Lead exposure results in hearing loss and disruption of the cochlear blood–labyrinth barrier and the protective role of iron supplement

• Pb2+ exposure resulted in hearing loss and damage of outer hair cells.
• Pb2+ exposure increased the permeability of the blood–labyrinth barrier.
• Pb2+ down-regulated the levels of occludin, ZO-1 and claudin-5 in the stria vascularis.
• Fe2+ supplement partly reversed the Pb2+-induced hearing loss and the disruption of BLB.

This study was designed to investigate the impact of lead (Pb2+) on the auditory system and its molecular mechanisms. Pb(AC)2 was administrated to male SD rats aged 21–22 d for 8 weeks at a dose of 300 ppm. Male guinea pigs were also administrated with 50 mg/kg Pb(AC)2 two times a week for 8 weeks. The auditory nerve–brainstem evoked responses (ABR) was recorded and the morphological changes of the outer hair cells (OHCs) were observed with Phallodin-FITC staining. In addition, the integrity of the blood–labyrinth barrier was observed by TEM and the expression of tight junction proteins (TJPs) in the cochlear stria vascularis was determined by immunofluorescence. Our results showed that Pb2+ exposure resulted in increased ABR threshold in both rats and guinea pigs. Abnormal shapes and loss of OHCs were found in the cochlear basilar membrane following the Pb2+ exposure. TEM study showed that the tight junctions between the endothelial cells and the border cells were lost and disrupted. Down-regulation of the occludin, ZO-1 and claudin-5 in the stria vascularis suggested that the increased permeability of the blood–labyrinth barrier may attribute to the Pb2+-induced decrease of TJPs’ expression. Additionally, Fe2+ supplement partly reversed the Pb2+-induced hearing loss and down-regulation of TJPs. Taken together, these data indicate that the disruption of blood–labyrinth barrier by down-regulating the expression of TJPs plays a role in the Pb2+-induced hearing loss, and Fe2+ supplement protects the auditory system against Pb2+-induced toxicity and may have significant clinical implications.