L-N-acetyl-cysteine protection against cisplatin-induced auditory neuronaland hair cell toxicity

Objectives: The aim of this study is to determine the efficacy of L-N-acety l-cysteine (L-NAC) as a protectant for inner ear auditory sensory cells aga inst the toxic effects of cisplatin, Study Design: Prospective laboratory s tudy of the otoprotective effect of L-NAC on auditory neurons and hair cell s in vitro, Methods: The study has two arms. The first arm evaluated the ne uroprotective effect of L-NAC on early postpartum auditory ganglion cell cu ltures, Two culture media were used. The two media differed in that one of them was enhanced by the addition of neurotrophins (neurotrophin type 3 and brain-derived neurotrophic factor) and a growth factor (transforming growt h factor-pr). Then the survival of cisplatin-treated auditory neurons was s tudied before and after pretreatment with protective levels of L-NAC, The s econd arm of the study evaluated the effect of L-NAC on cisplatin damage in itiated to auditory hair cells. Early-postpartum organ of Corti explants we re grown in culture. Their rate of survival was studied after exposure to t oxic levels of cisplatin, Then, survival of cisplatin-damaged hair cells wa s studied after they were pretreated with L-NAC, Results: Pretreatment of c ultures with L-NAC protected both auditory newtons and hair cells from the effects of exposure to toxic levels of cisplatin, This observed otoprotecti ve effect was dose dependent. Conclusions: Our in vitro studies have demons trated that L-NAC protected both auditory neurons and hair cells from the t oxic effects of cisplatin. Because it protects both of these inner ear stru ctures, L-NAC may be potentially useful in protecting hearing, in general, from cisplatin-induced damage, In addition, L-NAC has low systemic and muco sal toxicity. It also has a low molecular weight that may allow it to readi ly cross the round window membrane. Ah these characteristics make it potent ially suitable for transtympanic application for the prevention of the otot oxicity of cisplatin in vivo.