Acute lung injury from intratracheal exposure to fugitive residual oil fly ash and its constituent metals in normo- and spontaneously hypertensive rats.
We have recently shown that the spontaneously hypertensive (SH) rats with underlying cardiovascular disease exhibited greater pulmonary vascular leakage and oxidative stress than healthy normotensive (Wistar Kyoto, WKY) rats after a 3-day inhalation exposure to residual oil fly ash (ROFA) particles (Kodavanti et al., 2000). Since host responsiveness to a 3-day episodic ROFA inhalation could be different from a single acute exposure, we examined ROFA and its constituent metal (vanadium, V; nickel, Ni)-induced lung injury after a single intratracheal (IT) exposure. Male SH and WKY rats (12-13 wk) were IT instilled with either saline or ROFA (0.0, 0.83 or 3.33 mg/kg). The bronchoalveolar lavage fluid (BALF) was analyzed for lung injury markers at 24 and 96 h post-IT. Rats were also IT instilled with 0.0 or 1.5 micromol/kg of either VSO(4) or NiSO(4).6H(2)O in saline (equivalent to a dose of 2-3 mg ROFA), and assessed at 6 and 24 h post-IT. Basal levels of BALF protein, macrophages, and neutrophils, but not lactate dehydrogenase (LDH), were higher in control SH compared to control WKY rats. Lung histology of control SH rats exhibited mild focal alveolitis and perivascular inflammation; these changes were minimal in control WKY rats. ROFA-induced increases in BALF protein, and to a lesser extent in LDH, were greater in SH compared to WKY rats. ROFA IT was associated with the increases in BALF total cells in both strains (SH > WKY). BALF neutrophils increased at 24 h and macrophages at 96 h in a dose-dependent manner (SH > WKY). The increase in BALF neutrophils was largely reversed by 96 h in both rat strains. The V-induced increases in BALF protein and LDH peaked at 6 h post-IT and returned to control by 24 h in WKY rats. In SH rats, BALF protein and LDH were not affected by V. Ni caused BALF protein to increase in both strains at 6 and 24 h; however, the control values at 24 h were high in SH rats, and were not distinguishable from exposed rats. The Ni-induced increase in LDH activity was progressive over a 24-h time period (WKY > SH). The number of macrophages decreased following V and Ni exposure at 6 h, and this decrease was reversed by 24 h in both strains. V caused BALF neutrophils to increase only in WKY rats. The Ni-induced increase in BALF neutrophils was more dramatic and progressive than that of V, but was similar in both strains. Lung histology similarly revealed more severe and persistent edema, perivascular and peribronchiolar inflammation, and hemorrhage in Ni- than in V-exposed rats. This effect of Ni appeared slightly more severe in SH than in WKY rats. In summary, the acute single IT exposure to ROFA resulted in greater pulmonary protein leakage and inflammation in SH rats than in WKY rats. The metallic constituents of ROFA produced these effects in a strain-specific manner such that, at the dose level used, V caused pulmonary injury only in WKY rats, whereas Ni was toxic to both strains.
Kodavanti
U P
UP
Pulmonary Toxicology Branch, MD 82, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. kodavanti.urmila@epa.gov
Schladweiler
M C
MC
Richards
J R
JR
Costa
D L
DL
D000208:Acute Disease; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity*; D002452:Cell Count; D060729:Coal Ash; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000473:pathology; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009532:Nickel / Q000633:toxicity*; D052638:Particulate Matter; D011506:Proteins / Q000032:analysis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014639:Vanadium / Q000633:toxicity*
D000393:Air Pollutants; D060729:Coal Ash; D052638:Particulate Matter; D011506:Proteins; D014639:Vanadium; D002244:Carbon; D009532:Nickel; D007770:L-Lactate Dehydrogenase