Antioxidant Defense System Of Cells Research Articles

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in H2О2-induced oxidative stress (0.1mM H2О2), thus showing an effective in vitro protection.In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol − induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury.

Prochlorperazine interaction with melanin and melanocytes.

Prochlorperazine is a phenothiazine-class antipsychotic drug usually used to treat nausea, vomiting and schizophrenia. Phenothiazine derivatives have been known to cause serious side effects, like extrapyramidal symptoms, but also skin disorders which mechanism has not been fully established. The aim of this study was to examine the interaction between prochlorperazine and melanin as well as to estimate the effect of prochlorperazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. We have demonstrated that prochlorperazine forms stable complexes with melanin, characterized by two classes of independent binding sites with the association constants K1∼106 M-1 and K2∼102 M-1. It has been shown that prochlorperazine induces concentration-dependent loss in cell viability. The value of EC50 was calculated to be 18.49 μM. Prochlorperazine in a concentration of 0.001 μM stimulated melanogenesis, while in concentrations 1.0 and 10.0 μM melanization process was inhibited. Furthermore, the drug in concentrations of 0.1, 1.0 and 10.0 μM caused changes in cellular antioxidant defense system, what indicated the induction of oxidative stress. The observed changes in cell viability, melanization and antioxidant defense system in normal human melanocytes after prochlorperazine treatment may explain a potential role of melanin, oxidative stress and melanocytes in mechanisms of undesirable side effects after accumulation of this drug in pigmented tissues.

426 - Lack of Manganese Superoxide Dismutase Impairs Brown Adipose Tissue Function in Mice

Manganese superoxide dismutase (MnSOD) is an essential member of the cell antioxidant defense system, since it efficiently catalyzes the dismutation of superoxide radical (O2–) to H2O2 and O2 in the mitochondrial matrix. Previous studies from our group have revealed that MnSOD deletion in adipocytes confers resistance to HFD-induced obesity and insulin resistance, due in part to enhanced fatty acid oxidation, mitochondrial respiration and mitochondrial biogenesis in WAT, but resulted in brown adipose tissue (BAT) atrophy and cold intolerance. In order to gain insights into the mechanisms behind BAT atrophy in adipocytes-specific MnSOD knockout mice, we generated mice with BAT-specific deletion of MnSOD using Ucp1-cre line (USod2 KO mice). As expected MnSOD protein was absent from BAT but not from WAT of USod2 KO mice. In addition, a significant decrease in adipogenic markers, such as PPARγ and FABP-4 was observed in BAT of KO mice compared to BAT of control mice. Although no changes were observed in body weight and body composition, USod2 KO mice were cold intolerant, had lower metabolic rate and reduced heat production. Despite lower energy expenditure, USod2 KO mice have improved insulin and glucose tolerance. Taken together, these results indicate that lack of MnSOD in BAT impairs its function.

ПРООКСИДАНТНО–АНТИОКСИДАНТНИЙ СТАТУС КОРІВ ЗА ГОНАДОПАТІЙ

Situational increase in the concentration of free oxide in the body for a reduction of antioxidant defense is accompanied by the development of pathological processes.One of the major cell damage by free radicals is the destruction of the fatty acids that make up cell membranes (lipid peroxidation). Peroxidation of lipids of biological membranes causes a disturbance of the barrier function and reduces the enzymatic activity; disintegrates receptor binding and vesicular transport. This leads to disruption of cellular activity, accelerated apoptosis degeneration, necrobiosis, atrophy and necrosis.The damaging effect of oxygen radicals in the cell antioxidant defense system opposed., protection function is performed by enzymes – superoxide dismutase, catalase, glutathione reductase, and low molecular weight non–enzymatic antioxidants (carotenoids, tocopherol), water soluble vitamins (ascorbic acid).Thus, the oxidation of lipid structures underlying the development of many diseases, including pathologies animal reproductive organs.Among the disorders of the reproductive function in cows is quite common gonadopathy such as gonadodystrophy, hypogonadism and hypoluteolisis on background endometritis (diorganspathology).The emergence and development of ovarian pathologies cows hypothetically can be supplemented by the existence of violations, failures in the prooxidant–antioxidant system, as the basis of these pathologies is a violation tropism, of complex mechanisms for metabolism and preserve cell structure and ovarian tissue.To determine the concentration of free oxide derivatives and antioxidant protection status in cows for ovariodystrophy, hypogonadism and diorgan pathology (endometritis↔hypoluteolisis) presents the materials the article.It is found that for cows ovarian pathologies compared to animals with the normal physiological state gonads malondialdehyde erythrocytes in blood was significantly increased by 10.4 –23.2 mm/l (25.3 – 56.8%), catalase activity was reduced to 13–14,4 m / H2O2 / l–min (56.9– 91.1%), reduced glutathione was reduced to 0.68–0.8 (16.1–19.1%).Installed status data of the antioxidant system in cows with gonadopathy show quite important determinant role in the genesis of ovarian pathologies.

An integrative view of cisplatin-induced renal and cardiac toxicities: Molecular mechanisms, current treatment challenges and potential protective measures.

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell's antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies including combination therapy with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide.

Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline.

Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders. One of the factors influencing the photosensitivity reactions is the melanin content in melanocytes. In this study, the impact of doxycycline and UVA irradiation on cell viability, melanogenesis and antioxidant defense system in cultured normal human epidermal melanocytes (HEMn-DP) was examined. The exposure of cells to doxycycline and UVA radiation resulted in concentration-dependent loss in melanocytes viability and induced melanin biosynthesis. Significant changes were stated in cellular antioxidant enzymes activity: SOD, CAT and GPx, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation.

Antioxidant nanozyme: a facile synthesis and evaluation of the reactive oxygen species scavenging potential of nanoceria encapsulated albumin nanoparticles.

Several diseases and disorders, including cancer are endorsed by excessive oxidative stress caused due to the incomplete removal of reactive oxygen species (ROS) by the antioxidant defense system of the body. Therefore, present interest among the scientific community lies in the development of a highly stable, biocompatible artificial enzymatic system that possesses a high ROS scavenging activity over a period of time. In recent years, catalytic nanoparticles emerged as a potential candidate in the field of nanomedicine. Due to their inherent catalytic properties, they are exploited as an artificial enzyme (nanozyme), to reinstate or correct aberrant enzymatic activities in patients. Among them, cerium oxide nanoparticles/nanoceria (CNPs) emerged as a potent artificial redox enzyme, mimicking the activity of superoxide dismutase (SOD) and catalase and endure a tremendous ROS scavenging potential as depicted in a surfeit of human cell lines and animal models. In the present article, a facile synthesis of biocompatible nanoceria encapsulated albumin nanoparticles (BCNPs) via desolvation technique that lead to the abatement of intracellular ROS is reported. Physico-chemical characterizations of as-prepared BCNPs corroborate the formation of a highly monodispersed, spherical and stable aqueous delivery system. Interestingly, such entrapment does not affect the enzyme mimetic activity of CNPs, as demonstrated by SOD assay. The biocompatibility and ROS scavenging potential of BCNPs were further assessed in vitro against human lung epithelial cells by cell viability assay and flow cytometric analysis, respectively. The quantitative and qualitative assessments of cellular uptake of BCNPs were done by inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) analysis. Furthermore, the BCNPs preserve the cell's antioxidant defense system and protect them from oxidant-mediated apoptosis as confirmed by semi-quantitative RT-PCR analysis. Thus, the as-prepared BCNPs could provide an opportunity to be utilized as a potential candidate against ROS induced diseases and disorders.

