Lead Induced Ototoxicity and Neurotoxicity in Adult Guinea Pig

Abstract

Lead exposure causes or aggravates hearing damage to human or animal, but the detailed effects of lead exposure on auditory system including injury sites of the cochlea in mammal remain controversy. To investigate the effect of chronic lead exposure on auditory system, 40 adult guinea pigs with normal hearing were randomly divided into five groups. They were fed 2 mmol/L lead acetate in drinking water for 0, 15, 30, 60, and 90 days (n = 8), respectively. Lead concentrations in blood, cochlea, and brainstem were measured. Auditory function was measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). The morphology of cochlea and brainstem was observed, and expression of autophagy-related protein in brainstem was also assessed. The blood lead concentration reached a high level at the 15th day and kept stable, but the lead level in brainstem and cochlear tissue increased obviously at the 60th day and 90th day of lead exposure, respectively. There was no significant difference in the morphology of hair cells and stria vascularis (SV) among these five groups, but the number of spiral ganglion neuron (SGN) gradually decreased after 60 days. The differences of ABR thresholds and DPOAE amplitudes were not statistically significant among each group, but I wave latency, III latency, and I-III wave interval of ABR were delayed with the prolonging of time of lead exposure. The expressions of autophagy-related protein ATG5, ATG6, and LC3B in brainstem were increased after 30 days. These results suggest that the key target of lead toxicity was the auditory nerve conduction pathway including SGNs and brainstem, rather than cochlear hair cells and SV. Autophagy may play a very important role in lead toxicity to auditory nervous system.

Effectiveness of hair lead concentration as biological indicator of environmental and professional exposure s

“…The stability of the hair as matrix and its direct interference with the environmental sources of exposure may be origin of the fluctuations in the results of some other studies [17]. The significant correlation between Pb-hair and Pb-blood suggests the efficiency and effectiveness of using hair for assessing occupational exposure specially in highly polluted areas [18][19][20].…”

Lead exposure induces nitrative stress and disrupts ribbon synapses in the cochlea

“…Although OHCs were not damaged, wave 1 latencies were prolonged in ABRs recorded post lead exposure ( Liu et al, 2011 ; Zhang et al, 2019 ), suggesting interference with the transmission of auditory signals potentially due to cochlear neuropathy. Several studies have reported that lead-induced neuronal damage is facilitated by glutamate excitotoxicity ( Lasley and Gilbert, 2002 ), excessive Ca 2 + influx ( Ferguson et al, 2000 ; Kern et al, 2000 ), and oxidative stress ( Ding et al, 2000 ; Patrick, 2006 ; Antonio-Garcia and Masso-Gonzalez, 2008 ), which are mechanisms attributed to cochlear synaptopathy and neurodegeneration of the auditory nerve ( Liberman and Kujawa, 2017 ; Sebe et al, 2017 ).…”

Nanomotor-based adsorbent for blood Lead(II) removal in vitro and in pig models

“…The Bama miniature pigs was used as experimental pigs (female, 50 kg, n = 3). Animal models of Pb(II) poisoning were established by feeding lead acetate (1.5 g day − 1 , 10 day) [ 47 ]. Pig of the control group was detoxified by oral DMSA (0.5 g day − 1 , 7 day) [ 48 ].…”