Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats.
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 micrograms 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 beta-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.
Hirano
S
S
Regional Environment Division, National Institute for Environmental studies, Ibaraki, Japan.
Shimada
T
T
Osugi
J
J
Kodama
N
N
Suzuki
K T
KT
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004602:Elements; D007249:Inflammation / Q000139:chemically induced*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009532:Nickel / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D004602:Elements; C029938:nickel sulfate; D009532:Nickel