Experimental liver protection of n-butanolic extract of Astragalus monspessulanus L. on carbon tetrachloride model of toxicity in rat

ObjectiveTo investigate the hepatoprotective potential of n-butanolic extract of Astragalus monspessulanus L. (EAM) against in-vitro/in-vivo carbon tetrachloride (CCl4)-induced liver damage in rats. Silymarin was used as a positive control.Methods and resultsThe in-vitro experiments were carried out in primary isolated rat hepatocytes first incubated with CCl4 (86 µmol/l). Hepatic injury was discerned by a decrease in cell viability and cell glutathione (GSH) levels, an increase in lactate dehydrogenase leakage into the medium, and an elevation in malondialdehyde (MDA) quantity. Cell pre-incubation with EAM (1 µg/ml and 10 µg/ml) significantly ameliorated the CCl4-induced liver damage. In-vivo rats were challenged orally with CCl4 (10% solution in olive oil) alone and after 7 days pre-treatment with EAM (100 mg/kg body weight per day, oral gavage). CCl4 damage was judged by an increased production of MDA, depletion of cell GSH, and a decrease in cell antioxidant defense system. EAM pre-treatment normalizes the activities of the antioxidant enzymes and the levels of GSH and MDA. These data are supported by the histopathological examination.ConclusionThese results indicate that EAM has a similar significant protective effect, in vitro and in vivo, against CCl4 induced hepatotoxicity in rat as silymarin.This may be due to its antioxidant and membrane stabilizing properties.

Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine

Chlorpromazine is used in the treatment of schizophrenia and psychotic disorders and belongs to phenothiazine class of neuroleptic drugs. It shows severe side effects such as extrapyramidal symptoms as well as ocular and skin disorders, but the mechanism is still not fully established. The aim of this study was to examine the effect of chlorpromazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been demonstrated that chlorpromazine induces concentration-dependent loss in cell viability. The value of EC50 was calculated to be 2.53μM. Chlorpromazine in lower concentrations (0.0001, 0.001 and 0.01μM) increased the melanin and microphthalmia-associated transcription factor (MITF) content and tyrosinase activity, while changes of antioxidant enzymes activity were not observed. It suggests that long-term chlorpromazine therapy, even with low drug doses, may lead to hyperpigmentation disorders in skin and/or eye. The use of the analyzed drug in higher concentrations (0.1 and 1.0μM) caused significant alterations of antioxidant enzymes activity in normal melanocytes, what may explain a potential role of chlorpromazine in the depletion of cellular antioxidant status leading to other adverse effects associated with the high-dose and/or long-term therapy.

EHMTI-0241. Association between migraine and sod1 and sod2 genes polymorphisms: the biobim study

Several studies suggest that an increased oxidative stress is a key event in migraine, especially in the form with aura. One of the most efficient first line antioxidant defense system of cells exposed to oxygen is Superoxide Dismutase (SOD) system. The SOD1 gene presents a polymorphism (A/C substitution - rs2234694) resulting in lower serum activitiy in subjects carrying CC genotype. SOD2 gene presents a polymorphism (C/T transition -rs4880 – Ala16Val) which leads to an instable mRNA and reduced transport of the enzyme in TT genotype carriers.

Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity

Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X-ray absorption near-edge structure (XANES) was employed to assess the chemical state of intracellular silver. The toxic potential of Ag NPs and Ag+ was evaluated by cell viability, reactive oxygen species (ROS) production and live–dead cell staining. The results suggest that cellular uptake of Ag NPs involves lipid-raft-mediated endocytosis and energy-independent diffusion. The degradation study shows that Ag NPs taken up into cells dissolved quickly and XANES results directly indicated that the internalized Ag was oxidized to Ag−O− species and then stabilized in silver−sulfur (Ag−S−) bonds within the cells. Subsequent cytotoxicity studies show that Ag NPs decrease cell viability and increase ROS production. Pre-incubation with N-acetyl-l-cysteine, an efficient antioxidant and Ag+ chelator, diminished the cytotoxicity caused by Ag NPs or Ag+ exposure. Our study suggests that the cytotoxicity mechanism of Ag NPs is related to the intracellular release of silver ions, followed by their binding to SH-groups, presumably coming from amino acids or proteins, and affecting protein functions and the antioxidant defense system of cells.

Heavy-metal-induced reactive oxygen species: phytotoxicity and physicochemical changes in plants.

