The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D-galactosamine in mice

Hepatobiliary & Pancreatic Diseases International : HBPD INT
Bing-Zhu YanBing-Rong Liu

Abstract

Acute liver failure (ALF) is a severe and life-threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releasing molecule (CORM-3) has been shown to have anti-inflammatory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activities (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-alpha, IL-6, IL-1beta and IL-10) and liver immunohistochemistry of NF-kappaB-p65 were determined; the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. The pretreatment with CORM-3 significantly improved the liver histology and the survival rate of mice compared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) and increased the anti-inflammatory cytokine (IL-10) productio...Continue Reading

Citations

Nov 14, 2018·Current Medicinal Chemistry·Kazuaki TaguchiMasaki Otagiri
Apr 29, 2021·Antioxidants & Redox Signaling·Libor Vítek
Jul 18, 2018·European Journal of Pharmacology·Paolo FagoneFerdinando Nicoletti

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