Role Of Free Radical Generation Research Articles

Study of Serum Zinc and Copper Levels and Tumor Pathology: A Pilot Study in People Affected with Head and Neck Cancers.

This study aimed to determine understanding the role of serum copper, zinc and copper/zinc ratio with tumor staging in people newly diagnosed to be affected with Head and Neck cancer and by comparing with age matched health individuals devoid of any orodental maladies. The study included patients confirmed to be affected with HN cancer with histological diagnosis of Head and Neck cancer (60) and age matched healthy volunteers (N = 23). The demographic details like age, domicile, menopausal status and pathological details (like tumor stage, number of lymph node involvement, tumor size) were collected from the patient's hospital data file. The serum levels of zinc and copper assayed as per standard procedures and the zinc/copper was calculated for the cancer patients and controls. The data were subjected to unpaired "t" test and ANOVA with Bonferroni's multiple comparisons. The association between zinc and copper levels with pathological details between the variables was ascertained using the Pearson correlation coefficient(r). A statistical value of p < 0.05 was considered to be significant in agreeance to the accepted norms. Results: This result of the study indicates that when compared to the healthy individuals, the serum levels of copper, and zinc, and copper/zinc ratio were high in patients with H&N cancer. Also when compared with controls, the levels of zinc decreased, while that of copper and copper/zinc ratio increased in people affected with H&N cancer (p = 0.017 to 0.0001) and with the stage of the tumor (p = 0.03 to 0.001). The results of the study suggest that levels of serum zinc were significantly lower and that of copper higher in H&N cancer patients than that in controls and also that it was dependent on the tumor stage. When analyzed cumulatively the results hint that zinc and copper, due to their role in free radical generation and prevention have an important role in cancer progression and possible prevention by judicious intervention.

Comparison of the toxicity of sintered and unsintered indium-tin oxide particles in murine macrophage and epidermal cells

Indium-tin oxide (ITO) is used to produce flat panel displays and several other technology products. Composed of 90% indium oxide (In2O3) and 10% tin oxide (SnO2) by weight, ITO is synthesized under conditions of high heat via a process known as sintering. Indium lung disease, a recently recognized occupational illness, is characterized by pulmonary alveolar proteinosis, fibrosis, and emphysema. Murine macrophage (RAW 264.7) and epidermal (JB6) cells stably transfected with AP-1 to study tumor promoting potential, were used to differentiate between the toxicological profiles of sintered ITO (SITO) and unsintered mixture (UITO). We hypothesized that sintering would play a key role in free radical generation and cytotoxicity. Exposure of cells to both UITO and SITO caused a time and dose dependent decrease of the viability of cells. Intracellular ROS generation was inversely related to the dose of both UITO and SITO, a direct reflection of the decreased number of viable RAW 264.7 and JB6/AP-1 cells observed at higher concentrations. Electron spin resonance showed significantly increased hydroxyl radical (OH) generation in cells exposed to UITO compared to SITO. This is different from LDH release, which showed that SITO caused significantly increased damage to the cell membrane compared to UITO. Lastly, the JB6/AP-1 cell line did not show activation of the AP-1 pathway. Our results highlight both the differences in the mechanisms of cytotoxicity and the consistent adverse effects associated with UITO and SITO exposure.

A study of oxidative stress in neonates delivered through meconium-stained amniotic fluid.

The present study suggest that the neonates born through MSAF experience higher degrees of oxidative stress, as evidenced by increased levels of cord blood plasma MDA and 8-OH-dG. What is known: • Aspirated meconium has been found to induce free radical generation and cellular damage in animal studies. • Its role in free radical generation and oxidative damage in human neonates is scarce. What is new: • Neonates born through meconium-stained amniotic fluid experience significant oxidative stress.

Alopurinol y su papel en el tratamiento de la sarcopenia

Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and uric acid and plays an important role in purine catabolism. The purine analogue, allopurinol, is a well-known inhibitor of XO widely used in the clinical management of gout and conditions associated with hyperuricemia. More recent data indicate that allopurinol reduces oxidative stress and improves vascular function in several cardiometabolic diseases, prolongs exercise time in angina, and improves the efficiency of cardiac contractility in heart failure. XO also plays an important role in free radical generation during skeletal muscle contraction and thus, it has been related to the muscle damage associated to exhaustive exercise. Several research groups have shown the protective effect of allopurinol in the prevention of this type of damage.Based on this background, a critical overview is presented on the possible role of allopurinol in the treatment of sarcopenia, a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes, such as physical disability, poor quality of life and death.

