3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism


Background and Aims

Concanavalin A is known to activate T cells and to cause liver injury and hepatitis, mediated in part by secretion of TNFα from macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to prevent tissue damage in various animal models of inflammation. The objectives of this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3-aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage.


We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to act as a scavenger in in vitro assays.


3-AB markedly reduced inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFκB transcriptional activity and subsequent expression of TNFα and iNOS and blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor diphenyleneiodonium (DPI) also inhibited TNFα expression in stimulated macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFκB activity. PARP-1 knockout failed to affect NFκB and TNFα suppression by 3-AB in stimulated macrophages.


Our results suggest that 3-AB has a therapeutic effect on concanavalin A-induced liver injury by inhibiting expression of the key pro-inflammatory cytokine TNFα, via PARP-1-independent NFκB suppression and via an NFκB-independent anti-oxidative mechanism.

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Alanine aminotransferase


Aspartate aminotransferase


Concanavalin A




Horseradish peroxidase


Interferon γ




Malate dehydrogenase




Nuclear factor kappa B


Nitric oxide


NADPH oxidase


Poly(ADP-ribose) polymerase-1




Reactive oxygen species


Superoxide dismutase


Tumor necrosis factor α


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We are grateful to Dr. C. Daniels and M. Athamna for critical reading of the manuscript, to Dr. M. Cohen-Armon for various reagents and helpful discussions, to Dr. E. Pick and Dr. E. Bechor for the help with the superoxide assay and insightful discussions; to Dr. D. Shabat, N. Hananya and O. Green for help with fluorescence measurement; to Dr. C. Yu (Xiamen University, Xiamen, Fujian, China) for the TNFα promoter luciferase plasmid; to Dr. M. Montminy (Salk Institute, La-Jolla, CA) for the CRE-luciferase plasmid; to Dr. P. Angel (German Cancer Research Center, Heidelberg, Germany) for the AP-1-luciferase plasmid; to Dr. Ariel Munitz (TAU, Israel) for the iNOS antibody; and to Dr. Y. Ebenstein (TAU, Israel) for the EL-4 cell line.


This work was supported by the United States – Israel Binational Science Foundation [Grant 2011360 to TZ]. IF is supported by the Intramural Research Program of NIAID, NIH.

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JW, AB and TZ conceived and designed the study; OE, AL, HA, SK, IBN, IBD, DK, and KR performed the experiments; JW, OE, AL, HA, SK, DK, OB, KR, IF, RW, AB, and TZ analyzed the data; JW, OE, AB, and TZ wrote the manuscript.

Corresponding authors

Correspondence to Joram Wardi or Alexander Biro or Tsaffrir Zor.

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The authors declare that they have no conflict of interest.

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All animal experiments were performed in accordance with the guidelines of the Care and Use of Laboratory Animals and have been approved by the research ethics committee at Wolfson medical center.

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Wardi, J., Ernst, O., Lilja, A. et al. 3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism. Dig Dis Sci 63, 3382–3397 (2018). https://doi.org/10.1007/s10620-018-5267-1

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  • Liver failure
  • Inflammation
  • Macrophages
  • TNFα
  • Reactive oxygen species
  • NFκB