curcumin and Deficiency-Diseases

While oxidative stress is a feature of non-alcoholic steatohepatitis, the causal link between oxidative stress and inflammatory recruitment has yet to be demonstrated. We analysed the role of NF-kappaB redox-sensitive signalling pathway of inflammatory recruitment in experimental steatohepatitis.. Mice were fed the methionine and choline deficient (MCD) or the control diet, with or without curcumin, an NF-kappaB inhibitor, for up to 4 weeks. Histopathology, lipoperoxides, NF-kappaB/DNA binding and expression of NF-kappaB-regulated genes were assessed.. MCD-fed mice developed steatohepatitis accompanied by dramatic accumulation of hepatic lipoperoxides, activation of NF-kappaB and induction of pro-inflammatory ICAM-1, COX-2, MCP-1 and CINC mRNA. Curcumin significantly reduced MCD-induced inflammation but had no effect on steatosis or on the level of hepatic lipid peroxides. Curcumin prevented the MCD-induced activation of NF-kappaB and decreased downstream induction of ICAM-1, COX-2 and MCP-1. However, it failed to reduce activation of AP-1, MAPK pathways or CINC expression.. Curcumin alleviates the severity of hepatic inflammation in experimental steatohepatitis induced by the MCD diet, an effect likely to be mediated via inhibition of NF-kB activation and dependent pro-inflammatory genes. The NF-kappaB pathway is one among several possible signalling pathways by which inflammation is recruited in experimental steatohepatitis.

Topics: Animals; Chemokine CCL2; Choline Deficiency; Collagen Type I; Curcumin; Cyclooxygenase 2; Deficiency Diseases; Diet; Enzyme Inhibitors; Fatty Liver; Female; Hepatitis; Inflammation Mediators; Intercellular Adhesion Molecule-1; Methionine; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Severity of Illness Index; Transcription Factor AP-1