Intracellular Oxidant Production Research Articles

Gastrodin protects retinal ganglion cells from ischemic injury by activating phosphatidylinositol 3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/AKT/Nrf2) signaling pathway

ABSTRACT Glaucoma is a progressive optic neuropathy and improper treatment may cause irreversible damage to visual function. Gastrodin is an effective active substance extracted from Gastrodia elata and possesses antioxidant as well as anti-inflammatory properties. However, the therapeutic potential of gastrodin for retinal ischemia/reperfusion (I/R) injury remains unclear. We adopted oxygen and glucose deprivation/reoxygenation (OGD/R) to induce R28 cells with the aim of simulating glaucomatous neurodegeneration. CCK-8 analysis and TUNEL were applied for examining cell proliferation and apoptosis . In addition, RT-qPCR and ELISA were performed to test the releases of inflammatory factors in cells . Related indicators of intracellular oxidative stress and ROS production were detected by corresponding kits. Moreover, western blot was applied to assay the expressions of PI3K/AKT/Nrf2 pathway-related proteins. OGD/R induction contributed to the decreased cell viability and reduced Bcl-2 protein expression, while the protein contents of Bax, Cyto-C, c-caspase 9 and c-PARP as well as ROS production were ascended. The co-treatment of hypoxia and gastrodin greatly improved R28 cell viability but effectively suppressed cell apoptosis, ROS level and the releases of OGD/R-induced inflammatory factors as well as oxidative stress. In addition, OGD/R stimulation reduced Nrf2, accompanied by a decrease in the phosphorylation levels of PI3K and AKT. Gastrodin significantly promoted the activation of PI3K/AKT/Nrf2 signaling pathway in R28 cells, which was then counteracted by PI3K/AKT inhibitors. In conclusion, the present study suggested that gastrodin has a protective effect on OGD/R-induced R28 cell injury, which is achieved through the activation of the PI3K/AKT/Nrf2 signaling pathway.

Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction.

Diet-related obesity is associated with increased intestinal hyperpermeability. High dietary fat intake causes an increase in colonic bile acids (BAs), particularly deoxycholic acid (DCA). We hypothesize that DCA modulates the gene expression of multiple cell junction pathways and increases intestinal permeability. With a human Caco-2 cell intestinal model, we used cell proliferation, PCR array, biochemical, and immunofluorescent assays to examine the impact of DCA on the integrity of the intestinal barrier and gene expression. The Caco-2 cells were grown in monolayers and challenged with DCA at physiological, sub-mM, concentrations. DCA increased transcellular and paracellular permeability (>20%). Similarly, DCA increased intracellular reactive oxidative species production (>100%) and accompanied a decrease (>40%) in extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Moreover, the mRNA levels of 23 genes related to the epithelial barrier (tight junction, focal adhesion, gap junction, and adherens junction pathways) were decreased (>40%) in (0.25 mM) DCA-treated Caco-2 cells compared to untreated cells. Finally, we demonstrated that DCA decreased (>58%) the protein content of occludin present at the cellular tight junctions and the nucleus of epithelial cells. Collectively, DCA decreases the gene expression of multiple pathways related to cell junctions and increases permeability in a human intestinal barrier model.

Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction in Caco-2 Cell Monolayers

