Teplova 2017 Toxicol Lett

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Teplova VV, Belosludtsev KN, Kruglov AG (2017) Mechanism of triclosan toxicity: Mitochondrial dysfunction including complex II inhibition, superoxide release and uncoupling of oxidative phosphorylation. Toxicol Lett 275:108-17.

» PMID: 28478158

Teplova VV, Belosludtsev KN, Kruglov AG (2017) Toxicol Lett

Abstract: Triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol), a widely used antibacterial agent, exerts adverse effects on the organism of mammals. Recent research revealed that triclosan at low micromolar concentrations causes mitochondrial dysfunction in many cell types, but the mechanisms of its effect are not fully understood. Here we show that exposure to triclosan disrupted membrane potential, prevented the calcium uptake-driven high-amplitude mitochondrial swelling, stimulated the respiration in the presence of complex I substrates, and suppressed the ADP-stimulated respiration in the presence of complex II substrate, succinate. Triclosan directly inhibited complex II activity. Similar to the complex II inhibitor thenoyltrifluoroacetone, triclosan induced the oxidation of the cytochromes b566 and b562 and caused the release of mitochondrial superoxide. Opposite to thenoyltrifluoroacetone, triclosan increased superoxide release synergistically with myxothiazol but not with antimycin A, indicating different topology of superoxide-producing sites. We concluded that triclosan is unique by its capability of acting as both a protonophore and an unusual complex II inhibitor, which interferes with the mitochondrial respiration by blocking the electron transfer between ubiquinone at the Qd-binding site and heme b. Our data can provide an insight into the mechanisms of the carcinogenic effect of triclosan in the liver and other tissues.

Copyright © 2017 Elsevier B.V. All rights reserved.

Keywords: Complex II inhibitor, Mitochondria, Q(d)-binding site, Superoxide anion, Triclosan, Uncoupler Bioblast editor: Kandolf G

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 

Regulation: Uncoupler  Coupling state: LEAK, OXPHOS  Pathway: N, S, CIV  HRR: Oxygraph-2k