Original Paper

Neurochemical Research

, Volume 35, Issue 3, pp 437-443

First online:

Protective Effects of Acetyl-l-Carnitine on Cisplatin Cytotoxicity and Oxidative Stress in Neuroblastoma

  • Zekiye Sultan AltunAffiliated withDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylul University Email author 
  • , Dilek GüneşAffiliated withDepartment of Pediatric Oncology, Institute of Oncology, Dokuz Eylul University
  • , Safiye AktaşAffiliated withDepartment of Basic Oncology, Institute of Oncology, Dokuz Eylul University
  • , Zübeyde ErbayrktarAffiliated withIzmir Vocational School, Dokuz Eylul University
  • , Nur OlgunAffiliated withDepartment of Pediatric Oncology, Institute of Oncology, Dokuz Eylul University

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Abstract

The most widely used platinum-derived drug is cisplatin in neuroblastoma (NB) chemotherapy, which is severely neurotoxic. Acetyl-l-Carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms. The aim of this study was to determine the effects of ALC on cisplatin induced cytotoxicity and oxidative stress in NB cells. SH-SY5Y (N-Myc negative) and KELLY (N-Myc positive) human NB cell lines were used. Cisplatin induced apoptosis was assessed by using a Cell Death Detection ELISAPLUS kit. Lipid peroxidation levels were determined by HPLC analysis. Glutathione levels were determined spectrophotometrically. ALC was used prophylactic or after cisplatin application. The level of cisplatin doses were determined in both type of NB cells at which 50% cell death occurred along with synchronized apoptosis induced. Prophylactic 10 and 50 μmol of ALC concentrations were decreased cisplatin induced lipid peroxidation compared to controls that normally exhibited apoptosis especially in SH-SY5Y cells. Cisplatin caused oxidative stress through decreasing glutathione levels in both cell types. ALC were effectively inhibited the increase in cisplatin induced oxidized glutathione and lipid peroxidation formation in NB cells. We suggested that prophylactic ALC would be a useful agent for cisplatin induced toxicity in NB cells.

Keywords

Acetyl-l-carnitine Cisplatin toxicity Neuroblastoma Neuroprotection Apoptosis Oxidative stress