ObjectivesDiet-related obesity is associated with an increased risk of developing intestinal hyperpermeability. High dietary fat intake causes an increase in colonic bile acids (BAs), particularly deoxycholic acid (DCA, secondary BA), which may disrupt the intestinal epithelial barrier. To determine the potential role of bile acids in barrier dysfunction, we hypothesize that DCA modulates the gene expression in multiple cell junction pathways and increases intestinal permeability. MethodsWith a Caco-2 cell intestinal barrier model, we used cell proliferation, PCR array, biochemical, western blotting and immunofluorescent assays to examine the impact of DCA on the integrity of intestinal barrier and gene expression. ResultsHuman intestinal Caco-2 cells were grown in monolayers and challenged with DCA at physiological concentrations (sub mM levels). DCA increased transcellular and paracellular permeability (>30%) via transepithelial electrical resistance and phenol red flux measurements. Similarly, DCA increased intracellular reactive oxidative species production (>1-fold) and accompanied a modification of cellular p38 and ERK1/2 signaling pathways. Further characterization of underlying genes related to epithelial barrier with PCR array analysis identified that 23 genes (in tight junction, focal adhesion, gap junction and adhere junction pathways) were decreased at least 40% in (0.25 mM) DCA-treated Caco-2 cells when compared to untreated cells. Finally, we demonstrated that DCA decreased the protein levels of occludin gene at both cellular tight junction and nucleus in epithelial cells. ConclusionsCollectively, our data suggest that at physiological concentrations, DCA alters the gene expression of multiple pathways related to cell junctions and increases permeability in a Caco-2 intestinal barrier model. These molecular events may represent the underlying mechanistic pathways that are responsible for DCA-induced transcellular and paracellular permeation. Funding SourcesThis work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062-51,000-056–00D.

The effect of antihistamines drugs on the functional activity of neutrophils

Allergic inflammation is accompanied by stimulation of neutrophils with an increase in the formation of reactive oxygen species. The antioxidant effectiveness of some antihistamines is known, which reduces the risk of damage to surrounding tissues with the participation of these cells. Objective of the study: to determine the degree of various generations antihistamines influence on the death and enzymatic activity of neutrophils. The effect of the first antihistamines (diphenhydramine, clemastine) and second (lorata-dine, desloratadine) generations and the hormonal drug dexameth-asone on cell viability, the formation of active oxygen metabolites, enzyme activity, the amount of cationic proteins, and cytokine production by neutrophils was studied using the in vitro model. It was found that after exposure to loratadine at a dose of 2.5 |jg / ml, the number of viable cells was comparable (p = 0.001) with that in an intact culture. Found a stimulating effect of second generation antihistamines (loratadine, desloratadine) in low doses on the activity of NADPH-dependent oxide reductase. The form of neutrophil death depended on the type and dose of the drug; apoptosis was predominantly observed after cell contact with loratadine and desloratadine. Against the background of an increase in the activity of ATPase and myeloperoxidase after contact with diphenhydramine and clemastine (2.5 jg / ml), the largest number of neutrophils producing reactive oxygen species was revealed. Under the influence of desloratodine and clemastine, exocytosis of cationic proteins into the extracellular space and the lowest production of cytokines after contact with the latter were established. Thus, exposure to Hl-antihistamines, active both extra- and intracellular (diphenhydramine, loratadine), probably disrupted the metabolism of neutrophils, which led to an increase in their killer potential. Clemastine, acting mainly extracellularly, minimized the toxic effects of extracellular radicals, without affecting the production of intracellular oxidants involved in the regulation of neutrophil functions.

2D- and 3D-cultures of human trabecular meshwork cells: A preliminary assessment of an in vitro model for glaucoma study.

A physiologically relevant in vitro human-based model could be the ‘gold standard’ to clarify the pathological steps involved in glaucoma onset. In this regard, human 3D cultures may represent an excellent starting point to achieve this goal. Indeed, the 3D matrix allows to re-create the in vivo-like tissue architecture, maintaining its functionality and cellular behaviour, compared to the 2D model. Thus, we propose a comparison between the 2D and 3D in vitro models of human trabecular meshwork cells in terms of cellular responses after chronic stress exposure. Our results showed that 3D-cells are more sensitive to intracellular reactive oxidative specie production induced by hydrogen peroxide treatment, compared to 2D cultures. Additionally, in 3D cultures a more accurate regulation of the apoptosis trigger and cell adaptation mechanisms was detected than in 2D models. In line with these findings, the 3D-HTMC model shows the ability to better mimic the in vivo cell behaviour in adaptive responses to chronic oxidative stress than 2D.

