| Abstract: | Bleomycin (BLM) induces lung inflammation and subsequent fibrosis in human and in animal models. Alveolar epithelial type 2 cells (T2 cells) are known to play a crucial role in the repair process after BLM injury. We hypothesized that resistance of T2 cells to BLM-damage was associated with an increase in their antioxidant system activity. We developed an animal model of lung lesions preceding fibrosis, using daily intraperitoneal administration of BLM (1.5 mg/day over 7 and 14 days). We observed a body weight stablization in BLM-treated rats from the third day. After 14 days of BLM treatment, the number of cells recovered by bronchoalveolar lavage was significantly increased (p<0.05), with a dramatic increase (p<0.01) in the percentage of neutrophils associated with a decrease in macrophage percentage (p<0.01). No evidence of fibrosis was seen by microscopic studies at this time. However, T2 cells in 14-day-treated rats were swollen with enlarged lamellar inclusion bodies. Biochemical study of freshly isolated T2 cells displayed a significant decrease of lactate dehydrogenase (LDH) released by these cells when isolated from 14-day-treated rats as compared with 7-day. By contrast, BLM induced an increase in superoxide dismutase (SOD) and glutathione peroxidase activities. Cell content of glutathione was decreased and  -glutamyl transpeptidase activity was markedly increased. These results show that BLM induces changes in the antioxidant system of T2 cells, particularly in the glutathione system. |
