The effects of alpha-phenyl-tert-butyl nitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice.
In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.
Yamashita
T
T
Department of Animal Disease Control, Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Ohshima
H
H
Asanuma
T
T
Inukai
N
N
Miyoshi
I
I
Kasai
N
N
Kon
Y
Y
Watanabe
T
T
Sato
F
F
Kuwabara
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003300:Copper; D003497:Cyclic N-Oxides; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D007565:Jaundice / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D051381:Rats; D011922:Rats, Mutant Strains; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015431:Weight Loss
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; C029217:phenyl-N-tert-butylnitrone; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine