Hepatotoxicity of combined treatment with cisplatin and gentamicin in the guinea pig.
The damaging effects on the liver tissue of treatment with cisplatin followed by the aminoglycoside antibiotic gentamicin were studied in guinea pigs. The ultrastructural findings revealed foci of damage in the liver parenchyma, including its vascular component. Injurious effects to cytoplasmatic organelles such as mitochondria and endoplasmic reticulum as well as to nuclei were observed. In addition, abundance of lysosomes, autophagic vacuoles, and amorphous-granular bile in the lumina of bile canaliculi was found. Focal sinusoidal lining damage and capillarization of sinusoids were also present. In vascular lumina, some erythrocytes showed a deformed shape ("ropalocytosis"). Taken together, these findings indicate that the combined treatment with cisplatin followed by gentamicin is toxic to components of liver tissue. Since toxic changes have been shown in vessels of the inner ear and in renal-glomerular capillaries, the present observations of hepatotoxicity indicate the potential vascular damage to various tissues. The injurious effects of the cisplatin-aminoglycoside combination should be considered during its use in clinical conditions.
Kohn
Sarah
S
Electron Microscopy Unit, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. skohn@tx.technion.ac.il
Fradis
Milo
M
Robinson
Eliezer
E
Iancu
Theodore C
TC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001648:Bile Canaliculi / Q000187:drug effects / Q000648:ultrastructure; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D005839:Gentamicins / Q000633:toxicity*; D006168:Guinea Pigs; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D005839:Gentamicins; D002945:Cisplatin