Nephrotoxicity of combined treatment with cisplatin and gentamicin in the guinea pig: glomerular injury findings.
The drugs cisplatin and gentamicin are given consecutively to various cancer patients suffering from infections. Little information exists about the ultrastructural alterations of kidney glomeruli caused by treatment with these drugs. Renal glomeruli of guinea pigs treated with cisplatin alone and in combination with gentamicin were studied by transmission electron microscopy. The findings revealed foci of damage induced by cisplatin and especially by cisplatin/gentamicin in all glomerular components: glomerular capillaries, including their endothelial cells; basement membrane, epithelial podocytes, mesangial cells, and parietal cells of Bowman's capsule. The damage was expressed by endothelial cytoplasmic extrusions into the vascular lumen, thickening and lamination of capillary basement membrane, focal foot process fusion of podocytes, vacuolization in cytoplasm of endothelial cells of epithelial podocytes and of parietal cells, and the presence of lipid bodies and myeloid bodies in all glomerular cell types. Additionally, injurious effects to cytoplasmic organelles such as mitochondria, nuclei, and endoplasmic reticulum were observed. The results indicate that cisplatin alone and in combination with gentamicin is toxic to renal glomerular tissue. Since these drugs were previously found toxic for strial capillaries in the inner ear and since the main glomerular component is the glomerular capillaries, potential vascular damage and vascular complications in different body systems have to be taken into consideration when these drugs are needed in clinical use.
Kohn
Sarah
S
Electron Microscopy Unit, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. skohn@tx.technion.ac.il
Fradis
Milo
M
Ben-David
Jacob
J
Zidan
Jamal
J
Robinson
Eliezer
E
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002196:Capillaries / Q000648:ultrastructure; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003593:Cytoplasm / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity; D006168:Guinea Pigs; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure*; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure
D005839:Gentamicins; D002945:Cisplatin