[Amifostine otoprotection to cisplatin ototoxicity: a guinea pig study using otoacoustic emission distortion products (DPOEA) and scanning electron microscopy].
Cisplatin is an antineoplastic drug for cancer treatment in children and adults. The side effects of cisplatin ototoxicity are significant: irreversible bilateral hearing damage to high frequencies (4 kHz - 8 kHz). Reports recognize some drugs that are associated with cisplatin to obtain an otoprotector effect. The ototoxicity mechanisms of cisplatin are related to injury of hair cell oxidation mechanism, especially of outer hair cells.


OBJECTIVE
Using otoacoustic emissions distortion products (DPOEA) and scanning electron microscopy we intended to verify the action of amifostine, a radioprotective drug that has well known antioxidant characteristics and otoprotector effects to cisplatin injury.


METHODS
Experimental.


METHODS
We used an experimental guinea pig model. The study was performed as follows: group 1: 6 animals, 12 ears, cisplatin 8.0 mg/Kg/day (IP), 3 days. Group 2: 6 animals, 12 ears, amifostine 100 mg/Kg/day (IP) and after 90 minutes, cisplatin 8.0 mg/Kg/day (IP), 3 days and group 3: 3 animals, 6 ears, amifostine 100 mg/Kg/day (IP), 3 days.


RESULTS
DPOEA were present before and after treatment in groups 2 and 3. The normal cilium architecture of outer hair cells was supported in all cochlear turns in groups 2 and 3. We concluded that amifostine has a potential otoprotector effect against cisplatin ototoxicity and could be used in clinical trials.
Hyppolito
Miguel Angelo
MA
Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo.
de Oliveira
Antonio A
AA
Lessa
Ricardo Miranda
RM
Rossato
Maria
M
D004999:Amifostine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004347:Drug Interactions; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000188:drug therapy; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D004999:Amifostine; D002945:Cisplatin