ANTIOXIDANT ACTIVITY IN ALVEOLAR EPITHELIAL TYPE-2 CELLS OF RATS DURING THE DEVELOPMENT OF BLEOMYCIN INJURY

Bleomycin (BLM) induces lung inflammation and subsequent fibrosis in h uman and in animal models. Alveolar epithelial type 2 cells (T2 cells) are known to play a crucial role in the repair process after BLM inju ry. We hypothesized that resistance of T2 cells to BLM-damage was asso ciated with an increase in their antioxidant system activity. We devel oped an animal model of lung lesions preceding fibrosis, using daily i ntraperitoneal administration of BLM (1.5 mg/day over 7 and 14 days). We observed a body weight stablization in BLM-treated rats from the th ird day. After 14 days of BLM treatment, the number of cells recovered by bronchoalveolar lavage was significantly increased (p < 0.05), Wit h a dramatic increase (p < 0.01) in the percentage of neutrophils asso ciated with a decrease in macrophage percentage (p < 0.01). No evidenc e of fibrosis was seen by microscopic studies at this time. However, T 2 cells in 14-day-treated rats were swollen with enlarged lamellar inc lusion bodies. Biochemical study of freshly isolated T2 cells displaye d a significant decrease of lactate dehydrogenase (LDH) released by th ese cells when isolated from 14-day-treated rats as compared with 7-da y. By contrast, BLM induced an increase in superoxide dismutase (SOD) and glutathione peroxidase activities. Cell content of glutathione was decreased and gamma-glutamyl transpeptidase activity was markedly inc reased. These results show that BLM induces changes in the antioxidant system of T2 cells, particularly in the glutathione system.