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Sathiyaseelan Theneshkumar, Guiscardo Lorito, Pietro Giordano, Joseph Petruccelli, Alessandro Martini, Stavros Hatzopoulos
Med Sci Monit 2009; 15(7): BR173-177
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.
Material and Method: 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.