Pyridoxine Preferentially Induces Auditory Neuropathy Through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress-Mediated Apoptosis.

Abstract

OBJECTIVES:

Auditory neuropathy due to toxicity mechanism of pyridoxine has not yet been fully documented. Therefore, the present study explored a direct mechanism underlying the effects of pyridoxine on auditory neuropathy in organ of Corti (OC) explants ex vivo and cochlear neuroblast cell line, VOT-33 in vitro.

METHODS:

Primary OC explants containing spiral ganglion neurons and cultured VOT-33 cells were treated with pyridoxine.

RESULTS:

In nerve fiber of primary OC explants, pyridoxine decreased staining for NF200, a neuro-cytoskeletal protein. We also found that pyridoxine-induced VOT-33 apoptosis, as indicated by accumulation of the sub-G0/G1 fraction, caspase-3 activation, and PARP cleavage. In addition, pyridoxine induced reactive oxygen species (ROS) generation and alteration of mitochondrial membrane potential transition (MPT), including Bcl-2 family protein expression and consequently Ca2+ accumulation and changes of endoplasmic reticulum (ER) stress-related protein expression such as phospho-PERK, caspase-12, Grp78, and CHOP.

CONCLUSION:

Pyridoxine preferentially induced severe cell death on nerve fiber in primary OC explants and markedly increased apoptotic cell death via mitochondria-mediated ER stress in VOT-33 cells.

• Authors: Channy Park, Hyewon Lim, Sung K Moon, Raekil Park
• Journal: The Annals of otology, rhinology, and laryngology (Ann Otol Rhinol Laryngol) Vol. 128 Issue 6_suppl Pg. 117S-124S (Jun 2019) ISSN: 1943-572X [Electronic] United States
• PMID: 31092035 (Publication Type: Journal Article)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• Hspa5 protein, mouse
• Vitamin B Complex
• Pyridoxine

Topics

• Animals
• Apoptosis (drug effects)
• Cell Culture Techniques
• Cell Line
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Hearing Loss, Central (etiology)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Organ of Corti (drug effects, pathology)
• Pyridoxine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vitamin B Complex (pharmacology)