3-nitrotyrosine and ferulic-acid

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.

Topics: Animals; Blood Urea Nitrogen; Cisplatin; Coumaric Acids; Curcumin; Heme Oxygenase (Decyclizing); Kidney; Kidney Diseases; Male; Malondialdehyde; Peroxidase; Protective Agents; Rats, Wistar; RNA, Messenger; Tyrosine

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

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) provides neuroprotection against apoptosis in a transient middle cerebral artery occlusion (MCAo) model. This study was to further investigate the anti-apoptotic effect of FA during reperfusion after cerebral ischemia.. Rats were subjected to 90 min of cerebral ischemia followed by 3 or 24 h of reperfusion after which they were sacrificed.. Intravenous FA (100 mg/kg) administered immediately after middle cerebral artery occlusion (MCAo) or 2 h after reperfusion effectively abrogated the elevation of postsynaptic density-95 (PSD-95), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), nitrotyrosine, and cleaved caspase-3 levels as well as apoptosis in the ischemic cortex at 24 h of reperfusion. FA further inhibited Bax translocation, cytochrome c release, and p38 mitogen-activated protein (MAP) kinase phosphorylation. Moreover, FA enhanced the expression of gamma-aminobutyric acid type B receptor subunit 1 (GABA(B1)) in the ischemic cortex at 3 and 24 h of reperfusion. In addition, nitrotyrosine-positive cells colocalized with cleaved caspase-3-positive cells, and phospho-p38 MAP kinase-positive cells colocalized with nitrotyrosine- and Bax-positive cells, indicating a positive relationship among the expression of nitrotyrosine, phospho-p38 MAP kinase, Bax, and cleaved caspase-3. The mutually exclusive expression of GABA(B1) and nitrotyrosine revealed that there is a negative correlation between GABA(B1) and nitrotyrosine expression profiles. Additionally, pretreatment with saclofen, a GABA(B) receptor antagonist, abolished the neuroprotection of FA against nitric oxide (NO)-induced apoptosis.. FA significantly enhances GABA(B1) receptor expression at early reperfusion and thereby provides neuroprotection against p38 MAP kinase-mediated NO-induced apoptosis at 24 h of reperfusion.

Topics: Animals; Apoptosis; Brain Ischemia; Coumaric Acids; Disease Models, Animal; Free Radical Scavengers; Gene Expression Regulation; Male; Neuroprotective Agents; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley; Receptors, GABA-B; Reperfusion Injury; Tyrosine

Accumulating evidence indicates that glial cells are actively involved in the pathogenesis of Alzheimer's disease. We recently reported protective effects of long-term administration of ferulic acid against learning and memory deficit induced by centrally administered beta-amyloid peptide (Abeta)1-42 in mice. In that report, we found that the Abeta1-42-induced increases in immunoreactivities of glial fibrillary acidic protein, the astrocyte marker, and interleukin(IL)-1beta in the hippocampus are also suppressed by pretreatment with ferulic acid. In the present study, we aimed to further characterize the effect of long-term administration of ferulic acid on the centrally administered Abeta1-42-induced activation of glial cells in mice. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%) for 4 weeks, and then Abeta1-42 (410 pmol) was administered via intracerebroventricular injection. Intracerebroventricularly injected Abeta1-42 induced an increase in immunoreactivities of endothelial nitric oxide synthase (eNOS) and 3-nitrotyrosine (3-NT) in the activated astrocytes in the hippocampus. Pretreatment of ferulic acid for 4 weeks prevented the Abeta1-42-induced increase in eNOS and 3-NT immunoreactivities. Administration of ferulic acid per se induced a transient and slight increase in eNOS immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. Intracerebroventricularly injected Abeta1-42 also increased interleukin-1alpha(IL-1alpha) immunoreactivity in the hippocampus, which was also suppressed by pretreatment with ferulic acid. These results demonstrate that long-term administration of ferulic acid induces suppression of the centrallly injected Abeta1-42-induced activation of astrocytes which is suggested to underlie the protective effect of ferulic acid against Abeta1-42 toxicity in vivo.

Topics: Amyloid beta-Peptides; Animals; Astrocytes; Cell Count; Coumaric Acids; Drug Interactions; Free Radical Scavengers; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Immunohistochemistry; Injections, Intraventricular; Interleukin-1; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Peptide Fragments; Time Factors; Tyrosine

Peroxynitrite is a cytotoxic species generated by the reaction between superoxide and nitric oxide. In this study the ability of hydroxycinnamate antioxidants to decrease peroxynitrite-mediated nitration of tyrosine was investigated. The results obtained show that all compounds were able to inhibit nitration of tyrosine. The potency of inhibitory activity was in the order; caffeic acid > or = chlorogenic acid > or = ferulic acid > p-coumaric acid > ocoumaric acid > m-coumaric acid. Trolox, which was included in the study for comparative purposes, had an activity between that of ferulic acid and p-coumaric acid. The data obtained suggest that hydroxycinnamates can act by one of two possible mechanisms: preferential nitration for monophenolates and electron donation by catecholates.

Topics: Antioxidants; Caffeic Acids; Chlorogenic Acid; Chromans; Chromatography, High Pressure Liquid; Coumaric Acids; Free Radical Scavengers; Free Radicals; Nitrates; Spectrophotometry; Tyrosine