ozawa H, Suzuki E (1992) Localization and health effects of lanthanum chloride instilled intratracheally into rats. Toxicology 76: 141–152

    Article  PubMed  CAS  Google Scholar 

  • Toshima N, Akino T (1972) Alveolar and tissue phospholipids of rat lung. Tohoku J Exp Med 108: 253–263

    Article  PubMed  CAS  Google Scholar 

  • Wroblewski F, LaDue JS (1995) Lactic dehydrogenase activity in blood. Proc Soc Exp Biol Med 90: 210–213

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirano, S., Shimada, T., Osugi, J. et al. Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats. Arch Toxicol 68, 548–554 (1994). https://doi.org/10.1007/s002040050112

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002040050112

Key words

Navigation