Tuberc Respir Dis.  1995 Apr;42(2):184-205.

The Effect of Vitamin E on Bleomycin-InducedPulmonary Injury and Fibrosis in Rat: Comparison of Penicillamine- or Deferoxamine-Treated Group

• Jung SH
• Yong SJ
• Ahn CM
• Shin KC
• Choi IJ
• Cho S

Abstract

BACKGROUND
Pulmonary toxicity by bleomycin has multiple mechanisms including direct tissue toxicity due to oxygen-derived free radicals and indirect toxicity through amplification of pulmonary inflammation. To evaluate the effect of chelators or free radical scavenger to lung damage induced by bleomycin, penicillamine as a copper chelator, deferoxamine as an iron chelator and vitamin E as a free radical scavenger were administered.
METHODS
Two hundred Wistar rats were divided into five groups: Control, bleomycin treated, bleomycin-penicillamine treated, bleomycin-deferoxamine treated, and bleomycin-vitamin E treated groups. Rats sacrificed on day 1, day 3, day 4, day 7, day 14, and day 28 after treatment. Bronchoalveolar lavage, light microscopic and immunohistologic studies for type I, III, IV collagens, fibronectin, laminin and NBD phallicidin were evaluated.
RESULTS
There was a significant increase in the total cell counts of bronchoalveolar lavage on day 1 from all treated animals and vitamin treated group showed an abrupt decrease in total cell counts with decrease of neutrophils on day 3. Bleomycin-vitamin E treated group had the least histologic changes such as pulmonary fibrosis. The alveolar basement membranes were positive for type IV collegen and laminin. Basement membranes of bleomycin, bleomycin-penicillamine, or bleomycin-deferoxamine treated groups were disrupted and fragmented on day 4 or 7. The bleomycin-vitamin E treated group had intact basement membranes until day 28.
CONCLUSION
Bleomycin-induced pulmonary fibrosis was related to the severity of acute injury to oxygen radicals or activation of neutrophils and disruption of basement membrane. Vitamin E seemed to be the most effective antioxidant in the inhibition of bleomycin-induced pulmonary injury and fibrosis.

Keyword

Bleomycin; Pulmonary injury; Vitamin E; Oxygen radicals; Extracellular matrix

MeSH Terms

Animals
Basement Membrane
Bleomycin
Bronchoalveolar Lavage
Cell Count
Chelating Agents
Collagen
Copper
Deferoxamine
Extracellular Matrix
Fibronectins
Fibrosis*
Free Radicals
Iron
Laminin
Lung
Lung Injury
Neutrophils
Penicillamine
Pneumonia
Pulmonary Fibrosis
Rats*
Rats, Wistar
Reactive Oxygen Species
Vitamin E*
Vitamins*
Bleomycin
Chelating Agents
Collagen
Copper
Deferoxamine
Fibronectins
Free Radicals
Iron
Laminin
Penicillamine
Reactive Oxygen Species
Vitamin E
Vitamins