Effects of acetaminophen on the ultrastructure of isolated rat hepatocytes.
The effects of acetaminophen (AA) on the ultrastructure of isolated hepatocytes (IHC) of rat following incubation of IHC suspensions with AA were examined by electron microscopy. The effect of N-acetyl-p-benzoquinone imine (NAPQI), a putative toxic metabolite of AA, were also observed. IHC were prepared from livers obtained from phenobarbital-treated rats by collagenase perfusion method. With 5 and 20 mM AA, surface blebs mainly containing smooth endoplasmic reticulum (ER) occurred in IHC. Dilatation of Golgi apparatus, partial degranulation of rough ER and enlargement of mitochondria were also observed. The altered mitochondria showed a low electron-dense matrix with loss of mitochondrial granules. With 500 microM NAPQI, surface blebs containing various organelles occurred in IHC. Disorderly distributions of cytoplasmic organelles, mild dilatation of rough and smooth ER and cytoplasmic myeloid bodies were observed. The characteristic myeloid bodies were seemingly derived from degranulated rough ER.
Fujimura
H
H
Division of Biological Chemistry, National Institute of Hygienic Sciences, Tokyo, Japan.
Kawasaki
N
N
Tanimoto
T
T
Sasaki
H
H
Suzuki
T
T
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D016227:Benzoquinones / Q000633:toxicity; D002478:Cells, Cultured; D007097:Imines / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016227:Benzoquinones; D007097:Imines; D000082:Acetaminophen; C028473:N-acetyl-4-benzoquinoneimine