Protection of Cigarette Smoke‐Induced Lung Fibrosis in Guinea Pigs by Inhalation of Aerosolic All‐Trans Retinoic Acid

Abstract

We reported earlier that both mainstream (MS) and secondhand (SH) cigarette smoke exposure to guinea pigs caused lung injury with accumulation of amorphous granular materials in alveolar space and an increase in the levels of retinol. We previously reported that the accumulation of retinol in lung was associated with a decrease in the levels of retinoic acid implying an abnormality in lung retinoid metabolism and signaling. The objective of the present study was to demonstrate whether the lung injury is due to fibrosis and whether inhalation of aerosolic all-trans retinoic acid (ATRA) immediately after smoke exposure can protect against smoke-induced lung fibrosis. Six weeks old male guinea pig were exposed twice daily for 6 weeks to MS or SH smoke from 3 1R3F cigarettes. The sham control group (SC) received a treatment identical to smoke-exposed groups but in the absence of cigarettes. Four animals from each group received daily either aerosolic ATRA (2.78mM) or vehicle twice for 20 min/day after smoke exposure. Morphological analysis of lungs showed deleterious alterations in the lungs of both MS and SH groups and accumulation of severe trichrome-positive (blue dye) materials in throughout the region of lung in comparison to the normal. ATRA treatment showed significant protection against lung damage; however the protection was more evident in MS than SH groups. The mechanism by which ATRA aerosol protects cigarette smoke-induced lung fibrosis is under investigation. (Supported by NIH grant: 1R03HL095419-01A1).