Skip to main content

Advertisement

SpringerLink
Log in

Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity

  • Organ Toxicity and Mechanisms
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

An Erratum to this article was published on 27 February 2017

Abstract

Pannexins constitute a relatively new family of transmembrane proteins that form channels linking the cytoplasmic compartment with the extracellular environment. The presence of pannexin1 in the liver has been documented previously, where it underlies inflammatory responses, such as those occurring upon ischemia–reperfusion injury. In the present study, we investigated whether pannexin1 plays a role in acute drug-induced liver toxicity. Hepatic expression of pannexin1 was characterized in a mouse model of acetaminophen-induced hepatotoxicity. Subsequently, mice were overdosed with acetaminophen followed by treatment with the pannexin1 channel inhibitor 10Panx1. Sampling was performed 1, 3, 6, 24 and 48 h after acetaminophen administration. Evaluation of the effects of pannexin1 channel inhibition was based on a number of clinically relevant readouts, including protein adduct formation, measurement of aminotransferase activity and histopathological examination of liver tissue as well as on a series of markers of inflammation, oxidative stress and regeneration. Although no significant differences were found in histopathological analysis, pannexin1 channel inhibition reduced serum levels of alanine and aspartate aminotransferase. This was paralleled by a reduced amount of neutrophils recruited to the liver. Furthermore, alterations in the oxidized status were noticed with upregulation of glutathione levels upon suppression of pannexin1 channel opening. Concomitant promotion of regenerative activity was detected as judged on increased proliferating cell nuclear antigen protein quantities in 10Panx1-treated mice. Pannexin1 channels are important actors in liver injury triggered by acetaminophen. Inhibition of pannexin1 channel opening could represent a novel approach for the treatment of drug-induced hepatotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

ALT:

Alanine aminotransferase

ANOVA:

Analysis of variance

APAP:

Acetaminophen

ASC:

Apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain

AST:

Aspartate aminotransferase

ATP:

Adenosine triphosphate

Casp1:

Caspase1

CD:

Cluster of differentiation

ELISA:

Enzyme-linked immunosorbent assay

Gly:

Glycosylated

GSH:

Glutathione

GSSG:

Glutathione disulfide

IFNγ:

Interferon γ

IL-1β/6/10/18:

Interleukin 1β/6/10/18

n :

Number of repeats

Nalp3:

NACHT, LRR, and pyrin domain-containing protein 3

NAPQI:

N-acetyl-p-benzoquinone imine

p :

Probability

Panx:

Pannexin

PCNA:

Proliferating cell nuclear antigen

RT-qPCR:

Reverse transcription quantitative real-time polymerase chain reaction

SEM:

Standard error of the mean

TBS/T:

Tris-buffered saline solution containing 0.1% Tween-20

TNFα:

Tumor necrosis factor α

References

  • Antoine DJ et al (2009) High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo. Toxicol Sci 112:521–531

    Article  CAS  PubMed  Google Scholar 

  • Bajt ML, Lawson JA, Vonderfecht SL, Gujral JS, Jaeschke H (2000) Protection against Fas receptor-mediated apoptosis in hepatocytes and nonparenchymal cells by a caspase-8 inhibitor in vivo: evidence for a postmitochondrial processing of caspase-8. Toxicol Sci 58:109–117

    Article  CAS  PubMed  Google Scholar 

  • Bajt ML, Knight TR, Farhood A, Jaeschke H (2003) Scavenging peroxynitrite with glutathione promotes regeneration and enhances survival during acetaminophen-induced liver injury in mice. J Pharmacol Exp Ther 307:67–73

    Article  CAS  PubMed  Google Scholar 

  • Bao L, Locovei S, Dahl G (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett 572:65–68

    Article  CAS  PubMed  Google Scholar 

  • Bao Y, Chen Y, Ledderose C, Li L, Junger WG (2013) Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils. J Biol Chem 288:22650–22657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blazka ME, Wilmer JL, Holladay SD, Wilson RE, Luster MI (1995) Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 133:43–52

    Article  CAS  PubMed  Google Scholar 

  • Boassa D, Ambrosi C, Qiu F, Dahl G, Gaietta G, Sosinsky G (2007) Pannexin1 channels contain a glycosylation site that targets the hexamer to the plasma membrane. J Biol Chem 282:31733–31743

