α-Amanitin aggravates hepatic injury by activating oxidative stress and mitophagy via peroxiredoxin 6 inhibition

Siegert MJ, Knittel CH, Sussmuth RD. A convergent total synthesis of the death cap toxin alpha-amanitin. Angew Chem Int Ed Engl. 2020;59:5500–4. https://doi.org/10.1002/anie.201914620.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Garcia J, Costa VM, Carvalho A, et al. Amanita phalloides poisoning: Mechanisms of toxicity and treatment. Food Chem Toxicol. 2015;86:41–55. https://doi.org/10.1016/j.fct.2015.09.008.

Article  CAS  PubMed  Google Scholar 

Garcia J, Carvalho AT, Dourado DF, Baptista P, de Lourdes Bastos M, Carvalho F. New in silico insights into the inhibition of RNAP II by alpha-amanitin and the protective effect mediated by effective antidotes. J Mol Graph Model. 2014;51:120–7. https://doi.org/10.1016/j.jmgm.2014.05.002.

Article  CAS  PubMed  Google Scholar 

Ergin M, Dundar ZD, Kilinc I, Colak T, Oltulu P, Girisgin AS. Alpha-amanitin poisoning, nephrotoxicity and oxidative stress: an experimental mouse model. Iran Red Crescent Med J. 2015;17:e28068. https://doi.org/10.5812/ircmj.28068.

Article  PubMed  PubMed Central  Google Scholar 

Chen X, Shao B, Yu C, et al. Energy disorders caused by mitochondrial dysfunction contribute to alpha-amatoxin-induced liver function damage and liver failure. Toxicol Lett. 2021;336:68–79. https://doi.org/10.1016/j.toxlet.2020.10.003.

Article  CAS  PubMed  Google Scholar 

Chen X, Shao B, Yu C, et al. The cyclopeptide <alpha>-amatoxin induced hepatic injury via the mitochondrial apoptotic pathway associated with oxidative stress. Peptides. 2020;129:170314. https://doi.org/10.1016/j.peptides.2020.170314.

Article  CAS  PubMed  Google Scholar 

Jomova K, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M. Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol. 2024;98:1323–67. https://doi.org/10.1007/s00204-024-03696-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou XR, Wang XY, Sun YM, et al. Glycyrrhizin protects submandibular gland against radiation damage by enhancing antioxidant defense and preserving mitochondrial homeostasis. Antioxid Redox Signal. 2024. https://doi.org/10.1089/ars.2022.0183.

Article  PubMed  Google Scholar 

Zhang Q, Hu Y, Hu JE, et al. Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. Life Sci. 2021;278:119529. https://doi.org/10.1016/j.lfs.2021.119529.

Article  CAS  PubMed  Google Scholar 

Jia G, Tan B, Ma J, Zhang L, Jin X, Li C. Prdx6 upregulation by curcumin attenuates ischemic oxidative damage via SP1 in rats after stroke. Biomed Res Int. 2017;2017:6597401. https://doi.org/10.1155/2017/6597401.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mu R, Ye S, Lin R, Li Y, Guo X, An L. Effects of peroxiredoxin 6 and its mutants on the isoproterenol induced myocardial injury in H9C2 cells and rats. Oxid Med Cell Longev. 2022;2022:2576310. https://doi.org/10.1155/2022/2576310.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu Y, Wang S, Leung CK, et al. alpha-amanitin induces autophagy through AMPK-mTOR-ULK1 signaling pathway in hepatocytes. Toxicol Lett. 2023;383:89–97. https://doi.org/10.1016/j.toxlet.2023.06.004.

Article  CAS  PubMed  Google Scholar 

Kwon J, Wang A, Burke DJ, et al. Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration. Free Radic Biol Med. 2016;96:99–115. https://doi.org/10.1016/j.freeradbiomed.2016.04.009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fisher AB, Dodia C, Feinstein SI. Identification of Small Peptides that Inhibit NADPH Oxidase (Nox2) Activation. Antioxidants (Basel). 2018;7:181. https://doi.org/10.3390/antiox7120181.

Article  CAS  PubMed  Google Scholar 

Hervera A, De Virgiliis F, Palmisano I, et al. Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons. Nat Cell Biol. 2018;20:307–19. https://doi.org/10.1038/s41556-018-0039-x.

Article  CAS  PubMed  Google Scholar 

Zhao M, Wang Y, Li L, et al. Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance. Theranostics. 2021;11:1845–63. https://doi.org/10.7150/thno.50905.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moulton MJ, Barish S, Ralhan I et al. Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer’s disease-associated genes. Proc Natl Acad Sci U S A. 118 (2021) https://doi.org/10.1073/pnas.2112095118.

Ma S, Zhang X, Zheng L, et al. Peroxiredoxin 6 is a crucial factor in the initial step of mitochondrial clearance and is upstream of the PINK1-parkin pathway. Antioxid Redox Signal. 2016;24:486–501. https://doi.org/10.1089/ars.2015.6336.

Article  CAS  PubMed  Google Scholar 

Lopez-Grueso MJ, Lagal DJ, Garcia-Jimenez AF, et al. Knockout of PRDX6 induces mitochondrial dysfunction and cell cycle arrest at G2/M in HepG2 hepatocarcinoma cells. Redox Biol. 2020;37:101737. https://doi.org/10.1016/j.redox.2020.101737.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hsu SS, Lin YS, Chio LM, Liang WZ. Evaluation of the mycotoxin patulin on cytotoxicity and oxidative stress in human glioblastoma cells and investigation of protective effect of the antioxidant N-acetylcysteine (NAC). Toxicon. 2023;221:106957. https://doi.org/10.1016/j.toxicon.2022.106957.

Article  CAS  PubMed  Google Scholar 

Wang L, Xu Y, Zhao X, et al. Antagonistic effects of N-acetylcysteine on lead-induced apoptosis and oxidative stress in chicken embryo fibroblast cells. Heliyon. 2023;9:e21847. https://doi.org/10.1016/j.heliyon.2023.e21847.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alqahtani LS, Abd-Elhakim YM, Mohamed AA, et al. Curcumin-loaded chitosan nanoparticles alleviate fenpropathrin-induced hepatotoxicity by regulating lipogenesis and pyroptosis in rats. Food Chem Toxicol. 2023;180:114036. https://doi.org/10.1016/j.fct.2023.114036.

Article  CAS  PubMed  Google Scholar 

Mahfouz H, Dahran N, Abdel-Rahman Mohamed A, et al. Stabilization of glutathione redox dynamics and CYP2E1 by green synthesized Moringa oleifera-mediated zinc oxide nanoparticles against acrylamide induced hepatotoxicity in rat model: Morphometric and molecular perspectives. Food Chem Toxicol. 2023;176:113744.

Article  CAS  PubMed  Google Scholar 

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–8. https://doi.org/10.1006/meth.2001.1262.

Article  CAS  PubMed  Google Scholar 

Chaikh A, Giraud JY, Perrin E, Bresciani JP, Balosso J. The choice of statistical methods for comparisons of dosimetric data in radiotherapy. Radiat Oncol. 2014;9:205. https://doi.org/10.1186/1748-717X-9-205.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang M, Chen Y, Guo Z, et al. Changes in the mitochondrial proteome in human hepatocytes in response to alpha-amanitin hepatotoxicity. Toxicon. 2018;156:34–40. https://doi.org/10.1016/j.toxicon.2018.11.002.

Article  CAS  PubMed  Google Scholar 

Arici MA, Sahin A, Cavdar Z, et al. Effects of resveratrol on alpha-amanitin-induced nephrotoxicity in BALB/c mice. Hum Exp Toxicol. 2020;39:328–37. https://doi.org/10.1177/0960327119888271.

Article  CAS  PubMed  Google Scholar 

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