Proteomics-based identification of plasma proteins and their association with the host–pathogen interaction in chronic typhoid carriers

SummaryBackgroundCurrent diagnostic tests are inadequate to detect typhoid cases, as well as the chronic carrier state, the sole reservoir of Salmonella enterica serovar Typhi. The current study was conducted to find new molecular signatures of pathogen/disease to understand the mechanism behind the host–pathogen interaction in enteric fever.MethodsProteomics-based studies were done to determine the expression of differentially expressed proteins in the plasma of controls, acute typhoid cases, and chronic typhoid carriers. Further, transcriptome-based analysis using reverse-transcriptase PCR (RT-PCR) was done in controls, acute typhoid cases, and chronic typhoid carriers.ResultsResults showed the upregulation of proprotein convertase subtilisin, furin, haptoglobin, and albumin in the plasma of chronic typhoid carriers. The elevation in mRNA expression of four differentially expressed proteins confirms the changes at the transcriptional level. Further, the increase in albumin and haptoglobin in chronic typhoid carriers shows their role in free radical generation, inflammation, and monocyte cell signaling.ConclusionThrough proteomics techniques, this study identified four proteins in the chronic typhoid carrier host that may have a role in the disease pathogenesis of enteric fever.

Free Radicals in Diseases and Potential Role of Phytoconstituents-A Cause with Emerging Importance

Free radicals and oxidants play a dual role as both toxic and beneficial compounds, which in low/moderate concentrations are involved in normal physiological functions but excess production of free radicals or decrease in antioxidant level leads to oxidant stress. Free radicals are produced either from normal cell metabolisms in situ or from different external sources (pollution, cigarette smoke, radiation, medication etc). When an overload of free radicals cannot gradually be destroyed, their accumulation in the body is a harmful process that can mediate damage to cellular structures, including lipids, proteins, RNA and DNA leading to a number of diseases. ROS (reactive oxygen species) and RNS (reactive nitrogen species) in excess can damage biological processes, and this situation has been observed in various acute and chronic diseases such as cancer, autoimmune disorders, aging, cataract, cardiovascular and neurodegenerative diseases. This review deals in depth with the role of free radical generation, the mechanisms of formation and catabolism, and the role in various diseases and the function of different phytoconstituents as a defensive factor in the treatment of diseases caused by free radicals, as in the new era they are conferring less side effects and are compatible to body physiology.

Isoprostanes-Biomarkers of Lipid Peroxidation: Their Utility in Evaluating Oxidative Stress and Analysis

Isoprostanes (IsoPs) are key biomarkers for investigating the role of free radical generation in the pathogenesis of human disorders. To solve IsoPs-related problems with regard to isoprostanes, analytical tools are required. This paper reviews the problems and trends in this field focusing on the methodology for assaying biomarkers in exhaled breath condensate (EBC) samples. A large amount of work has been done in the qualitative and quantitative analysis of IsoPs, but a standardized method has yet to emerge. The methodologies described differ, either in the sample preparation steps or in the detection techniques, or both. Requiring a number of chromatographic steps, the relevant extraction and purification procedures are often critical and time-consuming, and they lead to a substantial loss of target compounds. Recent data show that EBC is a promising non-invasive tool for the evaluation of different diseases. Two main analytical approaches have been adopted for IsoPs measurement: immunological methods and mass spectrometry. The methodologies for the extraction, purification and analysis of IsoPs in EBC samples are presented.

Effects of photooxidation on membrane integrity in Salix nigra seeds

Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas-liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation.