    Article  CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Brough D, Pelegrin P, Rothwell NJ (2009) Pannexin-1-dependent caspase-1 activation and secretion of IL-1beta is regulated by zinc. Eur J Immunol 39:352–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruzzone R, Hormuzdi SG, Barbe MT, Herb A, Monyer H (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci USA 100:13644–13649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Celetti SJ, Cowan KN, Penuela S, Shao Q, Churko J, Laird DW (2010) Implications of pannexin 1 and pannexin 3 for keratinocyte differentiation. J Cell Sci 123:1363–1372

    Article  CAS  PubMed  Google Scholar 

  • Chekeni FB et al (2010) Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 467:863–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cisneros-Mejorado A et al (2015) Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage. J Cereb Blood Flow Metab 35:843–850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Connolly MK et al (2011) Dendritic cell depletion exacerbates acetaminophen hepatotoxicity. Hepatology 54:959–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cover C, Liu J, Farhood A, Malle E, Waalkes MP, Bajt ML, Jaeschke H (2006) Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 216:98–107

    Article  CAS  PubMed  Google Scholar 

  • Csak T, Ganz M, Pespisa J, Kodys K, Dolganiuc A, Szabo G (2011) Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology 54:133–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dahlin DC, Miwa GT, Lu AY, Nelson SD (1984) N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci USA 81:1327–1331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elliott MR et al (2009) Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 461:282–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganz M, Csak T, Nath B, Szabo G (2011) Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver. World J Gastroenterol 17:4772–4778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci 67:322–328

    Article  CAS  PubMed  Google Scholar 

  • Gulbransen BD et al (2012) Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med 18:600–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ichai P, Samuel D (2011) Epidemiology of liver failure. Clin Res Hepatol Gastroenterol 35:610–617

    Article  PubMed  Google Scholar 

  • Imaeda AB et al (2009) Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 119:305–314

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ishida Y, Kondo T, Ohshima T, Fujiwara H, Iwakura Y, Mukaida N (2002) A pivotal involvement of IFN-gamma in the pathogenesis of acetaminophen-induced acute liver injury. FASEB J 16:1227–1236

    Article  CAS  PubMed  Google Scholar 

  • Ishida Y, Kondo T, Kimura A, Tsuneyama K, Takayasu T, Mukaida N (2006) Opposite roles of neutrophils and macrophages in the pathogenesis of acetaminophen-induced acute liver injury. Eur J Immunol 36:1028–1038

    Article  CAS  PubMed  Google Scholar 

  • Iwamoto T, Nakamura T, Doyle A, Ishikawa M, de Vega S, Fukumoto S, Yamada Y (2010) Pannexin 3 regulates intracellular ATP/cAMP levels and promotes chondrocyte differentiation. J Biol Chem 285:18948–18958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaeschke H (1990) Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. J Pharmacol Exp Ther 255:935–941

    CAS  PubMed  Google Scholar 

  • Jaeschke H, Mitchell JR (1990) Use of isolated perfused organs in hypoxia and ischemia/reperfusion oxidant stress. Methods Enzymol 186:752–759

    Article  CAS  PubMed  Google Scholar 

  • Jaeschke H, Williams CD, Ramachandran A, Bajt ML (2012) Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int 32:8–20

    Article  CAS  PubMed  Google Scholar 

  • James LP, Kurten RC, Lamps LW, McCullough S, Hinson JA (2005) Tumour necrosis factor receptor 1 and hepatocyte regeneration in acetaminophen toxicity: a kinetic study of proliferating cell nuclear antigen and cytokine expression. Basic Clin Pharmacol Toxicol 97:8–14

    Article  CAS  PubMed  Google Scholar 

  • Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB (1973) Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. J Pharmacol Exp Ther 187:195–202

    CAS  PubMed  Google Scholar 

  • Kim HY, Kim SJ, Lee SM (2015) Activation of NLRP3 and AIM2 inflammasomes in Kupffer cells in hepatic ischemia/reperfusion. FEBS J 282:259–270

    Article  CAS  PubMed  Google Scholar 

  • Knight TR, Kurtz A, Bajt ML, Hinson JA, Jaeschke H (2001) Vascular and hepatocellular peroxynitrite formation during acetaminophen toxicity: role of mitochondrial oxidant stress. Toxicol Sci 62:212–220