As a result of the industrial revolution, anthropogenic activities have enhanced there distribution of many toxic heavy metals from the earth's crust to different environmental compartments. Environmental pollution by toxic heavy metals is increasing worldwide, and poses a rising threat to both the environment and to human health.Plants are exposed to heavy metals from various sources: mining and refining of ores, fertilizer and pesticide applications, battery chemicals, disposal of solid wastes(including sewage sludge), irrigation with wastewater, vehicular exhaust emissions and adjacent industrial activity.Heavy metals induce various morphological, physiological, and biochemical dysfunctions in plants, either directly or indirectly, and cause various damaging effects. The most frequently documented and earliest consequence of heavy metal toxicity in plants cells is the overproduction of ROS. Unlike redox-active metals such as iron and copper, heavy metals (e.g, Pb, Cd, Ni, AI, Mn and Zn) cannot generate ROS directly by participating in biological redox reactions such as Haber Weiss/Fenton reactions. However, these metals induce ROS generation via different indirect mechanisms, such as stimulating the activity of NADPH oxidases, displacing essential cations from specific binding sites of enzymes and inhibiting enzymatic activities from their affinity for -SH groups on the enzyme.Under normal conditions, ROS play several essential roles in regulating the expression of different genes. Reactive oxygen species control numerous processes like the cell cycle, plant growth, abiotic stress responses, systemic signalling, programmed cell death, pathogen defence and development. Enhanced generation of these species from heavy metal toxicity deteriorates the intrinsic antioxidant defense system of cells, and causes oxidative stress. Cells with oxidative stress display various chemical,biological and physiological toxic symptoms as a result of the interaction between ROS and biomolecules. Heavy-metal-induced ROS cause lipid peroxidation, membrane dismantling and damage to DNA, protein and carbohydrates. Plants have very well-organized defense systems, consisting of enzymatic and non-enzymatic antioxidation processes. The primary defense mechanism for heavy metal detoxification is the reduced absorption of these metals into plants or their sequestration in root cells.Secondary heavy metal tolerance mechanisms include activation of antioxidant enzymes and the binding of heavy metals by phytochelatins, glutathione and amino acids. These defense systems work in combination to manage the cascades of oxidative stress and to defend plant cells from the toxic effects of ROS.In this review, we summarized the biochemiCal processes involved in the over production of ROS as an aftermath to heavy metal exposure. We also described the ROS scavenging process that is associated with the antioxidant defense machinery.Despite considerable progress in understanding the biochemistry of ROS overproduction and scavenging, we still lack in-depth studies on the parameters associated with heavy metal exclusion and tolerance capacity of plants. For example, data about the role of glutathione-glutaredoxin-thioredoxin system in ROS detoxification in plant cells are scarce. Moreover, how ROS mediate glutathionylation (redox signalling)is still not completely understood. Similarly, induction of glutathione and phytochelatins under oxidative stress is very well reported, but it is still unexplained that some studied compounds are not involved in the detoxification mechanisms. Moreover,although the role of metal transporters and gene expression is well established for a few metals and plants, much more research is needed. Eventually, when results for more metals and plants are available, the mechanism of the biochemical and genetic basis of heavy metal detoxification in plants will be better understood. Moreover, by using recently developed genetic and biotechnological tools it may be possible to produce plants that have traits desirable for imparting heavy metal tolerance.

Effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with Plasmodium yoelii nigeriensis

