title: Evaluation of the effect of acetyl L-carnitine on experimental cisplatin ototoxicity and neurotoxicity.
abstract: BACKGROUND
  Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent for pediatric tumors, and ototoxicity is one of the dose-limiting side effects.
  
  
  OBJECTIVE
  It was the aim of our study to investigate the effect of acetyl L-carnitine (ALCAR) on experimental CDDP ototoxicity by audiologic tests, histomorphologic, immunohistochemical and ultrastructural examinations and to investigate the apoptotic pathways.
  
  
  METHODS
  Wistar albino rats (n = 28) were studied. Baseline audiological tests were performed in 4 groups: group 1, control; group 2, ALCAR; group 3, CDDP; group 4, CDDP + ALCAR-administered rats. Control audiological tests were performed on the 3rd day, and then the rats were sacrificed. Ear and brain specimens were examined by transmission electron microscopy, and caspase 3, 8 and 9 activities were investigated.
  
  
  RESULTS
  The CDDP-administered rats showed significant auditory brainstem response threshold shifts using all stimuli (clicks, 6-kHz and 8-kHz tone burst) compared with the control groups. The CDDP + ALCAR-administered rats showed significant auditory brainstem response threshold shifts by only click stimuli compared with the control groups. In the brain, spiral ganglion and organ of Corti, ultrastructural damage was prominent in group 3; the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase 3, 8 and 9 immunostaining cells was significantly high in group 3.
  
  
  CONCLUSIONS
  ALCAR improves CDDP-induced auditory impairment, and also antioxidative and antiapoptotic properties of ALCAR on CDDP ototoxicity were supported by the findings.
authors.affiliation: Department of Pediatric Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey. dilek.gunes@deu.edu.tr
authors.forename: Dilek
authors.initials: D
authors.lastname: Gunes
authors.forename: Günay
authors.initials: G
authors.lastname: Kirkim
authors.forename: Efsun
authors.initials: E
authors.lastname: Kolatan
authors.forename: Enis Alpin
authors.initials: EA
authors.lastname: Guneri
authors.forename: Candan
authors.initials: C
authors.lastname: Ozogul
authors.forename: Zekiye
authors.initials: Z
authors.lastname: Altun
authors.forename: Bülent
authors.initials: B
authors.lastname: Serbetcioglu
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktas
authors.forename: Kamer
authors.initials: K
authors.lastname: Mutafoglu
authors.forename: Ozlem
authors.initials: O
authors.lastname: Tufekci
authors.forename: Zübeyde
authors.initials: Z
authors.lastname: Erbayraktar
authors.forename: Nur
authors.initials: N
authors.lastname: Olgun
mesh_terms: D000108:Acetylcarnitine / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001921:Brain / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects*; D004432:Ear, Middle / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D006198:Hair Cells, Auditory / Q000473:pathology / Q000648:ultrastructure; D006311:Hearing Disorders / Q000139:chemically induced; D009925:Organ of Corti / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D014803:Vitamin B Complex; D000108:Acetylcarnitine; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002945:Cisplatin