Effects of vitamin A treatment on hyaluronan and water accumulation during the early inflammatory phase of bleomycin-induced lung injury in rats

Abstract

The purpose of this study was to investigate the effect of vitamin A treatment on bleomycin-induced lung injury, especially during the early phase of alveolitis. The rats in the two treatment groups were given bleomycin intratracheally and oil vehicle (BO) or vitamin A (BA) orally. The rats in the control groups were given saline intratracheally and oil vehicle (CO) or vitamin A (CA) orally. Rats were killed 4, 7, and 30 days after bleomycin administration. Histologic signs of inflammation and fibrotic injury showed larger decreases in the BA group compared with the BO group at 7 days. After 30 days, most signs of inflammation had disappeared, and focal areas with further increased septal fibrosis were seen in the BO group and to a lesser extent in the BA group. The relative water content (%H 2O) in the lung tissue was significantly increased at 4 and 7 days in the BA and BO groups compared with the CA and CO groups, but not at 30 days. No significant differences in %H 2O values were found between the BA and BO groups at any time. Hyaluronan levels at 4 and 7 days in the BO group were significantly higher than in the CO group at 7 days. No other differences between groups were seen in hyaluronan levels. The messenger ribonucleic acid level for pro-alpha1(I) collagen in the BA group was reduced compared with the BO group but was higher than in the controls (groups CO and CA) after 7 days (n = 2 in each group). In bronchoalveolar lavage, performed in separate groups on day 4 after bleomycin administration, significant increases in hyaluronan levels and in the number of inflammatory cells were seen between both the BA and BO groups and the CO group, but no differences were observed between the BA and BO groups. These results indicate that vitamin A treatment does not inhibit early alveolitis in bleomycin-induced lung injury, although retinoids may partly modulate the later fibrotic phase in this experimental model.