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The time course of responses to intratracheally instilled toxic Stachybotrys chartarum spores in rats

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Abstract

Stachybotrys chartarum is a fungal species that can produce mycotoxins, specifically trichothecenes. Exposures in the indoor environment have reportedly induced neurogenic symptoms in adults and hemosiderosis in infants. However, little evidence has linked measured exposures to any fungal agent with any health outcome. We present here a study that focuses on quantitatively assessing the health risks from fungal toxin exposure. Male, 10 week old Charles River-Dawley rats were intratracheally instilled with approximately 9.6 million Stachybotrys chartarum spores in a saline suspension. The lungs were lavaged 0 h (i.e., immediately post-instillation), 6, 24 or 72 h after instillation. Biochemical indicators (albumin, myeloperoxidase, lactic dehydrogenase, hemoglobin) and leukocyte differentials in the bronchoalveolar lavage fluid and weight change were measured. We have demonstrated that a single, acute pulmonary exposure to a large quantity of Stachybotrys chartarum spores by intratracheal instillation causes severe injury detectable by bronchoalveolar lavage. The primary effect appears to be cytotoxicity and inflammation with hemorrhage. There is a measurable effect as early as 6 h after instillation, which may be attributable to mycotoxins in the fungal spores. The time course of responses supports early release of some toxins, with the most severe effects occurring between 6 and 24 h following exposure. By 72 h, recovery has begun, although macrophage concentrations remained elevated.

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References

  1. Burge HA. Airborne allergenic fungi. Immunol Allergy Clinics N Am 1989; 9: 307-319.

    Google Scholar 

  2. Larsen FO, Christensen LH, Clementsen P, Gravesen S, Stahl Skov P, Norn S. Microfungi in indoor air are able to trigger histamine release by non-IgE-mediated mechanisms. Inflamm Res 1996; 45: S23-24.

    PubMed  Google Scholar 

  3. Rylander R, Persson K, Goto H, Yuasa K, Tanaka S. Airborne, β-1,3 glucan may be related to symptoms in sick buildings. Indoor Environ 1992; 1: 263-267.

    Google Scholar 

  4. Flannigan B. Mycotoxins in the air. Int Biodeterior 1987; 23: 73-78.

    Article  Google Scholar 

  5. Hendry KM, Cole EC. A review of mycotoxins in indoor air. J. Toxicol Environ Health 1993; 38: 183-198.

    PubMed  Google Scholar 

  6. Sorenson W. Mycotoxins as potential occupational hazards. Dev Ind Microbiol 1990; 31: 205-211.

    Google Scholar 

  7. Cooley J, Wong W, Jumper C, Straus D. Correlation between the prevalence of certain fungi and sick building syndrome. Occup Environ Med 1998; 55: 579-584.

    PubMed  Google Scholar 

  8. Croft WA, Jarvis BB, Yatawara CS. Airborne outbreak of trichothecene toxicosis. Atmos Environ 1986; 20: 549-552.

    Article  Google Scholar 

  9. Hintikka E-L. Human stachybotryotoxicosis. In: Wyllie T, Morehouse L, eds. Mycotoxic fungi, mycotoxins and mycotoxicosis, Vol. 3: Marcel Dekker, 1978: 87-89.

  10. Sudakin D. Toxigenic fungi in a water-damaged building: An intervention study. Am J Ind Med 1998; 34:183-190.

    Article  PubMed  Google Scholar 

  11. Bata A, Harrach B, Vanyi A, Lepom P. Macrocyclic trichothecene toxins produced by Stachybotrys atra. Acta Vet Hung 1988; 36: 221-227.

    PubMed  Google Scholar 

  12. Jarvis BB, Lee YW, Comezoglu SN, Yatawara CS. Trichothecenes produced by Stachybotrys atra from Eastern Europe. Appl Environ Microbiol 1986; 51: 915-918.

    PubMed  Google Scholar 

  13. Pasanen A, Nikulin J, Tuimainen M, Berg S, Parikka P, Hintikka E-L. Laboratory experiments on membrane filter sampling of airborne mycotoxins produce by Stachybotrys atra Corda. Atmos Environ 1993; 27A: 9-13.

    Google Scholar 

  14. Sorenson WG, Frazer DG, Jarvis BB, Simpson J, and Robinson VA. Trichothecene mycotoxins in aerosolized conidia of Stachybotrys atra. Appl Environ Microbiol 1987; 53: 1370-1375.

    PubMed  Google Scholar 

  15. Ueno Y. Mode of action of trichothecenes. Ann Nutr Aliment 1977; 31: 885-900.

    PubMed  Google Scholar 

  16. Bergmann F, Yagen B, Jarvis BB. The toxicity of macrocyclic trichothecenes administered directly into the rat brain. Toxicon 1992; 30: 1291-1294.

    Article  PubMed  Google Scholar 

  17. Bubien J, Woods Jr. W. Direct and reflex cardiovascular effects of trichothecene mycotoxins. Toxicon 1987; 25: 325-331.

    Article  PubMed  Google Scholar 

  18. Glavits R. Effect of trichothecene mycotoxins (satratoxin H and T-2 toxin) on the lymphoid organs of mice. Acta Vet Hung 1988; 36: 37-41.

    PubMed  Google Scholar 

  19. Hughes BJ, Hsieh GC, Jarvis BB, Sharma RP. Effects of macrocyclic trichothecene mycotoxins on the murine immune system. Arch Environ Contam Toxicol 1989; 18: 388-395.

    Article  PubMed  Google Scholar 

  20. Ohff V, Kwella M, Booth W. Untersuchungen zur toxizitat von Stachybotrys atra im hauttest an ratten. MH Vet Med 1985; 40: 774-776.

