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      Astaxanthin mitigates cobalt cytotoxicity in the MG-63 cells by modulating the oxidative stress

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          Abstract

          Background

          With the re-popularity of metal-on-metal (MoM) bearing in recent years, the cobalt toxicity has been a cause for concern in the total hip replacement surgery by both physicians and patients.

          Methods

          MG-63 cell line was cultured in vitro and incubated with cobalt (II) chloride (CoCl 2) and/or with astaxanthin (ASX) for 24 h. MTT assay was conducted to evaluate the cell viability after cobalt exposure and ASX treatment. Fluorescence-activated cell sorting (FACS) analysis was performed to examine the reactive oxygen species (ROS) level. Quantitative real-time polymerase chain reaction (PCR) was adopted to determine the mRNA levels of related targets. And western blot analysis was used to examine the protein expressions. One-way ANOVA with posttest Newman-Keuls multiple comparisons was adopted to analysis all the obtained data.

          Results

          In the current study, ASX exhibited significant protective effect against the Co(II)-induced cytotoxicity in MG-63 cell line. We also found that ASX protected the cells against Co-induced apoptosis by regulating the expression of Bcl-2 family proteins. Besides, heme oxygenase 1 (HO-1) could be activated by Co exposure; ASX treatment significantly inhibited HO-1 activation, suppressing the oxidative stress induced by Co exposure. Moreover, c-Jun N-terminal Kinase (JNK) phosphorylation was shown to participate in the signaling pathway of the protective effect of ASX. However, knockdown of JNK expression by siRNA transfection or JNK inhibitor SP600125 treatment did not affect the protective effect of ASX against cobalt cytotoxicity in MG-63 cells.

          Conclusions

          ASX mitigated cobalt cytotoxicity in the MG-63 cells by modulating the oxidative stress. And ASX could be a promising therapy against cobalt toxicity in the hip articulation surgery.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s40360-017-0166-1) contains supplementary material, which is available to authorized users.

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          Most cited references40

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          Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.

          Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
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            TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.

            Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways. Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
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              Astaxanthin: a review of its chemistry and applications.

              Astaxanthin is a carotenoid widely used in salmonid and crustacean aquaculture to provide the pink color characteristic of that species. This application has been well documented for over two decades and is currently the major market driver for the pigment. Additionally, astaxanthin also plays a key role as an intermediary in reproductive processes. Synthetic astaxanthin dominates the world market but recent interest in natural sources of the pigment has increased substantially. Common sources of natural astaxanthin are the green algae Haematococcus pluvialis, the red yeast, Phaffia rhodozyma, as well as crustacean byproducts. Astaxanthin possesses an unusual antioxidant activity which has caused a surge in the nutraceutical market for the encapsulated product. Also, health benefits such as cardiovascular disease prevention, immune system boosting, bioactivity against Helycobacter pylori, and cataract prevention, have been associated with astaxanthin consumption. Research on the health benefits of astaxanthin is very recent and has mostly been performed in vitro or at the pre-clinical level with humans. This paper reviews the current available evidence regarding astaxanthin chemistry and its potential beneficial effects in humans.
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                Author and article information

                Contributors
                shanghaildh@hotmail.com
                tww944057350@sina.com
                liudh997@163.com
                zouym0771@163.com
                zhangchenshanghai@163.com
                +86 21 31161683 , weidongxu2016@yeah.net
                Journal
                BMC Pharmacol Toxicol
                BMC Pharmacol Toxicol
                BMC Pharmacology & Toxicology
                BioMed Central (London )
                2050-6511
                24 July 2017
                24 July 2017
                2017
                : 18
                : 58
                Affiliations
                [1 ]Department of Orthopedics, The Eighty-eighth Military Hospital, Tai’an, 271000 China
                [2 ]ISNI 0000 0004 0369 1599, GRID grid.411525.6, Department of Orthopedics, , Shanghai Changhai Hospital, Naval Medical University, ; Shanghai, 200433 China
                Author information
                http://orcid.org/0000-0002-9826-5765
                Article
                166
                10.1186/s40360-017-0166-1
                5525213
                28738843
                8d257d78-57e6-42be-ad61-3472db507cfe
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 December 2016
                : 14 July 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81171686
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Toxicology
                astaxanthin,mg-63 cells,cobalt cytotoxicity,oxidative stress
                Toxicology
                astaxanthin, mg-63 cells, cobalt cytotoxicity, oxidative stress

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