The problem of whether or not
active oxygen species are involved in
pulmonary injury by
diesel exhaust particles (
DEP) was investigated. We found that
DEP could produce
superoxide O2.- and
hydroxyl radical (.
OH) in vitro without any
biological activating systems. In this reaction system, O2.- and .
OH productions were inhibited by addition of
superoxide dismutase (SOD) and
dimethylsulfoxide, respectively.
DEP which were washed with
methanol could no longer produce O2.- and .
OH, indicating that active components were extractable with organic
solvents. These
oxygen radicals were also identified by electron spin resonance (ESR) measurement. Furthermore,
DEP instilled intratracheally to mouse caused high mortality at low dose, although
methanol-washed
DEP did not kill any mouse. The cause of death seemed to be
pulmonary edema mediated by endothelial cell damage. The instilled
DEP markedly decreased the activities of SOD,
glutathione peroxidase, and
glutathione S-transferase in mouse lungs. On the other hand, the death rate and
lung injury were markedly prevented by
polyethylene glycol conjugated SOD (
PEG-SOD) pretreatment prior to
DEP administration. The mortality and
lung injury by
DEP were also suppressed by
butylated hydroxytoluene (
BHT) pretreatment. From these results, it was suggested that most parts of
DEP toxicity in lungs are due to
active oxygen radicals such as O2.- and .
OH, and that the cause of death is due to
pulmonary edema mediated by endothelial cell damage.