1. Dibromoacetic Acid Induced Hepatotoxicity in Mice through Oxidative Stress and Toll-Like Receptor 4 Signaling Pathway Activation.
- Author
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Gong T, Jiang W, Gao Z, Chen Y, and Gao S
- Subjects
- Administration, Oral, Animals, Body Weight drug effects, Glutathione metabolism, Interleukin-1beta genetics, Interleukin-1beta metabolism, JNK Mitogen-Activated Protein Kinases genetics, JNK Mitogen-Activated Protein Kinases metabolism, Liver drug effects, Liver ultrastructure, Mice, Mice, Inbred BALB C, Myeloid Differentiation Factor 88 genetics, Myeloid Differentiation Factor 88 metabolism, NF-KappaB Inhibitor alpha genetics, NF-KappaB Inhibitor alpha metabolism, Reactive Oxygen Species metabolism, Toll-Like Receptor 4 metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Acetates toxicity, Liver metabolism, Oxidative Stress drug effects, Signal Transduction drug effects
- Abstract
Dibromoacetic acid (DBA) is one of haloacetic acids, often as a by-product of disinfection in drinking water. DBA is a multiple-organ carcinogen in rodent animals, but little research on its hepatotoxicity has been conducted and its mechanism has not been elucidated. In this study, we found that DBA could induce obvious hepatotoxcity in Balb/c mice as indicated by histological changes, increasing serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and accumulation of hepatic glycogen, after the mice were administered DBA at doses of 1.25, 5, and 20 mg/kg body weight for 28 days via oral gavage. In mechanism study, DBA induced oxidative stress as evidenced by increasing the level of malondialdehyde (MDA), reactive oxygen species (ROS) in the liver, advanced oxidative protein products (AOPPs) in the serum, and decreasing the level of glutathione (GSH) in the liver. DBA induced inflammation in the liver of the mice which is supported by increasing the production of tumor necrosis factor- α (TNF- α ) and the mRNA levels of TNF- α , interleukin-6 (IL-6), interleukin-1 β (IL-1 β ), and nuclear factor κ B (NF- κ B) in the liver. DBA also upregulated the protein levels of Toll-like receptor (TLR) 4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor κ B alpha (I κ B- α ), nuclear factor κ B p65 (NF- κ B p65), and the phosphoralation of P38 mitogen-activated protein kinase (P38MAPK) and c-Jun N-terminal kinase (JNK). Conclusion . DBA could induce hepatotoxicity in mice by oral exposure; the mechanism is related to oxidative stress, inflammation, and Toll-like receptor 4 signaling pathway activation., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Tingting Gong et al.)
- Published
- 2019
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