tretinoin and ferrous-sulfate

Alzheimer's disease (AD) a progressive neurodegenerative disorder of later life, is characterized by brain deposition of amyloid beta-protein (Abeta) plaques, accumulation of intracellular neurofibrillatory tangles, synaptic loss and neuronal cell death. There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. In the present study Abeta formation was induced in NT2N neurons, one of the most appropriate cell line models in AD. Our results indicate that oxidative stress resulting from the treatment of H(2)O(2)/FeSO(4) and/or 4-hydroxy-2-noenal (HNE) can be inhibited in the presence of tBHQ, a known inducer of nuclear factor-erythroid 2 related factor 2 (Nrf2) in NT2N neurons and can therefore be used to elucidate the relationship between oxidative stress, Abeta formation and Nrf2. The role of Nrf2 was confirmed using retinoic acid as an inhibitor of Nrf2. It provides the first documentation that tBHQ not only protects the neurons against cell death but also decreases amyloid beta formation. Moreover, the results indicate that oxidative stress fosters Abeta formation in NT2N neurons, creating a vicious neurodegenerative loop.

Topics: Aldehydes; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antineoplastic Agents; Antioxidants; Astrocytes; Caspase 3; Cell Line; Cysteine Proteinase Inhibitors; Enzyme Activation; Ferrous Compounds; Glutathione; Humans; Hydrogen Peroxide; Hydroquinones; Neurons; NF-E2-Related Factor 2; Oxidants; Oxidative Stress; Tretinoin

Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene.

Topics: Animals; Ascorbic Acid; Brain; Diterpenes; Ferrous Compounds; Free Radicals; Lipid Peroxidation; Male; Malondialdehyde; Mitochondria; Rats; Rats, Inbred Strains; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A