RRC ID 58583
著者 Vitoux MA, Kessal K, Melik Parsadaniantz S, Claret M, Guerin C, Baudouin C, Brignole-Baudouin F, Réaux-Le Goazigo A.
タイトル Benzalkonium chloride-induced direct and indirect toxicity on corneal epithelial and trigeminal neuronal cells: proinflammatory and apoptotic responses in vitro.
ジャーナル Toxicol Lett
Abstract Benzalkonium chloride (BAK), a quaternary ammonium compound widely used as disinfecting agent as well as preservative in eye drops is known to induce toxic effects on the ocular surface with inflammation and corneal nerve damage leading to dry eye disease (DED) in the medium-to-long term. The aim of this study was to evaluate in vitro the toxicity of a conditioned medium produced by corneal epithelial cells previously exposed to BAK (BAK-CM) on trigeminal neuronal cells. A human corneal epithelial (HCE) cell line was exposed to 5.10-3% BAK (i.e. 0.005% BAK) for 15 min and let recover for 5 h to prepare a BAK-CM. This BAK concentration is the lowest one found in eye drops. After this recovery period, BAK effect on HCE cells displayed cytotoxicity, morphological alteration, apoptosis, oxidative stress, ATP release, CCL2 and IL6 gene induction, as well as an increase in CCL2, IL-6 and MIF release. Next, a mouse trigeminal ganglion primary culture was exposed to the BAK-CM for 2 h, 4 h or 24 h. Whereas BAK-CM did not alter neuronal cell morphology, or induced neuronal cytotoxicity or oxidative stress, BAK-CM induced gene expression of Fos (neuronal activation marker), Atf3 (neuronal injury marker), Ccl2 and Il6 (inflammatory markers). Two and 4 h BAK-CM exposure promoted a neuronal damage (ATF-3, phospho-p38 increases; phospho-Stat3 decreases) while 24 h-BAK-CM exposure initiated a prosurvival pathway activation (phospho-p44/42, phospho-Akt increases; ATF-3, GADD153, active Caspase-3 decreases). In conclusion, this in vitro model, simulating paracrine mechanisms, represents an interesting tool to highlight the indirect toxic effects of BAK or any other xenobiotic on corneal trigeminal neurons and may help to better understand the cellular mechanisms that occur during DED pathophysiology.
巻・号 319
ページ 74-84
公開日 2020-2-1
DOI 10.1016/j.toxlet.2019.10.014
PII S0378-4274(19)30333-9
PMID 31707104
MeSH Activating Transcription Factor 3 / biosynthesis Activating Transcription Factor 3 / drug effects Animals Apoptosis / drug effects* Benzalkonium Compounds / toxicity* Cell Line Dry Eye Syndromes / chemically induced Dry Eye Syndromes / pathology Epithelial Cells / drug effects* Epithelium, Corneal / cytology Epithelium, Corneal / drug effects* Gene Expression / drug effects Humans Inflammation / chemically induced* Inflammation / pathology Male Mice Mice, Inbred C57BL Neurons / drug effects* Oxidative Stress / drug effects Preservatives, Pharmaceutical / toxicity* Signal Transduction / drug effects Trigeminal Ganglion / cytology Trigeminal Ganglion / drug effects*
IF 3.499
リソース情報
ヒト・動物細胞 HCE-T(RCB2280)