Vitamin E reduces bleomycin-induced lung fibrosis in mice: biochemical and morphological studies.

Abstract

Bleomycin is a widely used antineoplastic drug which produces dose- and time-dependent interstitial pulmonary fibrosis in humans. The mechanism of bleomycin-induced lung injury is not well understood. However, current data show that bleomycin can generate reactive oxygen species such as superoxide and hydroxyl radicals. The antioxidant role of vitamin E in biological systems is well known. We investigated the effect of vitamin E on bleomycin-induced lung fibrosis in mice biochemically and histologically. Animals were divided into four groups: control, saline + vitamin E (S/Vit E), bleomycin + saline (Bleo/S) and bleomycin + vitamin E (Bleo/Vit E). Bleomycin was administered subcutaneously at a dose of 10 mg/kg in Bleo/S and Bleo/Vit E groups, and vitamin E was administered intraperitoneally at a dose of 15 mg/animal in S/Vit E and Bleo/Vit E groups twice weekly for 4 weeks. The control group received saline. As a marker of collagen amount or fibrosis in lung tissue, hydroxyproline and soluble protein content were measured and hydroxyproline/soluble protein ratio per gram wet lung tissue was calculated. For hydroxyproline and protein determinations, and histologic examination of lung tissue, 6 mice from the control and S/Vit E groups and 7 mice from the Bleo/S and Bleo/Vit E groups were killed at at 4, 6 and 8 weeks after administration of bleomycin. The mean hydroxyproline/soluble protein ratio of the Bleo/Vit E group was significantly lower than that of the Bleo/S group and significantly higher than those of the control and S/Vit E groups at 6 and 8 weeks (p < 0.05). Parallel with the biochemical findings, the grade of the histological lesions in the Bleo/Vit E group was lower than that in the Bleo/S group, but higher than those of the S/Vit E and control groups (p < 0.05). These results suggest that a high dose of vitamin E considerably reduces the fibrotic effect of bleomycin on lung tissue in mice.