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 or...

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Bibliographic Details
Published in:Ultrastructural pathology 2005-03, Vol.29 (2), p.129-137
Main Authors: Kohn, Sarah, Fradis, Milo, Robinson, Eliezer, Iancu, Theodore C.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - toxicity
Antineoplastic Agents - toxicity
Bile Canaliculi - drug effects
Bile Canaliculi - ultrastructure
cancer therapy
cisplatin
Cisplatin - toxicity
Dose-Response Relationship, Drug
Drug Therapy, Combination
Endothelium, Vascular - drug effects
Endothelium, Vascular - ultrastructure
gentamicin
Gentamicins - toxicity
Guinea Pigs
hepatotoxicity
Liver - blood supply
Liver - drug effects
Liver - pathology
Microscopy, Electron, Transmission
Organelles - drug effects
Organelles - ultrastructure
ultrastructure
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Summary: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.
ISSN:0191-3123
1521-0758
DOI:10.1080/019131290924018