Role of lipid-derived free radical in bleomycin-induced lung injury in mice: availability for ESR spin trap method with organic phase extraction.
Bleomycin is well known as causative molecule for acute lung injury and interstitial pneumonia. The free radical production from bleomycin is thought to play an important role in the pathogenesis of acute lung injury and interstitial pneumonia. However, there was no direct evidence of free radical production in this model. Therefore, we examined in vivo radical production by mice treated with a bleomycin using electron spin resonance with the spin trap, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. Six hours after instillation of bleomycin, the lung exposed to bleomycin gave a lipid-derived free radical adduct, which would support evidence for in vitro lipid peroxidation resulting from bleomycin administration. In the treatment of deferoxamine, chelating agent for iron and other metals, to reduce the bleomycin induced free radical production, parallel to decrease the lipid-derived free radical production by deferoxamine, pathophysiological findings of lung injuries were improved by deferoxamine. In conclusion, this is a first paper of in vivo direct evidence of production of free radical from bleomycin-induced lung injury. It is suggested that this method may be used in many kinds of lung disease models, which have potentials of free radical production to cause lung damage.
Sato
Keizo
K
Divisions of Pharmacology and Therapeutics, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Kumamoto 862-0973, Japan. keizokun@gpo.kumamoto-u.ac.jp
Tashiro
Yasumasa
Y
Chibana
Satsuki
S
Yamashita
Akihisa
A
Karakawa
Tomohiro
T
Kohrogi
Hirotsugu
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000931:Antidotes / Q000494:pharmacology; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003676:Deferoxamine / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008171:Lung Diseases / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000737:chemistry; D013113:Spin Labels; D019097:Spin Trapping
D000900:Anti-Bacterial Agents; D000931:Antidotes; D005609:Free Radicals; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; D001761:Bleomycin; D003676:Deferoxamine