Title |
3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism
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Published in |
Digestive Diseases and Sciences, September 2018
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DOI | 10.1007/s10620-018-5267-1 |
Pubmed ID | |
Authors |
Joram Wardi, Orna Ernst, Anna Lilja, Hussein Aeed, Sebastián Katz, Idan Ben-Nachum, Iris Ben-Dror, Dolev Katz, Olga Bernadsky, Rajendar Kandhikonda, Yona Avni, Iain D. C. Fraser, Roy Weinstain, Alexander Biro, Tsaffrir Zor |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 10 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 3 | 30% |
Student > Doctoral Student | 2 | 20% |
Researcher | 1 | 10% |
Student > Bachelor | 1 | 10% |
Unknown | 3 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 30% |
Medicine and Dentistry | 2 | 20% |
Immunology and Microbiology | 1 | 10% |
Agricultural and Biological Sciences | 1 | 10% |
Unknown | 3 | 30% |