Microglia enhance manganese chloride-induced dopaminergic neurodegeneration: Role of free radical generation

Exposure to elevated levels of manganese has been shown to cause neuronal damage in the midbrain and the development of Parkinsonian symptoms. Activation of microglia and release of neurotoxic factors in particular free radicals are known to contribute to neurodegeneration. We have recently reported that manganese chloride (MnCl2) stimulates microglia to produce reactive oxygen species (ROS). The aim of this study is to determine the role of microglia in the MnCl2-induced degeneration of dopaminergic (DA) neurons that are particularly vulnerable to oxidative insult. MnCl2 (10–300 μM; 7 days) was markedly more effective in damaging DA neurons in the rat mesencephalic neuron–glia cultures than the neuron-enriched (microglia-depleted) cultures. In addition, the microglia-enhanced MnCl2 toxicity was found to be preferential to DA neurons. The microglial enhancement of DA neurotoxicity was further supported by the observation that replenishment of microglia to the neuron-enriched cultures significantly increased the susceptibility of DA neurons to the MnCl2-induced damage. Analysis of the temporal relationship between microglial activation and DA neurodegeneration revealed that MnCl2-stimulated microglial activation preceded DA neurodegeneration. Mechanistically, MnCl2 (10–300 μM) stimulated a concentration- and time-dependent robust production of ROS and moderate production of nitric oxide but no detectable release of tumor necrosis factor-alpha and interleukin-1beta. Application of free radical scavengers including superoxide dismutase/catalase, glutathione, N-acetyl cysteine and an inhibitor of nitric oxide biosynthesis significantly protected DA neurons against the MnCl2-induced degeneration. These results demonstrate that microglial activation and the production of reactive nitrogen and oxygen free radicals promote the MnCl2-induced DA neurodegeneration.

Novel free radical scavengers protect retinal cells and decrease elevated intraocular pressure in a rat ocular hypertension model

Glaucoma is a neurodegenerative disease with damage retinal cells (RC) often associated with elevated intraocular pressure (IOP). Novel free radical scavengers (FRS) with esterified ion chelator and reducing side groups on a methoxypolyethylene glycol backbone (MPs) were evaluated as anti–glaucoma agents capable of both IOP reduction and RC protection.The operated eye of surgical rat glaucoma model received topical MPs or amifostine, a clinical FRS (all agents 20 ml, 0.3 – 100 mM). IOP was measured via Goldmann tonometer. Slit lamp, confocal microscopy and chronic toxicity studies were performed on normal rats (10 or 87 mM MPs, 3x/day for 30 days). 14C MPs were used for pharmacokinetic studies. Intravitreal injection with NMDA (2μL, 10–40mM) to naïve rats induces RC ERG and histological losses in 2 weeks. This damage was challenged with co–administered intravitreal MPs (n=5–6).Topical MPs (3–100 mM), but not amifostine, decreased IOP up to 29.6 % for T1/2s of 1–2 hrs. MPs also caused no acute or chronic ocular/systemic toxicity. 14C topical MPs showed ocular penetration with elimination via urine. MPs also reduced NMDA induced RC loss and A and B waves decreases. In vitro isolated rat and bovine RC assays are currently evaluating the role of free radical generation, elevated intracellular calcium and mitochondrial depolarization in the MPs mechanism of action in vivo.Supported in part by CHRB and AHAF.

Interaction of Measles Virus Vectors with Auger Electron Emitting Radioisotopes.

Background: Viral vectors based on the Edmonston strain of measles virus (MV-Edm) selectively destroy all tumor cell lines tested in vitro. The oncolytic activity of the virus is enhanced by expression of the thyroidal sodium iodide symporter (MV-NIS) that allows selective 131I uptake by infected tumor cells and eliminates myeloma tumor xenografts that are resistant to the parent virus. MV-NIS is being considered for therapy of patients with relapsed or refractory multiple myeloma. Advanced myeloma is associated with significant immunosuppression with the potential risk of uncontrolled virus proliferation. The number of agents with activity against MV is limited. Low energy (Auger) electrons have a short path length and selectively damage cells in which the isotope decays. Thus, we hypothesized that the Auger electron emitting isotope 125I, selectively taken up by cells expressing NIS, can be used to control viral proliferation.Methods: A replication competent MV that expressed both a soluble form of carcinoembryonic antigen (CEA) and NIS (MV-NICE) was rescued and characterized. Cells were infected with MV-NICE or control vectors and exposed to 125I with appropriate controls. CEA expression and viral titers were determined at different time points. The role of free radical generation on virus replication was explored. In vivo control of MV-NICE replication with 125I was attempted.Results: MV-NICE replication in vitro is inhibited by the selective uptake of 125I by cells expressing NIS. Extracellular decay of the isotope has no effect on virus proliferation. Auger electron damage is in part mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125I was not possible under the conditions of the experiment.Conclusion: MV-NICE does not replicate faster in the presence of radiation under our experimental conditions. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo.

