Effects of Cigarette Smoke on the Glutathione Status of the Upper and Lower Respiratory Tract of Rats

Abstract

Endogenous antioxidants, like the tripeptide glutathione (CSH), protect the respiratory airways from potentially injurious agents within inhaled pollutants like cigarette smoke. The purpose of this study was to determine the effects of cigarette smoke exposure on respiratory tract tissue. Twenty-four F344/N male rats were exposed to cigarette smoke (249 mg total particulate matter/m³) or filtered air for 6 h/day for 9 days. Rats were sacrificed 1 day or 14 days after the last exposure. The most dramatic changes in CSH concentrations occurred in the tissues of the nasal cavity 1 day following exposure, with tissues from the proximal nasal airways showing the greatest response. These same proximal nasal airway tissues also had the greatest histopathological changes. Within 2 wk after exposure, the CSH concentrations in the nasal tissues from smoke-exposed rats were similar to air-exposed controls, and there was only minimal histopathological evidence of tissue alteration. CSH concentrations were not significantly elevated in the left extrapulmonary bronchi or main axial airway, nor were there any histologic alterations evident in these tissues at any time point. Thus, the extent of the cellular CSH response paralleled the extent of respiratory tract tissue injury and recovery. Our results suggest that the reactive agent(s) in cigarette smoke cause increased CSH in nasal tissue and that squamous metaplasia occurs in nasal surface epithelium. Both changes, however, are resolved by 14 days after a short-term cigarette smoke exposure.