title: Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines.
abstract: OBJECTIVE
  Cisplatin is an anti-neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl-L-carnitine would have protective effects on cisplatin-induced ototoxicity in vitro, and if present, to reveal roles of apoptotic gene expressions and pro-inflammatory cytokines.
  
  
  METHODS
  House Ear Institute-Organ of Corti 1 cell line was used for this study. Apoptotic genes were evaluated with an apoptosis PCR array and pro-inflammatory cytokine levels were measured using ELISA.
  
  
  RESULTS
  Apoptotic cell death reduced by around 22% with acetyl-L-carnitine-cisplatin treatment compared to cisplatin alone. Genes displaying increase in expression of apoptosis, related to cisplatin treatment, were Casp8, Bcl10, Bcl2, Bcl2l1, Bcl2l2, Bid, Naip1, Bnip3l, Card6, Pak7, Cd40, Trp 53inp1, Cideb and Cd70. The acetyl-L-carnitine-cisplatin combination caused reduced expression of genes Casp8, Fas, Casp1, Tnfrsf11b, Tnfrsf10b induced by cisplatin. Acetyl-L-carnitine-cisplatin also caused reduced levels of IL-6, IL-1β and TNF-α, pro-inflammatory cytokines, induced by cisplatin.
  
  
  CONCLUSIONS
  Protective mechanisms of aceytl-L-carnitine against cisplatin induced apoptosis, mainly due to activation of anti-apoptotic Bcl family members' genes, and in an Akt-related gene expression dependent manner. This is the first study to indicate that acetyl-L-carnitine can be an effective agent against cisplatin ototoxicity in auditory cells, with induction of anti-apoptotic gene expression and attenuating levels of pro-inflammatory cytokines.
authors.affiliation: Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, 35340, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Altun
authors.forename: Y
authors.initials: Y
authors.lastname: Olgun
authors.forename: P
authors.initials: P
authors.lastname: Ercetin
authors.forename: S
authors.initials: S
authors.lastname: Aktas
authors.forename: G
authors.initials: G
authors.lastname: Kirkim
authors.forename: B
authors.initials: B
authors.lastname: Serbetcioglu
authors.forename: N
authors.initials: N
authors.lastname: Olgun
authors.forename: E A
authors.initials: EA
authors.lastname: Guneri
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D004347:Drug Interactions; D051379:Mice; D009925:Organ of Corti / Q000166:cytology* / Q000276:immunology; D059467:Transcriptome / Q000187:drug effects; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D014803:Vitamin B Complex; D000108:Acetylcarnitine; D002945:Cisplatin