Reactive Radicals on Reactive Surfaces: Heterogeneous Processes in Catalysis and Environmental Pollution Control

Many reactions that occur on solid surfaces are mediated by free radicals. A review is presented of both mechanistic and practical investigations in relation to catalysis and environmental applications. The review begins with actual imaging of surface adsorbed reactive radicals using scanning tunnelling microscopy (STM), and then discusses a range of examples, mainly as underpinned by electron spin resonance (ESR) measurements. Included are surface defects and their reactions, studies of the redox behaviour of zeolites, and the use of radicals adsorbed in zeolites as molecular surface probes of diffusion and reactivity within these important materials. Photocatalysis, mainly using TiO2-based materials, is reviewed both from the fundamental perspective and in terms of some practical examples relating to pollution control. Other reactive oxide surfaces are considered, including silica, and the nature of paramagnetic centres that may be induced thereon by a variety of activation procedures. Evidence is presented for the formation of radical species during heterogeneous reactions on metal surfaces. Finally, the role of free radical generation in creating and modifying polymer and nanomolecular systems is discussed, and the health implications of the ability of some solids such as quartz to generate reactive oxygen radicals in contact with biological media.

Inhibitory effects of DA-9601 on ethanol-induced gastrohemorrhagic lesions and gastric xanthine oxidase activity in rats

The exposure of gastric mucosa to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, even acute ulcers. The gastric mucosal lesions accompanied by a significant decrease of gastric blood flow and increase of reactive oxygen species (ROS) implicate a role of xanthine oxidase in ethanol-induced gastric hemorrhagic erosions. DA-9601, a novel antipeptic formulation of extracts of Artemisia asiatica Nakai, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intubation of absolute ethanol (4 g/kg) significantly induced gastrohemorrhagic lesions and lipid peroxidation in the rat stomach. Oral administration of DA-9601 at 40 mg/kg body weight significantly reduced ethanol-induced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of DA-9601 on alcohol-induced xanthine oxidase-type conversion and enzyme activity. The results suggest that alcohol-induced gastric mucosal damage may be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and that the preventive effect of DA-9601 on gastrohemorrhagic lesions would result from its inhibitory action against xanthine oxidase and oxidative stress in alcohol-treated rats.

Visualizing Superoxide Production in Normal and Diabetic Rat Islets of Langerhans

Oxygen free radicals have been implicated in beta-cell dysfunction and apoptosis associated with type 1 and type 2 diabetes mellitus. The roles of free radicals in diabetes have thus far been defined indirectly by monitoring oxidative tissue damage and the effects of antioxidants, free radical scavengers, and overexpression of superoxide dismutase. We employed the superoxide-mediated oxidation of hydroethidine to ethidium to dynamically and directly assess the relative rates of mitochondrial superoxide anion generation in isolated islets in response to glucose stimulation. Superoxide content of isolated islets increased in response to glucose stimulation. We next compared the oxyradical levels in Zucker lean control and Zucker diabetic fatty rat islets by digital imaging microfluorometry. The superoxide content of Zucker diabetic fatty islets was significantly higher than Zucker lean control islets under resting conditions, relatively insensitive to elevated glucose concentrations, and correlated temporally with a decrease in glucose-induced hyperpolarization of the mitochondrial membrane. Importantly, superoxide levels were elevated in islets from young, pre-diabetic Zucker diabetic fatty animals. Overproduction of superoxide was associated with perturbed mitochondrial morphology and may contribute to abnormal glucose signaling found in the Zucker diabetic fatty model of type 2 diabetes mellitus.

Experimental study of the effect of adrenaline tolerance on intestinal ischaemia-reperfusion.

