Projects per year
Abstract
Background and Aims: Pannexins (Panx) constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The pannexin family consists of 3 members of which Panx1 is expressed in the liver. It is well-known that Panx1 plays a key role in innate immunity by facilitating activation of the inflammasome. Recently, Panx1-mediated inflammation was found to be involved in non-alcoholic steatohepatitis in mouse. In the present study, it is investigated whether this also holds true for acute liver failure in casu triggered by acetaminophen.
Methods: Mice were overdosed with acetaminophen followed by treatment with the Panx1 channel inhibitor 10Panx1 after 1.5 hours. Sampling was performed 24 hours after acetaminophen administration. Evaluation of the effect of Panx1 channel inhibition was based on a number of clinically relevant read-outs, including assessment of alanine and aspartate aminotransferase serum levels as well as histopathological examination of liver tissue with quantification of cell death. Inflammation was studied by measurement of cytokine levels in liver and serum.
Results: All parameters measured indicate a significant reduction of liver damage, including cell death and inflammation, upon treatment of acetaminophen-intoxicated mice with 10Panx1.
Conclusions: The results of this study demonstrate the clinical potential of Panx1 channel inhibition as a therapeutic strategy in the treatment of acetaminophen-induced acute liver failure.
Methods: Mice were overdosed with acetaminophen followed by treatment with the Panx1 channel inhibitor 10Panx1 after 1.5 hours. Sampling was performed 24 hours after acetaminophen administration. Evaluation of the effect of Panx1 channel inhibition was based on a number of clinically relevant read-outs, including assessment of alanine and aspartate aminotransferase serum levels as well as histopathological examination of liver tissue with quantification of cell death. Inflammation was studied by measurement of cytokine levels in liver and serum.
Results: All parameters measured indicate a significant reduction of liver damage, including cell death and inflammation, upon treatment of acetaminophen-intoxicated mice with 10Panx1.
Conclusions: The results of this study demonstrate the clinical potential of Panx1 channel inhibition as a therapeutic strategy in the treatment of acetaminophen-induced acute liver failure.
Original language | English |
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Article number | S329 |
Number of pages | 1 |
Journal | Journal of Hepatology |
Volume | 62 |
Issue number | SI |
DOIs | |
Publication status | Published - 1 Apr 2015 |
Event | 50th International Liver Congress, 50th annual meeting of the European Association for the Study of the Liver - Vienna - Austria Duration: 22 Apr 2015 → 26 Apr 2015 http://https://ilc-congress.eu/ |
Keywords
- pannexin
- acetaminophen
- drug-induced liver injury
- hepatotoxicity
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OZR2651: International Joint Research Group - Liver Connexin and Pannexin Research Group (LCPR)
Vinken, M., Rogiers, V., Cogliati, B. & Dagli, M. L.
1/08/14 → 1/07/26
Project: Fundamental
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OZR2813: Bilaterale samenwerking ikv gemeenschappelijke doctoraatsproject: Bench Fee voor Joint PhD VUB-Universidade de Sao Paulo, Michael Maes
10/06/15 → 31/07/17
Project: Fundamental
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EU457: CONNECT: Connexin and pannexin channels as drug targets and biomarkers in acute and chronic liver disease
1/03/14 → 28/02/19
Project: Fundamental
Research output
- 1 Article
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Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity
Maes, M., McGill, M. R., da Silva, T. C., Abels, C., Lebofsky, M., Weemhoff, J. L., Tiburcio, T., Veloso Alves Pereira, I., Willebrords, J., Crespo Yanguas, S., Farhood, A., Beschin, A., Van Ginderachter, J. A., Penuela, S., Jaeschke, H., Cogliati, B. & Vinken, M., 1 May 2017, In: Archives of Toxicology. 91, 5, p. 2245-2261 17 p.Research output: Contribution to journal › Article › peer-review
17 Citations (Scopus)
Activities
- 1 Talk or presentation at a conference
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50th International Liver Congress, 50th annual meeting of the European Association for the Study of the Liver
Michaël Maes (Speaker)
22 Apr 2015 → 26 Apr 2015Activity: Talk or presentation › Talk or presentation at a conference