Effect of coenzyme A on outer hair cells in cisplatin ototoxicity: functional and ultrastructural study.
The aim of this study was to use functional and morphological analyses to evaluate the protective effect of coenzyme A (CoA) in cisplatin-induced toxicity in outer hair cells (OHC). Three groups of 8 guinea pigs were used: control (group I), cisplatin-treated (group II) and cisplatin + CoA-treated (group III). In groups II and III, a single ototoxic dose of cisplatin (10 mg/kg) was injected intraperitoneally. Group III was co-treated with CoA (900 μg/kg per day for 7 consecutive days). Electrocochleography (ECoG) recordings were made before and after the 7-day treatment period in all groups. After ECoG on day 7, all animals were anesthetized and the cochleae were removed and fixed for ultrastructural analysis. Cell damage in OHC was observed with transmission electron microscopy. Cisplatin induced a significant increase in auditory thresholds (p<0.001) compared to group I (control). In contrast, group III (cisplatin + CoA) had significantly reduced thresholds (p<0.001) compared to the group treated with cisplatin alone (group II).We found no significant differences between the control group and animals co-treated with cisplatin and CoA. The electron microscopy findings in OHC were consistent with these results. Ultrastructural analysis of OHC in group II showed morphological indications of necrosis, i.e. cytoplasmic swelling and vacuolation, and mitochondrial swelling. In group III the cell morphology of OHC was preserved, with ultrastructural characteristics similar to the control group. In conclusion, co-treatment with cisplatin with CoA inhibited antineoplastic-induced cytotoxicity in OHC in a guinea pig model.
Department of Otorhinolaryngology, School of Medicine, University of Granada, Granada, Spain. franfer@ugr.es.|Institute of Neuroscience, Biomedical Research Centre, University of Granada, Granada, Spain.
Francisco
F
Fernández-Cervilla
Department of Otorhinolaryngology, School of Medicine, University of Granada, Granada, Spain.
María
M
Martínez-Martínez
Institute of Neuroscience, Biomedical Research Centre, University of Granada, Granada, Spain.|Department of Histology, School of Medicine, University of Granada, Granada, Spain.
Eduardo
E
Fernández-Segura
Institute of Neuroscience, Biomedical Research Centre, University of Granada, Granada, Spain.|Department of Histology, School of Medicine, University of Granada, Granada, Spain.
Francisco Javier
FJ
Cañizares-García
Department of Histology, School of Medicine, University of Granada, Granada, Spain.
Pascual Vicente
PV
Crespo-Ferrer
D000818:Animals; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects* / Q000502:physiology; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003065:Coenzyme A / Q000494:pharmacology*; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology*
D020011:Protective Agents; D002945:Cisplatin; D003065:Coenzyme A