The protective mechanism of antioxidants in cadmium-induced ototoxicity in vitro and in vivo.

Abstract

BACKGROUND:

Several heavy metals have been shown to have toxic effects on the peripheral and central auditory system. Cadmium (Cd2+) is an environmental contaminant showing a variety of adverse effects. Given the current rate of release into the environment, the amount of Cd2+ present in the human body and the incidence of Cd2+-related diseases are expected to increase.

OBJECTIVE:

The overall aim of this study was to gain further insights into the mechanism of Cd2+-induced ototoxicity.

METHODS:

Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse cochlea after Cd2+ exposure were measured by flow cytometry, immunohistochemical staining, Western blot analysis, and auditory brainstem response (ABR) recording. Mechanisms underlying Cd2+ototoxicity were studied using inhibitors of different signaling pathways, caspases, and antioxidants.

RESULTS:

Cd2+ exposure caused cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK activation, apoptosis, and finally auditory threshold shift. Cd2+ toxicity interfered with inhibitors of cellular signaling pathways, such as ERK and c-jun N-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase-9 and caspase-3. The antioxidants N-acetyl-l-cysteine and ebselen showed a significant protective effect on the Cd2+ toxicity.

CONCLUSIONS:

Cd2+ is ototoxic with a complex underlying mechanism. However, ROS generation may be the cause of the toxicity, and application of antioxidants can prevent the toxic effect.

• Authors: Su-Jin Kim, Hyun-Ja Jeong, Noh-Yil Myung, Min-chol Kim, Jeong-Han Lee, Hong-seob So, Rae-Kil Park, Hyung-Min Kim, Jae-Young Um, Seung-Heon Hong
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 116 Issue 7 Pg. 854-62 (Jul 2008) ISSN: 0091-6765 [Print] United States
• PMID: 18629305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Environmental Pollutants
• Reactive Oxygen Species
• Cadmium
• Caspases
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Cadmium (toxicity)
• Caspases (metabolism)
• Cell Line
• Cell Survival (drug effects)
• Cochlear Diseases (chemically induced, pathology, physiopathology)
• Environmental Pollutants (toxicity)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Organ of Corti (drug effects, pathology)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)