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 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 stabilization 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 gamma-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.
Karam
H
H
Laboratoire de Physiopathologie Respiratoire, CHU St-Antoine, Paris, France.
Hurbain-Kosmath
I
I
Housset
B
B
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001761:Bleomycin / Q000633:toxicity*; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000975:Antioxidants; D001761:Bleomycin; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione