4-hydroxy-2-nonenal and ferulic-acid

Cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and a potential nutritional supplement for preventing retinal degeneration. However, the protective mechanism of C3G and its metabolites, protocatechuic acid (PCA) and ferulic acid (FA), remain unclear. The molecular mechanisms of C3G and its metabolites against retinal photooxidative damage in vivo are investigated.. Pigmented rabbits were orally administered C3G, PCA, and FA (0.11 mmol/kg/day) for 3 weeks. Electroretinography, histological analysis, and TUNEL assay showed that C3G and its metabolites attenuated retinal cell apoptosis. The expression of oxidative stress markers were upregulated after light exposure but attenuated by C3G and FA, which may be attributed to the elevated secretion and expression of heme oxygenase (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2). C3G, PCA, and FA attenuated the secretion or expression of inflammation-related genes; FA suppressed nuclear factor kappa B (NF-κB) activation. The treatments attenuated the light-induced changes on certain apoptotic proteins and angiogenesis-related cytokines.. C3G and FA reduced light-induced retinal oxidative stress by activating the Nrf2/HO-1 antioxidant pathway. FA attenuated the light-induced retinal inflammation by suppressing NF-κB activation. C3G and its metabolites attenuated the photooxidation-induced apoptosis and angiogenesis in the retina.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Anthocyanins; Antioxidants; Apoptosis; Coumaric Acids; Cytokines; Deoxyguanosine; Glucosides; Heme Oxygenase-1; Hydroxybenzoates; In Situ Nick-End Labeling; Light; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rabbits; Retina; Retinal Degeneration; Signal Transduction; Tyrosine; Up-Regulation

Our results are in agreement with the general idea that natural antioxidants achieve their best cytoprotective capacity if given before and soon after the stressor.. We focused on ferulic acid (FA, 4-hydroxy 3-methoxycinnamic acid), a phenolic compound that is known to exhibit antioxidant properties. Our study was designed to evaluate the effectiveness of FA for different schedules of treatment to establish the 'therapeutic window' for FA protection.. Guinea pigs were exposed to acoustic trauma (6 kHz at 120 dB for 60 min) and received a total dose of 600 mg/kg of FA. Group I, noise control; group II, noise + FA (150 mg/kg) for 4 days starting 24 h post exposure; group III, noise + FA (60 mg/kg) 1 h before and 9 days post exposure; group IV, noise + FA (60 mg/kg) given 3 days before and 7 days post exposure; group V, noise + FA (150 mg/kg) 1 h before and 3 days post noise exposure. Auditory brainstem response (ABR) test and immunohistochemical and morphological studies were performed.. Group V had significantly decreased noise-induced hearing loss at day 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress marker. The other schedules of drug administration showed a minor degree of protection.

Topics: Aldehydes; Animals; Cell Count; Coumaric Acids; Drug Administration Schedule; Evoked Potentials, Auditory, Brain Stem; Free Radical Scavengers; Guinea Pigs; Hair Cells, Auditory, Outer; Hearing Loss, Noise-Induced; Immunohistochemistry

Our previous studies have shown that ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) inhibits intercellular adhesion molecule-1 (ICAM-1) expression in the ischemic striatum after 2 h of reperfusion in a transient middle cerebral artery occlusion model in rats. The purpose of this study is to further investigate the neuroprotective effects of FA during reperfusion after cerebral ischemia. Rats were subjected to 90 min of ischemia; they were then sacrificed after 2, 10, 24 and 36 h of reperfusion. ICAM-1 and macrophage-1 antigen (Mac-1) mRNA were detected using semi-quantitative RT-PCR at 2 h of reperfusion. Mac-1, 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), active caspase 3, neuronal nuclei (NeuN) and TUNEL positive cells were measured at 2, 10, 24 and 36 h of reperfusion. FA (100 mg/kg, i.v.) administered immediately after MCAo inhibited ICAM-1 and Mac-1 mRNA expression in the striatum at 2 h of reperfusion, and reduced the number of Mac-1, 4-HNE and 8-OHdG positive cells in the ischemic rim and core at 10, 24 and 36 h of reperfusion. FA decreased TUNEL positive cells in the penumbra at 10 h, and in the ischemic boundary and core at 24 and 36 h of reperfusion. FA curtailed active caspase 3 expression in the penumbra at 10 h and restored NeuN-labeled neurons in the penumbra and ischemic core at 36 h of reperfusion. FA decreased the level of ICAM-1 mRNA and the number of microglia/macrophages, and subsequently down-regulated inflammation-induced oxidative stress and oxidative stress-related apoptosis, suggesting that FA provides neuroprotection against oxidative stress-related apoptosis by inhibiting ICAM-1 mRNA expression after cerebral ischemia/reperfusion injury in rats.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Apoptosis; Brain Ischemia; Caspase 3; Coumaric Acids; Deoxyguanosine; Disease Models, Animal; DNA-Binding Proteins; Encephalitis; Free Radical Scavengers; Gene Expression; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Intercellular Adhesion Molecule-1; Macrophage-1 Antigen; Male; Nerve Tissue Proteins; Neuroprotective Agents; Nuclear Proteins; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger