Deloris J. Judy

LUNG RESPONSES TO HYPOTHYROIDISM, HYPERTHYROIDISM, AND LIPOPOLYSACCHARIDE CHALLENGE IN RATS

The objectives of this investigation were to study the effects of hypo- and hyperthyroidism on some factors involved in lung injury under basal conditions (air exposure) and during an inflammatory response induced by inhalation exposure to lipopolysaccharide (LPS; 100 µg/ml; 3 h) in adult rats. Thyroid status was altered by thyroidectomy or thyroxine injections for 15 d. Hyperthyroidism alone caused a greater degree of lung cell damage, an increase in the permeability of the alveolar-capillary barrier, a rise in the total number of phagocytic cells obtained by bronchoalveolar lavage (BAL), and enhanced nitric oxide (NO) release by phagocytic cells relative to that in euthyroid control animals. Hypothyroidism alone was associated with opposite effects. Exposure of animals to LPS produced inflammatory responses, which included significant increases in lung cell damage, permeability of the alveolar-capillary barrier, number of phagocytic cells obtained by BAL, and NO production by the phagocytic cells. In general, hyperthyroidism enhanced the effects of LPS, while hypothyroidism reduced LPS-induced responses. These results suggest that thyroid status alone can affect some of the factors involved in lung injury and also modulate some of the inflammatory effects of LPS. Hyperthyroidism tends to enhance lung injury, while hypothyroidism seems to reduce lung injury.

Relative effects of asbestos and wollastonite on alveolar macrophages

Rabbit alveolar macrophages were exposed in culture to chrysotile asbestos, wollastonite, or latex, and the effects on various biochemical and physiological parameters related to cellular viability and fibrogenicity were determined. Exposure of alveolar macrophages to asbestos, wollastonite, or latex for 3 d has no effect on oxygen consumption or cellular volume. However, treatment of alveolar macrophages with as little as 25 micrograms asbestos/ml for 1 d increases lysosomal enzyme release and decreases membrane integrity, i.e., decreases trypan blue exclusion and increases leakage of cytosolic enzymes. In contrast, exposure of alveolar macrophages to wollastonite or latex at 250 micrograms/ml does not induce lysosomal enzyme release or alter membrane integrity even after 3 d of exposure in culture. These data suggest that chrysotile asbestos damages rabbit alveolar macrophages, while wollastonite, a potential substitute for asbestos, is far less cytotoxic.

INHALATION OF COTTON DUST IS ASSOCIATED WITH INCREASES IN NITRIC OXIDE PRODUCTION BY RAT BRONCHOALVEOLAR LAVAGE CELLS

The inhalation of cotton or other organic dusts can cause alterations in pulmonary function, and these pulmonary effects appear, in part, due to endotoxin contamination of the dusts. Since endotoxin is a potent stimulus for the induction of nitric oxide (NO) synthesis, we examined whether the inhalation of cotton dust might also be associated with increases in NO production. Rats were exposed to normal air, cotton dust aerosol (40.6 3.7 mg/m3), or a nebulized aerosol of endotoxin (2.2 x 104 EU/m3) for 3 h, and responses were studied 18 h postexposure. Increases in inducible NO synthase (iNOS) production by bronchoalveolar lavage cells (BALC) from rats occurred following exposure to cotton dust or endotoxin as evidenced by increases in iNOS mRNA levels and in vitro nitrate and nitrite production. However, a contribution of NO to oxidant species generation by BALC, as indexed by luminol-dependent chemiluminescence, was observed only in endotoxin-exposed rats. These results indicated that while the inhalatio...

In vitro effects of straight-chain alkanes (n-hexane through n-dodecane) on rat liver and lung cytochrome P-450

To evaluate the effect of straight-chain alkanes on normal detoxication reactions, we studied the in vitro effect of the homologous series n-hexane through n-dodecane on two cytochrome P-450 (EC 1.14.14.1) enzyme activities. Benzo[a]pyrene hydroxylase (BaPOHase) and 7-ethoxycoumarin deethylase activities were measured in liver and lung microsomes of control and beta-naphthoflavone-treated rats. In the presence of 2 mM n-hexane through n-dodecane, liver BaPOHase activity decreased from 67% of control with n-dodecane to 21% of control with octane. Lung benzo[a]pyrene hydroxylase was insensitive to all tested alkanes at 2 mM. In the presence of 2 mM alkanes, liver 7-ethoxycoumarin deethylase activity decreased from 73% of control with n-octane to 28% with n-octane. Lung 7-ethoxycoumarin deethylase was also sensitive to the alkane series. In the presence of 2 mM alkane the greatest effect was obtained with n-octane and represented a 56% loss in activity. Alkane concentration-dependence measurements showed 0.02-0.20 mM as the sensitive region of the curve for n-octane with maximal loss of activity achieved at 0.20 mM. Liver ethoxycoumarin deethylase activity from beta-naphthoflavone-treated rats was less sensitive towards the reactive alkane, n-octane, than the activity from control rats. Double-reciprocal-plot analysis revealed the maximal velocity (Vmax) was decreased in the presence of 0.2 mM n-octane. Hence this hydrocarbon did not exert its effect solely as an alternate substrate. The data show the n-alkanes, n-hexane through n-dodecane, interfered with a normal detoxication pathway in a manner that was chainlength-dependent, tissue-specific, and dependent on the preexposure history of the animal.