Sex differences in bronchiolar epithelial injury and repair following naphthalene inhalation in albino rats: a possible role of inducible nitric oxide

ABSTRACT

Airway injury and repair are implicated in the pathogenesis of lung diseases. Sex affects the severity of lung diseases. Naphthalene [NA] is an environmental contaminant. Clara cells are capable of detoxifying several pulmonary toxicants. To determine whether there is a sex-based difference in the injury and regenerative response to NA inhalation, and the possible role of inducible nitric oxide synthase [iNOS]. Thirty-six adult male and female albino rats were used. Rats were exposed to air [group I; control] or NA vapor for 4 h, and then sacrificed after 6 h [group II], 12 h [group III], 24 h [group IV], 14 days [group V], and 21days [group VI]. The lungs were used for histological and immunohistochemical studies. Exfoliation scoring and statistical analysis were carried out. Inhalation of NA induced bronchiolar cell exfoliation that started at 6 h and peaked at 24 h after inhalation in both sexes. Male bronchiolar epithelium fully regenerated by 14 days, whereas females showed some exfoliated cells in the lumen that disappeared by 21 days. In both sexes, the mean exfoliation score [MES] was significantly higher in groups III and IV compared with their controls. MES was significantly higher in females compared with males in group III and V. The expression of iNOS increased with time after NA inhalation. After 14 days, there was an apparent decrease in iNOS expression in both sexes. It was more obvious in female rats than males during the same period. Injury occurred earlier, with more affected cells in female bronchioles, whereas regeneration occurred earlier in males. Increased iNOS expression indicated a role of NO production in bronchiolar damage. The difference in iNOS expression in both sexes could provide a new mechanism in explaining sex differences in bronchiolar cell injury and repair