Effects of 2,2'-azobis (2-amidinopropane) hydrochloride in vivo and protection by vitamin E.
2,2'-Azobis (2-amidinopropane) hydrochloride (AAPH), a compound that decomposes spontaneously to generate free radicals, was administered intraperitoneally to rats. High doses (greater than or equal to 70 mg/kg) were always fatal within a few hours. At nonlethal levels, AAPH was found to be absorbed into the circulation where it remained with a half-life of about 30 min. Lipid peroxidation was observed to occur in the liver and, to a much smaller extent, the kidney and heart of treated rats; levels of thiobarbituric acid-reactive substances were unchanged in the lung and brain, and significantly reduced in the plasma. Serum lipid levels were also lower in the AAPH-treated rats. Orally administered vitamin E, but not its water soluble analog, prevented the accumulation of TBA-reactive substances in the livers of AAPH-treated rats in a dose-dependent manner, but had no effect on mortality or the changes in serum lipid levels. The data suggest that intraperitoneally administered AAPH is absorbed into the circulation and can induce lipid peroxidation in vivo, but that toxicity may also arise through nonradical mechanisms. Furthermore, the free radical toxicity of AAPH in vivo may not be so general as previously suggested.
Dooley
M M
MM
Eisai Research Laboratories, Eisai Co., Ltd., Tokyo, Japan.
Sano
N
N
Kawashima
H
H
Nakamura
T
T
D000578:Amidines / Q000097:blood / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009026:Mortality; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology*
D000578:Amidines; D000975:Antioxidants; D005609:Free Radicals; D008055:Lipids; D014810:Vitamin E; C046728:2,2'-azobis(2-amidinopropane)