Adem Bora1, Kasım Durmuş1, Hatice Terzi2, Emine Elif Altuntaş1. 1. Department of Otolaryngology, Cumhuriyet University School of Medicine, Sivas, Turkey. 2. Department of Internal Medicine, Cumhuriyet University School of Medicine, Sivas, Turkey.
Abstract
OBJECTIVES: Nilotinib has very few side effects, including neutropenia, thrombocytopenia, cardiotoxicity, high pancreatic lipase, ischemia, and vascular occlusion. We aimed to investigate whether short-term administration of nilotinib had ototoxic effects in rats. MATERIALS AND METHODS: Wistar-albino rats were categorized into three groups: group C (administered 0.25 mL of distilled water, no nilotinib), group N-20 (administered 20 mg/kg/day of nilotinib dissolved in distilled water), and group N-50 (administered 50 mg/kg/day of nilotinib dissolved in distilled water). A single dose was administered once per day, at the same hour, over 21 days. Auditory brainstem response (ABR) thresholds were recorded on day 0 and day 21. RESULTS: There were no changes in ABR threshold values obtained on day 0 (baseline) and on day 21 across all three groups. A statistically significant difference was not found in terms of the mean latency of waves V and III, interpeak latency values of waves III-V, and amplitude ratios of waves III-V and V/Va at baseline and on day 21 across all three groups on within-group or between-group evaluation. CONCLUSION: Consequently, further studies are needed that involve different drug doses, prolonged administration of drugs, as well as distortion otoacoustic emission test for the evaluation of cochlear activation and ABR. Furthermore, histopathological studies are needed to indicate whether the cochlea is affected to prove that nilotinib has definitively no ototoxic effect.
OBJECTIVES: Nilotinib has very few side effects, including neutropenia, thrombocytopenia, cardiotoxicity, high pancreatic lipase, ischemia, and vascular occlusion. We aimed to investigate whether short-term administration of nilotinib had ototoxic effects in rats. MATERIALS AND METHODS: Wistar-albino rats were categorized into three groups: group C (administered 0.25 mL of distilled water, no nilotinib), group N-20 (administered 20 mg/kg/day of nilotinib dissolved in distilled water), and group N-50 (administered 50 mg/kg/day of nilotinib dissolved in distilled water). A single dose was administered once per day, at the same hour, over 21 days. Auditory brainstem response (ABR) thresholds were recorded on day 0 and day 21. RESULTS: There were no changes in ABR threshold values obtained on day 0 (baseline) and on day 21 across all three groups. A statistically significant difference was not found in terms of the mean latency of waves V and III, interpeak latency values of waves III-V, and amplitude ratios of waves III-V and V/Va at baseline and on day 21 across all three groups on within-group or between-group evaluation. CONCLUSION: Consequently, further studies are needed that involve different drug doses, prolonged administration of drugs, as well as distortion otoacoustic emission test for the evaluation of cochlear activation and ABR. Furthermore, histopathological studies are needed to indicate whether the cochlea is affected to prove that nilotinib has definitively no ototoxic effect.
Authors: Hagop M Kantarjian; Andreas Hochhaus; Giuseppe Saglio; Carmino De Souza; Ian W Flinn; Leif Stenke; Yeow-Tee Goh; Gianantonio Rosti; Hirohisa Nakamae; Neil J Gallagher; Albert Hoenekopp; Rick E Blakesley; Richard A Larson; Timothy P Hughes Journal: Lancet Oncol Date: 2011-08-17 Impact factor: 41.316
Authors: T D Kim; D Rea; M Schwarz; P Grille; F E Nicolini; G Rosti; L Levato; F J Giles; H Dombret; T Mirault; H Labussière; R Lindhorst; W Haverkamp; I Buschmann; B Dörken; P D le Coutre Journal: Leukemia Date: 2013-03-05 Impact factor: 11.528