    Article  CAS  PubMed  Google Scholar 

  • Lawson JA, Farhood A, Hopper RD, Bajt ML, Jaeschke H (2000) The hepatic inflammatory response after acetaminophen overdose: role of neutrophils. Toxicol Sci 54:509–516

    Article  CAS  PubMed  Google Scholar 

  • Le Vasseur M, Lelowski J, Bechberger JF, Sin WC, Naus CC (2014) Pannexin 2 protein expression is not restricted to the CNS. Front Cell Neurosci 8:392

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee WM (2008) Etiologies of acute liver failure. Semin Liver Dis 28:142–152

    Article  PubMed  Google Scholar 

  • Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ (1996) Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 271:12063–12067

    Article  CAS  PubMed  Google Scholar 

  • Liu ZX, Han D, Gunawan B, Kaplowitz N (2006) Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology 43:1220–1230

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Maes M et al (2016a) Involvement of connexin43 in acetaminophen-induced liver injury. Biochim Biophys Acta 1862:1111–1121

    Article  CAS  PubMed  Google Scholar 

  • Maes M et al (2016b) Connexin32: a mediator of acetaminophen-induced liver injury? Toxicol Mech Methods 26:88–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maes M, Vinken M, Jaeschke H (2016c) Experimental models of hepatotoxicity related to acute liver failure. Toxicol Appl Pharmacol 290:86–97

    Article  CAS  PubMed  Google Scholar 

  • Marina-García N, Franchi L, Kim YG, Miller D, McDonald C, Boons GJ, Núñez G (2008) Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2. J Immunol 180:4050–4057

    Article  PubMed  Google Scholar 

  • Marques PE et al (2012) Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology 56:1971–1982

    Article  CAS  PubMed  Google Scholar 

  • Martin-Murphy BV, Holt MP, Ju C (2010) The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice. Toxicol Lett 192:387–394

    Article  CAS  PubMed  Google Scholar 

  • Martinon F, Burns K, Tschopp J (2002) The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 10:417–426

    Article  CAS  PubMed  Google Scholar 

  • McGill MR et al (2013) Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: dose-response, mechanisms, and clinical implications. Toxicol Appl Pharmacol 269:240–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehendale HM (2005) Tissue repair: an important determinant of final outcome of toxicant-induced injury. Toxicol Pathol 33:41–51

    Article  CAS  PubMed  Google Scholar 

  • Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, Brodie BB (1973) Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther 187:185–194

    CAS  PubMed  Google Scholar 

  • Muldrew KL, James LP, Coop L, McCullough SS, Hendrickson HP, Hinson JA, Mayeux PR (2002) Determination of acetaminophen-protein adducts in mouse liver and serum and human serum after hepatotoxic doses of acetaminophen using high-performance liquid chromatography with electrochemical detection. Drug Metabol Dispos 30:446–451

    Article  CAS  Google Scholar 

  • Mylvaganam S et al (2010) Hippocampal seizures alter the expression of the pannexin and connexin transcriptome. J Neurochem 112:92–102

    Article  CAS  PubMed  Google Scholar 

  • Orellana JA et al (2011a) ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J Neurochem 118:826–840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orellana JA et al (2011b) Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J Neurosci 31:4962–4977

    Article  CAS  PubMed  Google Scholar 

  • Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S (2000) A ubiquitous family of putative gap junction molecules. Curr Biol 10:473–474

    Article  Google Scholar 

  • Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pelegrin P, Barroso-Gutierrez C, Surprenant A (2008) P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage. J Immunol 180:7147–7157

    Article  CAS  PubMed  Google Scholar 

  • Penuela S et al (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120:3772–3783

    Article  CAS  PubMed  Google Scholar 

  • Penuela S, Bhalla R, Nag K, Laird DW (2009) Glycosylation regulates pannexin intermixing and cellular localization. Mol Biol Cell 20:4313–4323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penuela S, Gehi R, Laird DW (2013) The biochemistry and function of pannexin channels. Biochim Biophys Acta 1828:15–22

    Article  CAS  PubMed  Google Scholar 

  • Qu Y et al (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186:6553–6561

    Article  CAS  PubMed  Google Scholar 

  • Sáez PJ, Shoji KF, Aguirre A, Sáez JC (2014) Regulation of hemichannels and gap junction channels by cytokines in antigen-presenting cells. Mediat Inflamm 2014:742734

