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KMID : 0350519950480010235
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Journal of Catholic Medical College
1995 Volume.48 No. 1 p.235 ~ p.246
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Ototoxicity of Carboplatin and Rescue Effect of Fosfomycin in Guinea Pig
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Abstract
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Cis-dichlorodiammineplatinum(cisplatin) is approved to have antineoplastic activity against cancers of testicles, ovaries and head and neck. But its clinical use is limited because of serious toxic side effects including ototoxicity and
nephrotoxicity.
Many trials have been made ot reduce this limitation such as hydration, mannitol diuresis and usage of rescue agent, but there are no adequate regimens.
In an attempt to reduce toxic effect of cisplatin a group of second generation platinum compounds were developed including carboplatin, The first clinical trial of the carboplatin which was originally thought to be free of ototoxicity or
nephrotoxicity
of cisplatin was introduced in 1981. However, in human clinical trials carboplatin appears considerably less toxic than cisplatin. To solve the adverse effect of carboplatin many rescue agents have been experimentally used.
The purpose of this study was to investigate carboplatin-induced ototoxicity and nephrotoxicity and protective effect of fosfomycin on the cochlear and kidney using auditory brainstem evoked response and light microscopic examination.
Fourth healthy guinea pigs, weighing 300 g to 400 g were devided into four groups : normal control group was given intraperitoneally with normal saline 2 ml (n=5) and intramuscularly with normal saline 1.5 ml(n=5). Fosfomycin-treated group was
given
intramuscularly with fosfomycin 320 mg/kg(N=10). Carboplatin-treated group was given intraperitoneally with carboplatin 40 mg/kg(n=10). Caboplatin and fosfomycin-treated group was given intramuscularly with fosfomycin 320 mg/kg and 30 minutes
later,
carboplatin 40 mg/kg was given intraperitonally(n=10).
@ES The results were as follows.
@EN 1. Auditory brainstem evoked response thresholds were 31 dB in normal control and fosfomycintreated group, 72 dB in carboplatin-treated group, 51 dB in carboplatin and fosfomycn-treated group, respectively.
2. In carboplatin-treated group degenerative changes of the hair cell were sporadically observed in outer hair cell, mainly in outer rows, of lower turns, There were no degenerative changes in inner hair cell.
In carboplatin and fosfomycin-treated group degenerative changes of hair cell were much decreased when they were compared with carboplatin-treated group and there were no degenerative changes in inner hair cell.
3. On microscopic examination of the kidney, carboplatin-treated group showed severe cystic dilatation of proximal renal tubules but carboplatin and fosfomycin-treated group demonstrated mild cystic dilatation of proximal renal tubules. No
degenerative
changes were noted in fosfomycin-treated group.
These results suggest that fosfomycin protect the carbopatin-induced ototoxicity and nephrotoxicity.
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