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Abstract
To investigate the development of cross-tolerance to ozone (O3) rats were preexposed to a submicrometer cadmium chloride (CdCl2) aerosol (1.4 m/m3; 1 h). After 3 or 4 days of recovery the animals were challenged with O3 (3 mg/m3; 4 h). Lung tissue was analyzed before the challenge for protein content and lactate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase activities. Immediately before and 1 day after the O3 challenge, bronchoalveolar lavage fluid (BALF) was analyzed for protein and albumin. Histological examination and morphometry were performed before and after the challenge. The results were compared with an O3-preexposed group (3 mg/m3; 4 h; 3 days of recovery) and with a non-preexposed group.
Rats recovered 3 or 4 days from the CdCI, preexposure exhibited increased levels of antioxidant enzyme activities and protein content compared to the nonexposed group. The O3 preexposure did not affect these parameters.
The O3 challenge in the O3, preexposed group induced an increase of protein and albumin levels in BALF (41% and 79%, respectively). The increase was small compared to the increase in the naive group (500% and 950%, respectively). In the CdCl2 preexposed group with 3 days of recovery protein and albumin levels 1 day after the O3 challenge were decreased compared to the levels immediately before the challenge (-79% and -7%, respectively). In the CdCl2 preexposed group with 4 days of recovery the levels remained unchanged compared to the levels immediately before the O3 challenge.
Exposure to O3 following 3 days of recovery after preexposure to CdCl2 or O3 resulted in lower levels of protein and albumin in BALF compared to the non-preexposed lungs (58% and 29%, respectively, for protein; 48% and 24%, respectively, for albumin). Exposure to O3 after preexposure to CdCl2 and 4 days of recovery resulted in levels of 47% for protein and 40% for albumin cornpared to the control group after the challenge.
Morphometry of lung parameters indicated that in all preexposed groups, 1 day after the challenge, the extent of the inflammatory reaction was the same as before the challenge.
These biochemical and histopathological data indicate that the lungs suffered less damage when the O3 challenge was preceded by an exposure to either CdCl2 or O3 The results suggest that the development of (cross-) tolerance to pneumotoxic compounds is related to a nonspecific reaction of the lung to deep lung irritants. Damage to type I cells subsequently followed by proliferation of less vulnerable type II cells may play a major role in the development of tolerance.