curcumin and ferrous-sulfate

Micro RNAs (miRNAs) constitute a unique class of small, non-coding ribonucleic acids (RNAs) that regulate gene expression at the post-transcriptional level. The presence of two inducible miRNAs, miRNA-125b and miRNA-146a, involved in respectively, astroglial cell proliferation and in the innate immune and inflammatory response, is significantly up-regulated in human neurological disorders including Alzheimer's disease (AD). In this study we analyzed abundances miRNA-125b and miRNA-146a in magnesium-, iron-, gallium, and aluminum-sulfate-stressed human-astroglial (HAG) cells, a structural and immune-responsive brain cell type. The combination of iron- plus aluminum-sulfate was found to be significantly synergistic in up-regulating reactive oxygen species (ROS) abundance, NF-кB-DNA binding and miRNA-125b and miRNA-146a expression. Treatment of metal-sulfate stressed HAG cells with the antioxidant phenyl butyl nitrone (PBN) or the NF-кB inhibitors curcumin, the metal chelator-anti-oxidant pyrollidine dithiocarbamate (PDTC), or the resveratrol analog CAY10512, abrogated both NF-кB signaling and induction of these miRNAs. Our observations further illustrate the potential of physiologically relevant amounts of aluminum and iron sulfates to synergistically up-regulate specific miRNAs known to contribute to AD-relevant pathogenetic mechanisms, and suggest that antioxidants or NF-кB inhibitors may be useful to quench metal-sulfate triggered genotoxicity.

Topics: Alum Compounds; Astrocytes; Cells, Cultured; Curcumin; Cyclic N-Oxides; Drug Synergism; Environmental Pollutants; Ferrous Compounds; Free Radical Scavengers; Gene Expression; Glial Fibrillary Acidic Protein; Humans; MicroRNAs; NF-kappa B; Oxidative Stress; Primary Cell Culture; Reactive Oxygen Species; Up-Regulation

Male Wistar rats were fed a control diet or the control diet supplemented with 1% (by weight) turmeric for 10 wk. In rats injected with 30 mg Fe2+/kg body weight, lipid peroxidation was 29 and 35% lower in liver homogenates and microsomes, respectively, of turmeric-fed rats than in those of rats fed the control diet. The activities of superoxide dismutase, catalase and glutathione peroxidase were higher (by 19, 19 and 20%, respectively) in liver homogenates of rats fed the turmeric-containing diet in comparison with the controls. These studies indicate that dietary turmeric lowers lipid peroxidation by enhancing the activities of antioxidant enzymes.

Topics: Animals; Catalase; Curcuma; Curcumin; Diet; Ferrous Compounds; Glutathione Peroxidase; Lipid Peroxidation; Liver; Male; Microsomes, Liver; Plant Extracts; Rats; Rats, Wistar; Reactive Oxygen Species; Sesquiterpenes; Superoxide Dismutase