rutin and Neurodegenerative-Diseases

The oxidation of bioorganic materials by air and, particularly, the oxidative stress involved in the cell loss and other pathologies associated with neurodegenerative diseases (NDs) are of enormous social and economic importance. NDs generally involve free radical reactions, beginning with the formation of an initiating radical by some redox, thermal or photochemical process, causing nucleic acid, protein and lipid oxidations and the production of harmful oxidative products. Physically, persons afflicted by NDs suffer progressive loss of memory and thinking ability, mood swings, personality changes, and loss of independence. Therefore, the development of antioxidant strategies to retard or minimize the oxidative degradation of bioorganic materials has been, and still is, of paramount importance. While we are aware of the importance of investigating the biological and medical aspects of the diseases, elucidation of the associated chemistry is crucial to understanding their progression, heading to intelligent chemical intervention to find more efficient therapies to prevent or delay the onset of the diseases. Accordingly, this review aims to provide the reader with a chemical base to understand the behavior and properties of the reactive oxygen species involved and of typical radical scavengers such as polyphenolic antioxidants. Some discussion on the structures of the various species, their formation, chemical reactivities and lifetimes is included. The ultimate goal is to understand how, when and where they form, how far they travel prior to react, which molecules are their targets, and how we can, eventually, control their activity to minimize their impact by means of chemical methods. Recent strategies explore chemical modifications of the hydrophobicity of potent, natural antioxidants to improve their efficiency by fine-tuning their concentrations at the reaction site.

Topics: Animals; Free Radicals; Humans; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Stress; Polyphenols; Reactive Oxygen Species

Troxerutin, a natural flavonoid guards against oxidative stress and apoptosis with a high capability of passing through the blood-brain barrier. Our aim was to investigate the role of troxerutin in experimentally induced retinal neurodegeneration by modulating the interferon-gamma (IFNγ)-extracellular signal-regulated kinases 1/2 (ERK1/2)-CCAAT enhancer-binding protein β (C/EBP-β) signaling pathway. Three groups of rats (10 each group) were included. Group I (control group), group II (rotenone treated group): the rats were injected subcutaneously with a single rotenone dosage of 3 mg/kg repeated every 48 hours for 60 days to trigger retinal neurodegeneration. Group III (troxerutin-treated group): rats received troxerutin (150 mg/kg/day) by oral gavage 1 hour before rotenone administration. A real-time polymerase chain reaction technique was applied to measure messenger RNA (mRNA) levels of retinal C/EBP-β. Enzyme-linked immunosorbent assay technique was utilized to assay tumor necrosis factor-α (TNF-α), IFNγ, and ERK1/2 levels. Finally, reactive oxygen species (ROS), as well as carbonylated protein (CP) levels, were assessed spectrophotometrically. Improved retinal neurodegeneration by downregulation of C/EBP-β mRNA gene expression, also caused a significant reduction of TNF-α, IFNγ, ERK1/2 as well as ROS and CP levels compared with the diseased group. These findings could hold promise for the usage of troxerutin as a protective agent against rotenone-induced retinal neurodegeneration.

Topics: Animals; CCAAT-Enhancer-Binding Protein-beta; Disease Models, Animal; Down-Regulation; Gene Expression; Hydroxyethylrutoside; Interferon-gamma; Male; MAP Kinase Signaling System; Neurodegenerative Diseases; Protective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Retinal Diseases; RNA, Messenger; Rotenone; Tumor Necrosis Factor-alpha