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 (I T) instillation or by acute aerosol inhalation, and pulmonary clearanc e of Ni and pulmonary inflammatory responses were studied. The half-ti me of Ni in the lung (initial lung burden = 50 mu g Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention i n the lung tissue following IT instillation of NiSO4 was saturable wit h reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were e valuated by biochemical, elemental and cytological indicators in bronc hoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Act ivities of lactate dehydrogenase and beta-glucuronidase, contents of l ysozyme, protein, sulfur and calcium, and the number of polymorphonucl ear leukocytes were increased with a peak at 2-3 days post-instillatio n, while BALF alkaline phosphatase (ALP) activity was significantly de creased after IT instillation of NiSO4. Lung tissue ALP activity was a lso decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type Il cells (a major source of BALF ALP). Thiobarbituric acid reacting s ubstances in the lung tissue were not changed by NiSO4, suggesting tha t lipid peroxidation plays a minimal, if any role, in the Ni-induced i nflammation in the rat lung.