Abstract: Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis.
Abstract: Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO) action of SM. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B12, etc.), might have similar hepatoprotective effects as described in human nutrition.
Abstract: The study aimed at analyzing the metabolite profile of Nardostachys jatamansi using RP-HPLC, GC-MS and also its antioxidant, biomolecule protective and cytoprotective properties. The 70% ethanolic extract of Nardostachys jatamansi (NJE) showed the presence of polyphenols and flavonoids (gallic acid, catechin, chlorogenic acid, homovanillin, epicatechin, rutin hydrate and quercetin-3-rhamnoside) analyzed by RP-HPLC, whereas hexane extract revealed an array of metabolites (fatty acids, sesquiterpenes, alkane hydrocarbons and esters) by GC-MS analysis. The antioxidant assays showed the enhanced potency of NJE with a half maximal inhibitory concentration (IC50) value of 222.22 ± 7.4 μg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 13.90 ± 0.5 μg/mL for 2,2′-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 113.81 ± 4.2 μg/mL for superoxide, 948 ± 21.1 μg/mL for metal chelating and 12.3 ± 0.43 mg FeSO4 equivalent/g of extract for ferric reducing antioxidant power assays and was more potent than hexane extract. NJE effectively inhibited 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidation of biomolecules analyzed by pBR322 plasmid DNA damage, protein oxidation of bovine serum albumin and lipid peroxidation assays. The observed effects might be due to the high content of polyphenols, 53.06 ± 2.2 mg gallic acid equivalents/g, and flavonoids, 25.303 ± 0.9 mg catechin equivalents/g, of NJE compared to the hexane fraction. Additionally, the extract abrogated the protein, carbonyl, and ROS formation, and NJE showed cytotoxicity in SH-SY5Y neuronal cells above 75 μg/mL. Thus, the study suggests that the herb unequivocally is a potential source of antioxidants and could aid in alleviating oxidative stress-mediated disorders.
Abstract: In this study, the antioxidant activity of the Convolvulus arvensis Linn (CA) ethanol extract has been evaluated by different ways. The antioxidant activity of the extract assessed by 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical cation, the oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP) was 1.62 mmol Trolox equivalents (TE)/g DW, 1.71 mmol TE/g DW and 2.11 mmol TE/g DW, respectively. CA ethanol extract exhibited scavenging activity against the methoxy radical initiated by the Fenton reaction and measured by Electron Paramagnetic Resonance (EPR). The antioxidant effects of lyophilised CA measured in beef patties containing 0.1% and 0.3% (w/w) CA stored in modified atmosphere packaging (MAP) (80% O2 and 20% CO2) was determined. A preliminary study of gelatine based film containing CA showed a strong antioxidant effect in preventing the degradation of lipid in muscle food. Thus, the present results indicate that CA extract can be used as a natural food antioxidant.
Abstract: Objective: Normal iron handling appears to be disrupted in critically ill patients leading to hypoferremia that may contribute to systemic inflammation. Ceruloplasmin (Cp), an acute phase reactant protein that can convert ferrous iron to its less reactive ferric form facilitating binding to ferritin, has ferroxidase activity that is important to iron handling. Genetic absence of Cp decreases iron export resulting in iron accumulation in many organs. The objective of this study was to characterize iron metabolism and Cp activity in burn and non-burn trauma patients to determine if changes in Cp activity are a potential contributor to the observed hypoferremia. Material and Methods: Under Brooke Army Medical Center Institutional Review Board approved protocols, serum or plasma was collected from burn and non-burn trauma patients on admission to the ICU and at times up to 14 days and measured for indices of iron status, Cp protein and oxidase activity and cytokines. Results: Burn patients showed evidence of anemia and normal or elevated ferritin levels. Plasma Cp oxidase activity in burn and trauma patients were markedly lower than controls on admission and increased to control levels by day 3, particularly in burn patients. Plasma cytokines were elevated throughout the 14 days study along with evidence of an oxidative stress. No significant differences in soluble transferrin receptor were noted among groups on admission, but levels in burn patients were lower than controls for the first 5 days after injury. Conclusion: This study further established the hypoferremia and inflammation associated with burns and trauma. To our knowledge, this is the first study to show an early decrease in Cp oxidase activity in burn and non-burn trauma patients. The results support the hypothesis that transient loss of Cp activity contributes to hypoferremia and inflammation. Further studies are warranted to determine if decreased Cp activity increases the risk of iron-induced injury following therapeutic interventions such as transfusions with blood that has undergone prolonged storage in trauma resuscitation.
Antioxidants2015, 4(1), 134-152; doi:10.3390/antiox4010134 - published 27 February 2015 Show/Hide Abstract
Abstract: The biological effects of high-dose total body ionizing irradiation [(thereafter, irradiation (IR)] are attributed to primary oxidative breakage of biomolecule targets, mitotic, apoptotic and necrotic cell death in the dose-limiting tissues, clastogenic and epigenetic effects, and cascades of functional and reactive responses leading to radiation sickness defined as the acute radiation syndrome (ARS). The range of remaining and protracted injuries at any given radiation dose as well as the dynamics of post-IR alterations is tissue-specific. Therefore, functional integrity of the homeostatic tissue barriers may decline gradually within weeks in the post-IR period culminating with sepsis and failure of organs and systems. Multiple organ failure (MOF) leading to moribundity is a common sequela of the hemotapoietic form of ARS (hARS). Onset of MOF in hARS can be presented as “two-hit phenomenon” where the “first hit” is the underlying consequences of the IR-induced radiolysis in cells and biofluids, non-septic inflammation, metabolic up-regulation of pro-oxidative metabolic reactions, suppression of the radiosensitive hematopoietic and lymphoid tissues and the damage to gut mucosa and vascular endothelium. While the “second hit” derives from bacterial translocation and spread of the bacterial pathogens and inflammagens through the vascular system leading to septic inflammatory, metabolic responses and a cascade of redox pro-oxidative and adaptive reactions. This sequence of events can create a ground for development of prolonged metabolic, inflammatory, oxidative, nitrative, and carbonyl, electrophilic stress in crucial tissues and thus exacerbate the hARS outcomes. With this perspective, the redox mechanisms, which can mediate the IR-induced protracted oxidative post-translational modification of proteins, oxidation of lipids and carbohydrates and their countermeasures in hARS are subjects of the current review. Potential role of ubiquitous, radioresistant mesenchymal stromal cells in the protracted responses to IR and IR-related septicemia is also discussed.