Reactive oxygen species are mediators of tissue injury and are involved in malaria infection. In this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during Plasmodium yoelii nigeriensis (P. yoelii) infection, and treatment with chloroquine (CQ), methylene blue (MB) or artemether (ART) in mice. P. yoelii infection caused a significant (p < 0.05) increase in oxidative stress as evidenced by the elevated level of malondialdehyde. This was followed by a significant decrease (p < 0.05) in hepatic antioxidant defence indices, viz. reduced glutathione (GSH) and glutathione-S-transferase (GST). Also, the red cell catalase activity was significantly (p < 0.05) lower in malaria infection, while there was no significant difference (p > 0.05) in the superoxide dismutase (SOD) activity of infected mice when compared to untreated normal. Treatment of infected mice with the three antimalarials showed that the drugs suppressed the parasitaemia in the order CQ > ART > MB. CQ, MB and ART treatment of infected mice caused a significant (p < 0.05) increase in the levels of hepatic GSH and GST. Specifically, CQ, MB and ART increased the levels of hepatic GSH by 108, 124 and 98 %, respectively, at day 6. Also, ART treatment of infected mice significantly (p < 0.05) elevated the red cell SOD level by 200 % at day 3. Taken together, the findings suggest that the antimalarial effect of CQ, MB and ART countered the P. yoelii-induced oxidative stress leading to the elevation of enzymatic and non-enzymatic antioxidants in the host system.

Hepatoprotective and Antioxidant Effects of Saponarin, Isolated fromGypsophila trichotomaWend. on Paracetamol-Induced Liver Damage in Rats

The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 μmol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60–0.006 μg/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected. Saponarin pretreatment resulted in significant increase in cell antioxidant defence system and GSH levels and decrease in lipid peroxidation. The biochemical changes are in good correlation with the histopathological data. Protective activity of saponarin was similar to the activity of positive control silymarin. On the basis of these results, it can be concluded that saponarin exerts antioxidant and hepatoprotective activity against paracetamol liver injury in vitro/in vivo.

Estrés oxidativo: origen, evolución y consecuencias de la toxicidad del oxígeno

El oxígeno es un elemento que presenta un perfil con doble efecto fisiológico; es esencial para el desarrollo de la vida aerobia y posee efectos tóxicos inherentes a su estructura. Del oxígeno se derivan moléculas inestables denominadas radicales libres que pueden causar daño a nivel celular, cuando se pierde el equilibrio entre dichas moléculas y el sistema de defensa antioxidante que poseen los seres vivos, generando así lo que se denomina estrés oxidativo. Dicho mecanismo posee una estrecha relación con el desarrollo y evolución de una gran variedad de procesos degenerativos, enfermedades y síndromes. Su estudio se ha centrado principalmente en el conocimiento de los mecanismos de su génesis y las formas de; atenuar, disminuir o contrarrestarlas, por medio de los sistemas de defensa antioxidante que posee la célula y la forma de controlar los radicales libres que se generan de forma normal y continua en el organismo resultado de algunos procesos celulares como el relacionado con el metabolismo oxidativo de la mitocondria, proceso necesario para la obtención de ATP.

Heavy Metal Induced Antioxidant Defense System of Green Microalgae and its Effective Role in Phycoremediation of Tannery Effluent

Investigation of tannery effluent toxicology in green microalgae is of great importance from ecological point of view, because heavy metal has become a major contaminant in recent years. The present study determined the effect of various concentrations (0, 10, 25, 50, 75 and 100%) of heavy metals containing tannery effluent on cell growth and antioxidant defense system of two green microalgae. Treatment with effluent induced accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX). Lower tannery effluent concentrations increased algal growth, whereas higher concentration suppressed the growth and photosynthetic content. Both strains of the microalgae had proven effective in removing heavy metals from aqueous solutions with the highest removal efficiency being near 100% and it can be used for phycoremediation of wastewater in large scale.

Mentha piperita as a pivotal neuro-protective agent against gamma irradiation induced DNA fragmentation and apoptosis

