Sensitivity of lungs of aging Fischer 344 rats to ozone: assessment by bronchoalveolar lavage

Abstract

Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability of protein changes was higher in senescent (24-mo-old) rats. By comparison to juvenile (2-mo-old) and adult (9-mo-old) rats, senescent animals had higher increases of interleukin-6 (up to 10-fold higher) and N-acetyl-beta-D-glucosaminidase (NAGA; 2-fold higher) in lung lavage after ozone. Ascorbic acid was lower in lungs of senescent rats (one-half of juvenile values), and acute ozone exposure brought a further decrease in lung ascorbate. Whereas alveolar protein transudation was attenuated after ozone exposure on 4 days, persistent elevation of NAGA in senescent rats suggested only partial adaptation. Injection of endotoxin did not modify the patterns of effects. Incorporation of 18O-ozone into macrophages and surfactant was not different between age groups, indicating that the magnified biological responses in senescent rats were not dominated by differences in internal dose of ozone. The results indicate that senescent rats respond differently than juvenile and adult rats to lung injury.

Role of interleukin-6 in murine airway responses to ozone

“…Together, these results suggest that IL-6 has the capacity to modulate airway responsiveness. Because IL-6 has been shown by many investigators, including ourselves, to be induced by O 3 (3,8,17,31,33,34,41), we reasoned that IL-6 might be acting to attenuate O 3 -induced AHR. Our results indicate that this is not the case, since baseline airway responsiveness and O 3 -induced AHR were not different in IL-6 ϩ/ϩ and IL-6 Ϫ/Ϫ mice, even though IL-6 mRNA was detectable following both room air and O 3 exposure.…”

“…The inflammatory response includes the generation of numerous cytokines and chemokines, as well as an influx of polymorphonuclear leukocytes (3,8,17,20,22,25,31,33,41,48). O 3 also causes airway hyperresponsiveness (AHR) (10,22,27,28,33,35,47).…”

“…In many species, IL-6 is released into bronchoalveolar lavage fluid (BALF) upon acute exposure to O 3 (31,33,41). There is also increased IL-6 mRNA in the lungs of mice exposed to O 3 (17).…”

Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults

“…The lung is continuously exposed to oxidative stress while reduced levels of antioxidant molecules such as ascorbic acid and glutathione (Canada et al, 1995;Vincent et al, 1996) and decreased activity of antioxidant enzymes such SOD and glutathione peroxidase are produced as it ages. In addition, induction of HO-1, which is involved in cellular protection against oxidative stress, is defective in lung of aged mice (Ito et al, 2009).…”

Environmental Determinants of Lung Aging

“…109 Overall, the cellular and biochemical effects of ozone exposure appear greater in senescent Fisher 344 rats (24 months old) compared to juvenile or adult rats. 29,110 In humans, pulmonary toxicity to ozone appears to be dependent on the effective dose which, in turn, depends upon ventilatory rates. 111,112 Thus, in acute exposure studies, younger individuals appear to show greater adverse effects than older individuals.…”