Sarah Kohn

Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis

The toxic effects of cisplatin (cis‐diamminedichloroplatinum [II]) on the organ of Corti are well established. Few and conflicting data on this drugs effects on the stria vascularis exist. The present study presents animal experiments on the toxic effects of cisplatin in the stria vascularis and in the organ of Corti. Cisplatin‐induced toxicity in albino and pigmented guinea pigs was evaluated morphologically and functionally, using light and transmission electron microscopy as well as auditory brainstem‐evoked potentials on the organ of Corti and the stria vascularis. The results showed variability in hearing thresholds, ranging from no change to hearing loss of 30 dB, and prominent damage in the organ of Corti and in the stria vascularis. The toxic effects to both the organ of Corti and the stria vascularis should be considered when cisplatin is used in chemotherapy.

ENDOTHELIAL INJURY OF CAPILLARIES IN THE STRIA VASCULARIS OF GUINEA PIGS TREATED WITH CISPLATIN AND GENTAMICIN

The drugs cisplatin and gentamicin are used for treatment of various cancer patients suffering from infection. The authors report a detailed electron microscopic study of blood vessels in stria vascularis of guinea pigs after treatment with cisplatin alone and in combination with gentamicin. The most distinctive features expressing endothelial cellular injury were mitochondrial, including occasional paracrystalline inclusions; electron-lucent foci with depleted organelles; intracytoplasmic vacuole formations; lipid bodies; cytoplasmic extrusions located on the luminal surface; and severe luminal constriction of part of the vessels from animals treated with the combined drugs. The study suggests that the damage to strial capillaries due to treatment with cisplatin alone and in combination with gentamicin may contribute to the injurious effects of these drugs on the strial tissue. Furthermore, the results of this study may enlarge the awareness of the potential vascular damage and vascular complications in additional body systems after medical use of cisplatin alone or in combination with gentamicin.

Toxic effects of cisplatin alone and in combination with gentamicin in stria vascularis of guinea pigs.

The toxic effects on the stria vascularis of treatment with cisplatin alone and combined with the aminoglycoside antibiotic, gentamicin, were studied in guinea pigs. The toxicity induced in albino and pigmented guinea pigs was investigated morphologically with light and transmission electron microscopy, and functionally by brainstem‐evoked response audiometry. The results of hearing thresholds were variable, ranging from no change in one ear in some of the animals to a hearing loss of 20 dB in one or both ears when treated with low‐dose cisplatin alone or in combination with gentamicin. Bilateral deafness resulted from high‐dose cisplatin combined with gentamicin. The combined treatment produced prominent structural damage in the stria vascularis. The results should be considered when aminoglycoside therapy is required in conjunction with cisplatin.

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 Bowmans 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.

Quantitative Analysis of Tight Junctions and the Uptake of 99mTc in Human Gliomas

The structural dimensions of capillary tight junctions and the uptake of 99mTc pertechnetate in human gliomas were studied. Quantitative analysis revealed a correlation between the uptake of radionuclides and the length of endothelial tight junctions. It is suggested that brain scintigraphy might be used for the selection of malignant brain tumors with altered tight junctions which might be accessible to chemotherapy with water-soluble agents.