Ionizing radiation is classified as a potent carcinogen, and its injury to living cells, in particular to DNA, is due to oxidative stress enhancing apoptotic cell death. Our present study aimed to characterize and semi-quantify the radiation-induced apoptosis in CNS and the activity of Mentha extracts as neuron-protective agent. Our results through flow cytometry exhibited the significant disturbance and arrest in cell cycle in % of M1: SubG1 phase, M2: G0/1 phase of diploid cycle, M3: S phase and M4: G2/M phase of cell cycle in brain tissue (p<0.05). Significant increase in % of apoptosis and P53 protein expression as apoptotic biomarkers were coincided with significant decrease in Bcl(2) as an anti-apoptotic marker. The biochemical analysis recorded a significant decrease in the levels of reduced glutathione, superoxide dismutase, deoxyribonucleic acid (DNA) and ribonucleic acid contents. Moreover, numerous histopathological alterations were detected in brain tissues of gamma irradiated mice such as signs of chromatolysis in pyramidal cells of cortex, nuclear vacuolation, numerous apoptotic cell, and neural degeneration. On the other hand, gamma irradiated mice pretreated with Mentha extract showed largely an improvement in all the above tested parameters through a homeostatic state for the content of brain apoptosis and stabilization of DNA cycle with a distinct improvement in cell cycle analysis and antioxidant defense system. Furthermore, the aforementioned effects of Mentha extracts through down-regulation of P53 expression and up-regulation of Bcl(2) domain protected brain structure from extensive damage. Therefore, Mentha extract seems to have a significant role to ameliorate the neuronal injury induced by gamma irradiation.

Redox active secondary metabolites

Various secondary metabolites from plants, bacteria and fungi are redox active and able to modulate the intracellular redox equilibrium in living cells. Many of these compounds behave as antioxidants, yet some of them also cause oxidative modifications, which may ultimately result in cell death. Natural isothiocyanates and xanthohumol, for instance, appear to act specifically in and against cells with a disturbed redox balance, such as certain cancer cells. Similarly, polysulfane and pyocyanin derivatives employ the glutathione antioxidant defense system of cells to generate a lethal cocktail of reactive oxygen species. Together, these redox-modulating metabolites provide promising new leads to target selectively certain cancer cells. They may also be useful in the treatment of autoinflammatory diseases.

Chromium (VI) Can Activate and Impair Antioxidant Defense System

The changes in glutathione-dependent cycle enzymes and catalase activities under Cr(VI)-induced oxidative stress were investigated in two distinct cell lines: L-41-human epithelial-like cells and HLF-fetal human diploid lung fibroblasts, which differ in tissue origin, proliferation, and antioxidant enzymes activities. The chromium concentrations from 1 to 5μM cause nontoxic effects and activate antioxidant enzymes to overcome oxidative stress. In spite of some differences in the endogenous antioxidant activities, both cell lines reveal the same range of toxic concentrations (20-30μM). The irreversible inhibition of glutathione-dependent antioxidant enzymes develops under toxic concentrations and serves as a marker of toxicity. The endogenous antioxidant activity influences time-dependent expression of Cr(VI) toxicity and the dynamics of antioxidant enzymes activity under nontoxic conditions. The cell antioxidant defense system is an important marker of the cell adaptive capacity under nontoxic and toxic conditions.

Effect of copper intoxication on rat liver proteasome activity: Relationship with oxidative stress

Copper toxicity is associated with formation of reactive oxygen species, which are capable to oxidize proteins. The selective removal of the latter by the 20S proteasome is considered an essential part of the cell antioxidant defense system. The aim of the present study was to investigate whether peptidase activities of rat liver proteasomes were affected by chronic (40 mg CuSO(4)/rat/daily with the drinking water for 2 weeks) and acute (20 mg/kg CuSO(4), s.c.) copper treatment. To evaluate the role of proteasome, its inhibitor MG132 was also used. The degree of copper-induced oxidative stress (OS), established by measuring lipid peroxidation, protein oxidation, and cellular glutathione level, as well as activities of antioxidant enzymes--catalase, superoxide dismutase, and gultathionine peroxidase, depended on the mode of copper administration. Chronic copper administration (mild oxidative stress) did not affect proteasome activities, whereas acute copper treatment (severe oxidative stress) caused a decline in chymotryptic- and tryptic-like activities. The treatment of copper-loaded animals with MG132 did not change copper-induced alterations in the tested indices, except an additional increase in protein oxidation and inhibition of glutathionine peroxidase activity. The results suggested that the in vivo copper-induced oxidative stress was associated with changes in the catalytic activity of proteasome.