Effect of noise conditioning on cisplatin-induced ototoxicity: a pilot study.
BACKGROUND
Cisplatin is a platinum-based chemotherapeutic agent that is highly effective in the treatment of cancer. Ototoxicity is an important dose-limiting adverse effect of cisplatin, in addition to nephrotoxicity. Studies have shown that cisplatin-induced ototoxicity is mainly a result of generated reactive oxygen species. Sulfur-containing compounds such as L-N acetylcysteine (L-NAC) and D-methionine (D-MET) have shown promising results as potent otoprotectors against cisplatin-induced ototoxicity in animal studies.


METHODS
In this study, we investigated a method to increase the efficacy of L-NAC and D-MET without increasing dose. Sprague Dawley rats were noise conditioned for 15 minutes immediately after intraperitoneal injection of 275 mg/kg L-NAC or 300 mg/kg D-MET. Another set of rats received 275 mg/kg L-NAC or 300 mg/kg D-MET alone, and 1 group underwent noise conditioning alone. All 5 groups were administered 14 mg/kg cisplatin intravenously 1 hour after otoprotector injection or 45 minutes after noise conditioning.


RESULTS
Otoprotectors and noise conditioning, alone or in combination, were analyzed for their ability to reduce cisplatin-induced ototoxicity. The results indicated that the combination of 275 mg/kg L-NAC and noise conditioning afforded more otoprotection than 275 mg/kg L-NAC alone. In the case of D-MET, 300 mg/kg plus noise conditioning was little better than 300 mg/kg D-MET alone. In addition, we found that noise conditioning alone showed otoprotection against cisplatin-induced ototoxicity.


CONCLUSIONS
The ability of noise conditioning to protect against cisplatin-induced ototoxicity requires additional study.
Theneshkumar
Sathiyaseelan
S
Department of Audiology, University of Ferrara, Ferrara, Italy. sdh1@unife.it
Lorito
Guiscardo
G
Giordano
Pietro
P
Petruccelli
Joseph
J
Martini
Alessandro
A
Hatzopoulos
Stavros
S
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D034381:Hearing Loss / Q000139:chemically induced*; D008297:Male; D009622:Noise / Q000009:adverse effects*; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D015431:Weight Loss / Q000187:drug effects
D002945:Cisplatin