Hepatic accumulation and hepatotoxicity of luteoskyrin in mice.
HPLC analysis revealed that luteoskyrin administered orally to male mice accumulated selectively in the liver, with minor distribution to the serum and kidneys. Elevation of serum GOT and GPT values was maximal 3 days after administration. In mice administered this mycotoxin intravenously, selective accumulation was also observed in the liver, and the half-life of hepatic luteoskyrin in males was significantly longer than that in females. Increment of serum transaminases was also marked in males with maximum accumulation at 24 h after administration. Histopathologically, cellular membrane damage was an early effect of luteoskyrin on cell necrosis, and these morphological changes were also marked in males. Luteoskyrin also elevated hepatic lipid peroxides, the maximum elevation being 8 h after injection; this increase was suppressed by alpha-tocopherol and Bi(NO3)3. HPLC-ECD analysis indicated that the level of 8-hydroxy-deoxyguanosine, one of the markers of hydroxy-radical-mediated modification of DNA guanine residues, was increased in hepatic DNA. These findings indicate that luteoskyrin has a high affinity for the liver, resulting in induction of lipid peroxidation, hepatocellular membrane damage, and elevation of serum transaminase activities. It is suggested that the hydroxy radicals derived from this anthraquinone contribute to these toxicological changes.
Masuda
T
T
Biological Research Laboratories, Lederle Ltd., Shiki, Japan.
Ito
J
J
Akuzawa
S
S
Ishii
K
K
Takagi
H
H
Ueno
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D016166:Free Radical Scavengers; D006900:Hydroxylation; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000493:pharmacokinetics / Q000633:toxicity*; D009336:Necrosis; D013997:Time Factors
D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D009285:Naphthoquinones; C100224:luteoskyrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine