92 - Chronic Lead Exposure Induces Cochlear Oxidative Stress and Impairs Hearing

Abstract

Oxidative stress plays a pivotal role in mediating hearing loss induced by exposure to a number of environmental risk factors. Elevated levels of lead is one of the commonly encountered risk factor in the urban environment. Though lead exposure damages the sensory, vascular, and neuronal components of the cochlea, it is not known whether oxidative stress mediates its ototoxic effects. The aim of this study is to delineate the redox mechanism underlying lead-induced auditory dysfunction. Young-adult C57BL/6 mice were exposed to: 1) control conditions or 2) 2 mM lead acetate in drinking water for 28 days. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS), lead-induced cochlear oxidative stress was assessed using targeted gene arrays, and hearing thresholds were assessed by recording auditory brainstem responses. Lead exposure significantly increased the blood lead levels to 293 ± 67 ppb. However, the body weight, appearance, and behavior of the lead-exposed mice were similar to that of the controls. This suggested that the exposure level was probably moderate for young-adult mice, and was not capable of inducing severe toxic effects. Nevertheless, lead exposure at this level downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. In addition, exposure to lead induced 8-12 dB shifts in hearing thresholds. Collectively, these findings suggest that chronic exposure to even moderate levels of lead induces cochlear oxidative stress and causes hearing loss.