title: Thimerosal induces apoptotic and fibrotic changes to kidney epithelial cells in vitro.
abstract: Thimerosal is an ethyl mercury-containing compound used mainly in vaccines as a bactericide. Although the kidney is a key target for mercury toxicity, thimerosal nephrotoxicity has not received the same attention as other mercury species. The aim of this study was to determine the potential cytotoxic mechanisms of thimerosal on human kidney cells. Human kidney proximal tubular epithelial (HK2) cells were exposed for 24 h to thimerosal (0-2 µM), and assessed for cell viability, apoptosis, and cell proliferation; expression of proteins Bax, nuclear factor-κB subunits, and transforming growth factor-β1 (TGFβ1); mitochondrial health (JC-1, MitoTracker Red CMXRos); and fibronectin levels (enzyme-linked immunosorbent assay). Thimerosal diminished HK2 cell viability and mitosis, promoted apoptosis, impaired the mitochondrial permeability transition, enhanced Bax and TGFβ1 expression, and augmented fibronectin secretion. This is the first report about kidney cell death and pro-fibrotic mechanisms promoted by thimerosal. Collectively, these in vitro results demonstrate that (1) thimerosal induces kidney epithelial cell apoptosis via upregulating Bax and the mitochondrial apoptotic pathway, and (2) thimerosal is a potential pro-fibrotic agent in human kidney cells. We suggest that new evidence on toxicity as well as continuous surveillance in terms of fibrogenesis is required concerning thimerosal use.
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Kent Street, Woolloongabba, Brisbane, Queensland, Australia.|Laboratório de Toxicologia e Essencialidade de Metais, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Do Café, s/n, Monte Alegre, Ribeirão Preto, SP, Brazil.
authors.forename: Maria Fernanda Hornos
authors.initials: MF
authors.lastname: Carneiro
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Kent Street, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Christudas
authors.initials: C
authors.lastname: Morais
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Kent Street, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Small
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Kent Street, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Vesey
authors.affiliation: Laboratório de Toxicologia e Essencialidade de Metais, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Do Café, s/n, Monte Alegre, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
authors.affiliation: Centre for Kidney Disease Research, School of Medicine, University of Queensland, Translational Research Institute, Kent Street, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D013849:Thimerosal / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D005353:Fibronectins; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D013849:Thimerosal
keywords: apoptosis; ethyl mercury; fibrosis; kidney; mitochondrial dysfunction; thimerosal; toxicity