    Article  Google Scholar 

  • Sandilos JK, Chiu YH, Chekeni FB, Armstrong AJ, Walk SF, Ravichandran KS, Bayliss DA (2012) Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region. J Biol Chem 287:11303–11311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silverman WR et al (2009) The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J Biol Chem 284:18143–18151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swayne LA, Sorbara CD, Bennett SA (2010) Pannexin 2 is expressed by postnatal hippocampal neural progenitors and modulates neuronal commitment. J Biol Chem 285:24977–24986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson RJ et al (2008) Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science 322:1555–1559

    Article  CAS  PubMed  Google Scholar 

  • Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang N et al (2013) Paracrine signaling through plasma membrane hemichannels. Biochim Biophys Acta 1828:35–50

    Article  CAS  PubMed  Google Scholar 

  • Williams CD, Bajt ML, Farhood A, Jaeschke H (2010a) Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice. Liver Int 30:1280–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams CD, Farhood A, Jaeschke H (2010b) Role of caspase-1 and interleukin-1beta in acetaminophen-induced hepatic inflammation and liver injury. Toxicol Appl Pharmacol 247:169–178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams CD et al (2011) Role of the Nalp3 inflammasome in acetaminophen-induced sterile inflammation and liver injury. Toxicol Appl Pharmacol 252:289–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams CD, Bajt ML, Sharpe MR, McGill MR, Farhood A, Jaeschke H (2014) Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans. Toxicol Appl Pharmacol 275:122–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao F, Waldrop SL, Khimji AK, Kilic G (2012) Pannexin1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated free fatty acids in liver cells. Am J Physiol Cell Physiol 303:1034–1044

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the grants of the Agency for Innovation by Science and Technology in Flanders (IWT Grant 131003), the European Research Council (ERC Starting Grant 335476), the Fund for Scientific Research-Flanders (FWO Grants G009514N and G010214N), the University Hospital of the Vrije Universiteit Brussel-Belgium (“Willy Gepts Fonds” UZ-VUB), the University of São Paulo-Brazil, the Foundation for Research Support of the State of São Paulo (FAPESP SPEC grant 2013/50420-6) and the National Institutes of Health (NIH Grants DK102142 and P20 GM103549). The authors wish to thank Miss Tineke Vanhalewyn, Miss Dinja De Win, Miss Shirlei Meire da Silva, Miss Cintia Maria Monteiro de Araújo, Dr. André G. Oliveira, Dr. Pedro E. Marques, Dr. Gustavo B. Menezes, Mister José Alexandre Coelho Pimental and Mister Paul Claes for their dedicated technical assistance.

Author information

Author notes

  1. Mitchell R. McGill

    Present address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA

Authors and Affiliations

  1. Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium

    Michaël Maes, Joost Willebrords, Sara Crespo Yanguas & Mathieu Vinken

  2. Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

    Mitchell R. McGill, Margitta Lebofsky, James L. Weemhoff & Hartmut Jaeschke

  3. Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

    Tereza Cristina da Silva, Taynã Tiburcio, Isabel Veloso Alves Pereira & Bruno Cogliati

  4. Myeloid Cell Immunology Lab, VIB Inflammation Research Center, Ghent, Belgium

    Chloé Abels, Alain Beschin & Jo A. Van Ginderachter

  5. Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium

    Chloé Abels, Alain Beschin & Jo A. Van Ginderachter

  6. Department of Pathology, St. David’s North Austin Medical Center, Austin, TX, USA

    Anwar Farhood

  7. Department of Anatomy and Cell Biology, University of Western Ontario, London, Canada

    Silvia Penuela

Authors
  1. Michaël Maes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitchell R. McGill
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tereza Cristina da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chloé Abels
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margitta Lebofsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. James L. Weemhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Taynã Tiburcio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Isabel Veloso Alves Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joost Willebrords
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sara Crespo Yanguas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anwar Farhood
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alain Beschin
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jo A. Van Ginderachter
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Silvia Penuela
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hartmut Jaeschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Bruno Cogliati
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mathieu Vinken
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mathieu Vinken.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

Additional information

Bruno Cogliati and Mathieu Vinken share equal seniorship.

An erratum to this article is available at http://dx.doi.org/10.1007/s00204-016-1929-y.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 532 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maes, M., McGill, M.R., da Silva, T.C. et al. Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity. Arch Toxicol 91, 2245–2261 (2017). https://doi.org/10.1007/s00204-016-1885-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-016-1885-6

Keywords

Search

Navigation