Protective Effects of Melatonin and Alpha Lipoic Acid Against Cisplatin-Induced Ototoxicity

ABSTRACT
Aim: To investigate the potential protective effects of melatonin and alpha-lipoic acid against cisplatin-induced ototoxicity in a rat model using brainstem auditory evoked potentials.
Materials and Methods: Sixty Sprague-Dawley rats were randomly divided into six groups: control, cisplatin-only, melatonin-only, alpha-lipoic acid-only, cisplatin+melatonin, and cisplatin+alpha-lipoic acid. Cisplatin was administered as a single intraperitoneal injection (10 mg/kg). Melatonin (4 mg/kg) and alpha-lipoic acid (100 mg/kg) were administered daily for eight days, starting one day before cisplatin. Brainstem Auditory Evoked Potentials were measured at baseline and on days 3, 7, and 15. Wave latencies, interpeak latencies, hearing thresholds, and waveform morphology were analyzed.
Results: Cisplatin administration resulted in significant prolongation of wave V latency and increased hearing thresholds. Melatonin treatment significantly mitigated cisplatin-induced changes in wave V latency and hearing thresholds compared to cisplatin alone (p<0.05). Alpha-lipoic acid did not demonstrate significant protection against cisplatin-induced changes. Both melatonin and alpha-lipoic acid groups showed alterations in wave latencies when administered alone. Waveform distortions were most prevalent in the cisplatin group, with lower incidence in melatonin and alpha-lipoic acid treatment groups.
Conclusions: Treatment with melatonin significantly mitigates cisplatin-induced ototoxicity in rats, likely due to its potent antioxidant properties. This finding supports the potential of melatonin as a therapeutic strategy to prevent or minimize hearing loss in patients receiving cisplatin chemotherapy. However, alpha-lipoic acid did not exhibit significant protection in this study, warranting further investigation.
Keywords: Cisplatin, ototoxicity, melatonin, alpha-lipoic acid, antioxidants