Wenying Chen , Shuangchao Liu , Yao Zhou , Bin Liu , Wei Wang , Cheng Chen , Zaixiang Lou , Xiao Li Shen
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引用次数: 0
Abstract
Perfluorohexane sulfonate (PFHxS), a common alternative to perfluorootane sulfonate, is extensively used in various industrial products. As PFHxS contamination becomes more prevalent, it has been detected in human umbilical cord blood, serum, and breast milk, among other samples. In humans, the elimination half-life of PFHxS is at least 8.5 years. Although PFHxS shows the highest tissue-plasma partition coefficients in the liver and is known to cause liver hypertrophy, the mechanisms underlying PFHxS-induced hepatotoxicity remain unclear. In present study, the impacts of PFHxS on human liver L02 cells were evaluated by examining cell viability, apoptotic rates, reactive oxygen species (ROS) levels, Ca2+ levels, and protein expressions. Results revealed that a 24-h exposure to PFHxS at concentrations of 80–320 μM, particularly at 320 μM, triggered autophagy and endoplasmic reticulum stress (ERS)-regulated mitochondrial pathway apoptosis. This was characterized by increased ROS and Ca2+ levels and upregulation of proteins such as LC3B-II, ATG3, ATG5, ATG7, p-Beclin-1, p62, ATF6, GRP78, CHOP, Bax, CYPD, and Cyt-C. Conversely, the protein expressions of Sigma-1 receptor (Sig-1R), p-mTOR, and Bcl-2 were inhibited. In conclusion, PFHxS induces liver cytotoxicity by activating autophagy and ERS-regulated mitochondrial pathway apoptosis. This study is the first to elucidate the mechanisms underlying PFHxS-induced liver cytotoxicity.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.