    Google Scholar 

  21. Schiefer H, Hancock D, Bhatti A. Systemic effects of topically applied trichothecenes. I. Comparative study of various trichothecenes in mice. J Vet Med A 1986; 33: 373-383.

    Google Scholar 

  22. Yoshizawa T, Ohtsubo K, Sasaki T, Nakamura K. Acute toxicities of satratoxins G and H in mice-a histopathological observation with special reference to the liver injury caused by satratoxin G. Proc Jap Assoc Mycotoxicol 1986; 23: 53-57.

    Google Scholar 

  23. Nikulin M, Reijula K, Jarvis BB, and Hintikka EL. Experimental lung mycotoxicosis in mice induced by Stachybotrys atra. Int J Exp Pathol 1996; 77: 213-218.

    Article  PubMed  Google Scholar 

  24. Nikulin M, Reijula K, Jarvis BB, Veijalainen P, Hintikka EL. Effects of intranasal exposure to spores of Stachybotrys atra in mice. Fundam Appl Toxicol 1997; 35: 182-188.

    Article  PubMed  Google Scholar 

  25. Le Bars J, Le Bars P. Toxinogenesis and development conditions of Stachybotrys atra in France. Acta Vet Scand Suppl 1991; 87: 349-351.

    Google Scholar 

  26. Le Bars J, Le Bars P. Etude du nuage de spores de Stachybotrys atra contaminant de pailles: risques dinhalation. Bull Soc Fr Mycol Med 1985; 14: 321-324.

    Google Scholar 

  27. Henderson RF. Commentary on Cellular and biochemical indices of bronchoalveolar lavage for detection of lung injury following insult by airborne toxicants by M. Firoze Khan and G.S.D. Gupta [comment]. Toxicol Lett 1991; 58: 235-238.

    Article  PubMed  Google Scholar 

  28. Khan MF, Gupta GS. Cellular and biochemical indices of bronchoalveolar lavage for detection of lung injury following insult by airborne toxicants [see comments]. Toxicol Lett 1991; 58: 239-255.

    Article  PubMed  Google Scholar 

  29. Blythe S, England D, Esser B, Junk P, Lemanske Jr. RF. IgE antibody mediated inflammation of rat lung: Histologic and bronchoalveolar lavage assessment. Am Rev Respir Dis 1986; 134: 1246-1251.

    PubMed  Google Scholar 

  30. Lecours R, Laviolette M, Cormier Y. Bronchoalveolar lavage in pulmonary mycotoxicosis (organic dust toxic syndrome). Thorax 1986; 41: 924-926.

    PubMed  Google Scholar 

  31. Pagano L, Pagliari G, Basso A, Marra R, Sica S, Frigieri L, Morace G, Ardito F, Leone G. The role of bronchoalveolar lavage in the microbiological diagnosis of pneumonia in patients with haematological malignancies. Ann Med 1997; 29: 535-540.

    PubMed  Google Scholar 

  32. Eppley RM. Sensitivity of brine shrimp (Artemia salina) to trichothecenes. J Assoc Off Anal Chem 1974; 57: 618-620.

    PubMed  Google Scholar 

  33. Beck BD, Brain JD, Bohannon DE. An in vivo hamster bioassay to assess the toxicity of particulates for the lungs. Toxicol Appl. Pharmacol 1982; 66: 9-29.

    Article  PubMed  Google Scholar 

  34. U.S. National Research Council. Biologic Markers in Pulmonary Toxicology. Washington, D.C.: National Academy Press, 1989.

    Google Scholar 

  35. Braun J, Mehnert A, Dalhoff K, Wiessmann KJ, Ratjen F. Different BALF protein composition in normal children and adults. Respiration 1997; 64: 350-357.

    PubMed  Google Scholar 

  36. Cheng PW, Boat TF, Shaikh S, Wang OL, Hu PC, Costa DL. Differential effects of ozone on lung epithelial lining fluid volume and protein content. Exp Lung Res 1995; 21: 351-365.

    PubMed  Google Scholar 

  37. Harrach B, Nummi M, Niku-Paavola ML, Mirocha CJ, Palyusik M. Identification of water-soluble toxins produced by a Stachybotrys atra strain from Finland. Appl Environ Microbiol 1982; 44: 494-495.

    PubMed  Google Scholar 

  38. Leong BKJ, Coombs JK, Sabaitis CP, Rop DA, Aaron CS. Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, in34 tratracheal instillation or nose-only inhalation in rats. J Appl Toxicol 1998; 18: 149-160.

    Article  PubMed  Google Scholar 

  39. Brain JD, Knudson DE, Sorokin SP, Davis MA. Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalation. Environ Res 1976; 11: 13-33.

    Article  PubMed  Google Scholar 

  40. Henderson RE, Driscoll KE, Harkema JR, Lindenschmidt RC, Chang I-Y, Maples KR, Barr EB. A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats. Fundam Appl Toxicol 1995; 24: 183-197.

    Article  PubMed  Google Scholar 

  41. Samsonov P, Samsonov A. The respiratory mycotoxicoses (pneumonomycotoxicoses) experimentally. In: Bilay V, ed. Mycotoxicosis of man and agricultural animals. Washington, D.C.: U.S. Joint Publications Research Service, 1960: 140-150.

    Google Scholar 

  42. Rao CY, Brain JD, Burge HA. Reduction of pulmonary toxicity of Stachybotrys chartarum spores by methanol extraction of mycotoxins. Appl Environ Microbiol 2000; 66: 2817-2821.

    Article  PubMed  Google Scholar 

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Rao, C.Y., Burge, H.A. & Brain, J.D. The time course of responses to intratracheally instilled toxic Stachybotrys chartarum spores in rats. Mycopathologia 149, 27–34 (2000). https://doi.org/10.1023/A:1007239017018

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