Adrenaline tolerance improves survival in animal models of shock. The purpose of this study was to determine the effects of adrenaline tolerance on intestinal ischaemia-reperfusion in a mouse model. Adrenaline tolerance was developed by injecting intravenous adrenaline, gradually increasing the dose to 2 mg/kg over 5 days. In experimental animals the superior mesenteric artery was clamped for 120 min and then released. Evans blue dye was given intravenously to all animals to quantify pulmonary microvascular injury. Some 60 min after clamp release, the animals were killed and the effects of reperfusion assessed on tissue samples. Evans blue dye concentrations were significantly higher in animals with intestinal ischaemia-reperfusion than in those having sham intestinal ischaemia-reperfusion or in adrenaline-tolerant mice having intestinal ischaemia-reperfusion or sham ischaemia-reperfusion (P< 0.01). Malonyldialdehyde levels increased significantly in the lung in the intestinal ischaemia-reperfusion group compared with those in the sham ischaemia-reperfusion group (P< 0.001 for liver, lung and small intestine), whereas there was no difference in adrenaline-tolerant animals. There was no significant change induced by adrenaline tolerance in myeloperoxidase levels in any organ. Adrenaline tolerance reduced the lung permeability caused by intestinal ischaemia-reperfusion. Catecholamines may play a role in free radical generation induced by ischaemia-reperfusion.

Urinary F2-isoprostanes formation in kidney transplantation.

Oxygen free-radical mediated lipid peroxidation has been implicated in many diseases such as chronic renal failure, hemodialysis and chronic kidney transplant rejection. However, insight into the role of free radical generation in kidney transplantation has been constrained by the limitations of current indexes of oxidant stress in vivo. Isoprostaglandin F2alpha type-III (iPF2alpha-III, formerly known as 8-iso-prostaglandin F2alpha) is emerging as a reliable marker of oxidant stress in vivo. The purpose of our study was to investigate iPF2alpha-III formation as an index of lipid peroxidation in the 5 d following kidney transplantation. Urinary iPF2alpha-III measurements were performed by enzyme immunoassay from day I to 5 in 11 patients undergoing kidney transplantation. Results were compared with 11 healthy volunteers matched in sex, age and cigarette smoking. Urinary excretion of iPF2alpha-III at day 1 did not significantly differ between control and transplant group (111 +/- 17 vs. 92 +/- 10 pM/ mM creatinine, respectively, NS). Urinary iPF2alpha-III levels did not differ between day 1 to 5, and were not correlated to cold ischaemia time. Our study shows no evidence of enhanced lipid peroxidation in the first 5 d following kidney transplantation.

Metal toxicity in yeasts and the role of oxidative stress

Publisher Summary Metal toxicity continues to be a major problem at several levels, and there is a pressing need for the deleterious effects of metals at the cellular and molecular level. This chapter discusses a major role of free radical generation in the toxicities of many metals. A number of mechanisms have been proposed to underlie metal induced Reactive Oxygen Species (ROS) generation, and these mechanisms tend to differ between metals according principally to whether they are redox active or inactive. Several yeast groups are currently focusing on metal homeostasis, which may have steered some attention away from exploiting yeasts for direct studies of metal toxicity. The extent of the contribution to whole-cell metal toxicity made by damage to each potential target has not been determined, and this is not helped by the fact that almost all studies have tended to focus on one type of target and/or whole cells exclusively. The evidence to date indicates that each of the major cellular macromolecules (lipids, proteins, and nucleic acid) can be a target for metal toxicity. The relative importance of membrane damage in determining the metal sensitivities of different yeasts may depend on the organism's lipid compositions, specifically their polyunsaturated fatty acid contents.

Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant α-lipoic acid

Free radical generation is increasingly implicated in a variety of pathological processes, including drug toxicity. Recently, a number of studies have demonstrated the ability of gentamicin to facilitate the generation of radical species both in vivo and in vitro, which suggests that this process plays an important role in aminoglycoside-induced ototoxicity. Free radical scavengers are compounds capable of inactivating free radicals, thereby attenuating their tissue damaging capacity. In this study we have determined the ability of the powerful free radical scavenger α-lipoic acid (100 mg/kg/day) to attenuate the cochlear damage induced by a highly ototoxic regimen of the aminoglycoside amikacin (450 mg/kg/day, i.m.). Experiments were carried out on pigmented guinea pigs initially weighing 200–250 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every 5 days, by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving α-lipoic acid in combination with amikacin demonstrated a significantly less severe elevation in CAP thresholds compared with animals receiving amikacin alone ( P<0.001; t-test). These results provide further evidence of the recently reported intrinsic role of free radical generation in aminoglycoside ototoxicity, and highlight a potential clinical therapeutic use of α-lipoic acid in the management of patients undergoing aminoglycoside treatment.

