title: Lead exposure results in hearing loss and disruption of the cochlear blood-labyrinth barrier and the protective role of iron supplement.
abstract: This study was designed to investigate the impact of lead (Pb(2+)) 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 300ppm. Male guinea pigs were also administrated with 50mg/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 Pb(2+) 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 Pb(2+) 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 Pb(2+)-induced decrease of TJPs' expression. Additionally, Fe(2+) supplement partly reversed the Pb(2+)-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 Pb(2+)-induced hearing loss, and Fe(2+) supplement protects the auditory system against Pb(2+)-induced toxicity and may have significant clinical implications.
authors.affiliation: Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xinqin
authors.initials: X
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Wu
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Shen
authors.forename: Jinfei
authors.initials: J
authors.lastname: Jing
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Han
authors.initials: H
authors.lastname: Song
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Chen
authors.forename: Wenjing
authors.initials: W
authors.lastname: Luo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057167:Claudins / Q000378:metabolism; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004569:Electroencephalography; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000648:ultrastructure; D034381:Hearing Loss / Q000139:chemically induced*; D008297:Male; D046529:Microscopy, Electron, Transmission; D062793:Occludin / Q000378:metabolism; D009942:Organometallic Compounds / Q000097:blood / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D057167:Claudins; D062793:Occludin; D009942:Organometallic Compounds; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C008261:lead acetate
keywords: ABR; BBB; BCB; BLB; Blood–labyrinth barrier; Hearing loss; IHC; Lead; OHCs; Outer hair cells; TEM; TJPs; Tight junction proteins; auditory nerve–brainstem evoked responses; blood–brain barrier; blood–cerebrospinal fluid barrier; blood–labyrinth barrier; outer hair cells; sinner hair cells; tight junction proteins; transmission electron microscopy