Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse.
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.
Sagai
M
M
National Institute for Environmental Studies, Research Team for Health Effects of Air Pollutions, Ibaraki, Japan.
Saito
H
H
Ichinose
T
T
Kodama
M
M
Mori
Y
Y
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005648:Fuel Oils / Q000633:toxicity*; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D005648:Fuel Oils; D006878:Hydroxides; D017382:Reactive Oxygen Species; D013481:Superoxides; D002084:Butylated Hydroxytoluene; D017665:Hydroxyl Radical; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase