Protective effects of acetyl-L-carnitine on cisplatin cytotoxicity and oxidative stress in neuroblastoma.
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 ELISA(PLUS) 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 micromol 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.
Altun
Zekiye Sultan
ZS
Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Inciralti, 35340, Izmir, Turkey. zekiye.altun@deu.edu.tr
Güneş
Dilek
D
Aktaş
Safiye
S
Erbayraktar
Zübeyde
Z
Erbayrktar
Zübeyde
Z
Olgun
Nur
N
D000108:Acetylcarnitine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004396:Coloring Agents; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D004396:Coloring Agents; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D016271:Proto-Oncogene Proteins c-myc; D013778:Tetrazolium Salts; D013844:Thiazoles; D000108:Acetylcarnitine; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D005978:Glutathione; D002945:Cisplatin