Polyphenolic Antioxidant (‐)‐Epigallocatechin‐3‐Gallate from Green Tea Reduces UVB‐lnduced Inflammatory Responses and Infiltration of Leukocytes in Human Skin

Identification of natural products capable of affording protection against UVB radiation-induced inflammatory responses and generation of oxidative stress may have important human health implications. The UVB exposure-induced skin injury and oxidative stress has been associated with a variety of skin disease conditions including photoaging, inflammation and cancer. Tea is a popular beverage consumed worldwide. In several mouse skin models, topical application as well as oral consumption of green tea has been shown to afford protection against chemical and UVB-induced carcinogenesis and inflammatory responses. In the present study, we investigated in human skin, whether topical application of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent in green tea, inhibits UVB-induced infiltration of leukocytes (macrophage/neutrophils), a potential source of generation of reactive oxygen species (ROS), and generation of prostaglandin (PG) metabolites. Human subjects were UVB irradiated on sun-protected skin to four times their minimal erythema dosage (MED) and skin biopsies or keratomes were obtained either 24 h or 48 h later. We found that topical application of EGCG (3 mg/2.5 cm2) before UVB (4 MED) exposure to human skin significantly blocked UVB-induced infiltration of leukocytes and reduced myeloperoxidase activity. These infiltrating leukocytes are considered to be the major source of generation of ROS. In the same set of experiments we found that topical application of EGCG before UVB exposure decreased UVB-induced erythema. In additional experiments, we found that microsomes from EGCG pretreated human skin and exposed to UVB, compared to UVB exposure alone, produced significantly reduced PG metabolites, particularly PGE2. The PG metabolites play a critical role in free radical generation and skin tumor promotion in multistage skin carcinogenesis. Careful microscopic examination of skin sections, stained with hematoxylin and eosin, under higher magnification (x400) also revealed that EGCG pretreated and UVB-exposed human skin contained fewer dead cells in the epidermis with comparison to nonpretreated UVB-exposed skin. Taken together, our data demonstrate that EGCG has the potential to block the UVB-induced infiltration of leukocytes and the subsequent generation of ROS in human skin. This may explain the possible mechanism involved in anti-inflammatory effects of green tea. We suggest that EGCG may be useful as a topical agent for protection against UVB-induced ROS-associated inflammatory dermatoses, photoaging and photocarcinogenesis. Further studies are warranted in this direction.

Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines.

Anthralin is the most common therapeutic agent among a small number of pro-oxidant, 9-anthrones effective in the topical treatment of psoriasis. However, the usefulness of this drug is diminished by toxic side effects, including skin irritation and inflammation. The activities of anthralin are believed to be mediated by the generation of reactive oxygen intermediates and anthrone radicals produced in the skin. In this study, the dermal inflammatory response to anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by anthralin coincided with the elevation of cytokine mRNA expression in the skin, including interleukin-6, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, and tumor necrosis factor alpha at 24 h post challenge. The role of free radical generation in ear swelling and cytokine modulation were examined by systemic administration of cell permeable and impermeable antioxidants before anthralin challenge. Superoxide dismutase and alpha-tocopherol acetate, but not the glutathione precursor N-acetyl cysteine, were effective inhibitors of anthralin-induced ear swelling and cytokine elevation. Maximum inflammatory cell infiltration occurred 72-96 h post anthralin challenge and was also reduced by antioxidants. These data suggest that oxidative stress, generated at the site of anthralin treatment, alters the expression of dermal chemokines and other cytokines resulting in the recruitment of inflammatory cells. Systemic antioxidant administration may provide opportunities for therapeutic intervention against anthralin-associated toxicities.