The effects of the antioxidant α-tocopherol succinate on cisplatin-induced ototoxicity in HEI-OC1 auditory cells.

Abstract

CONCLUSION:

D-α-tocopherol succinate significantly reduced a cisplatin-induced hair cell loss in HEI-OC1 cell lines. These effects were mediated by its scavenging activity against reactive oxygen species (ROS) and inhibition of apoptosis.

OBJECTIVES:

Alpha-tocopherol is a class of methylated phenols, known as fat-soluble antioxidants, and is a different form of vitamin E, which reduces free radicals and acts as an antioxidant. We hypothesized that the antioxidative effect of α-tocopherol could protect against cisplastin-induced cytotoxicity, and thus evaluated its effects on cisplatin-induced ototoxicity in HEI-OC1 auditory cells.

METHODS:

HEI-OC1 cells were pretreated with D-α-tocopherol succinate at a concentration of 10 µM for 24 h, and then exposed to 15 µM cisplatin for 48 h. The cellular viability was measured by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The intracellular ROS level was measured by using a fluorescent dye, 2',7'-dichlorofluorescein diacetate (DCFH-DA). Both Annexin V-FITC and propidium iodide (PI) staining were performed to analyze the pattern of apoptosis. The enzymatic activity of caspase-3 was assayed with caspase3/CPP32 fluorometric assay kit. Also, it was assessed by immunoblotting technique of poly-ADP-ribose polymerase (PARP).

RESULTS:

Pretreatment with 10 µM D-α-tocopherol succinate protected HEI-OC1 auditory cells against cisplatin-induced cytotoxicity. D-α-tocopherol succinate significantly reduced the cisplatin-induced increase in ROS. D-α-tocopherol succinate treatment induced a 15% reduction of ROS and 50% decrease in necrosis and late apoptosis as compared to cisplatin treatment. D-α-tocopherol succinate also decreased the activation of caspase-3 and reduced levels of cleaved poly-ADP-ribose polymerase (PARP).

• Authors: Sung Kyun Kim, Gi Jung Im, Yun Suk An, Se Hee Lee, Hak Hyun Jung, Sang Yoo Park
• Journal: International journal of pediatric otorhinolaryngology (Int J Pediatr Otorhinolaryngol) Vol. 86 Pg. 9-14 (Jul 2016) ISSN: 1872-8464 [Electronic] Ireland
• PMID: 27260571 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antioxidants
• Reactive Oxygen Species
• alpha-Tocopherol
• Cisplatin

Topics

• Antineoplastic Agents (toxicity)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Cisplatin (toxicity)
• Hair Cells, Auditory (drug effects, metabolism)
• Humans
• Reactive Oxygen Species (metabolism)
• alpha-Tocopherol (pharmacology)