Attenuation of Fe(III)-reducing bacteria during table fluctuation of groundwater containing Fe2+

Groundwater table fluctuation during natural and anthropogenic processes can facilitate the interaction between oxygen (O2) from the unsaturated zone and ferrous iron (Fe2+) from the saturated zone. In light of previous findings that Fe(III)-reducing bacteria can be killed by the reactive oxidants produced from Fe2+ oxidation under static oxic conditions, we hypothesize that Fe(III)-reducing bacteria will be attenuated during groundwater table fluctuations. To test this hypothesis, this study explored the variations of cell numbers of Shewanella oneidensis strain MR-1 (MR-1), a typical strain of Fe(III)-reducing bacteria, together with dissolved oxygen (DO) and Fe2+, at different points during controlled groundwater table fluctuations in a sand column. The results showed that, during the rise of the water table, O2 in the pore air was entrapped by the deoxygenated groundwater, and Fe2+ in the groundwater was oxidized by the entrapped O2. In this process, 1.40–2.42 orders of magnitude of viable MR-1 cells were killed at different points in the column. Further investigation proposed that the death of MR-1 is caused by the production of intracellular reactive oxidants, such as O2•− and OH•, from the oxidation of adsorbed/absorbed Fe2+ instead of by bulk reactive oxidants, such as OH• and Fe(IV), produced from the oxidation of aqueous Fe2+. The findings here provide new insights for Fe biogeochemical cycling in the redox-dynamic zone.

Interactions between Aspergillus fumigatus and Pulmonary Bacteria: Current State of the Field, New Data, and Future Perspective.

Aspergillus fumigatus and Pseudomonas aeruginosa are central fungal and bacterial members of the pulmonary microbiota. The interactions between A. fumigatus and P. aeruginosa have only just begun to be explored. A balance between inhibitory and stimulatory effects on fungal growth was observed in mixed A. fumigatus–P. aeruginosa cultures. Negative interactions have been seen for homoserine-lactones, pyoverdine and pyochelin resulting from iron starvation and intracellular inhibitory reactive oxidant production. In contrast, several types of positive interactions were recognized. Dirhamnolipids resulted in the production of a thick fungal cell wall, allowing the fungus to resist stress. Phenazines and pyochelin favor iron uptake for the fungus. A. fumigatus is able to use bacterial volatiles to promote its growth. The immune response is also differentially regulated by co-infections.

Characterization of Purified Red Cabbage Anthocyanins: Improvement in HPLC Separation and Protective Effect against H₂O₂-Induced Oxidative Stress in HepG2 Cells.

In this study, the chemical profiles and antioxidant activities of red cabbage anthocyanin (RCA)-enriched extract are evaluated. The effects of column temperature on the HPLC resolution of the RCAs are studied. The HPLC resolutions became better as the column temperature increased from 20 °C–45 °C. An optimized HPLC condition was achieved at 45 °C and used for the quantification and qualification of the RCAs. The anthocyanins in the enriched powder are all derivatives of cyanidin (268 ± 2 μg/mg), mainly with 19% nonacylated, 51% monoacylated, and 31% diacylated structures with ferulic, sinapic, p-coumaric, and caffeic acids characterized by HPLC-MS. The RCA extracts markedly reduced intracellular oxidative stress production by H2O2 on HepG2 cells and consequently ameliorated cell apoptosis and improved viability. The analytical method and cellular antioxidant activity demonstration of the RCAs will greatly facilitate their functional applications.

Increased intracellular and extracellular oxidant production in phagocytes of rheumatic patients treated with biological therapy - whole blood quantification.

Infectious complications, resulting from reduced activity of immune cells, are the most severe and common adverse effects of biological therapy. This study analyzed the effect of biological therapy on blood phagocytes, focusing on the formation of reactive oxygen species (ROS), an important factor in the defence against invading pathogens. Intra- and extracellular ROS production were recorded separately, on the basis of luminol and isoluminol chemiluminescence in patients treated with antibodies against tumor necrosis factor-α or against interleukin-6 receptor. In comparison to healthy donors or to rheumatic patients treated with classical immunosuppressive drugs, biological therapy increased ROS formation in both compartments. This indicates that the anti-microbial activity of blood phagocytes was not reduced by TNFα- or IL-6-neutralizing therapy, at least in terms of ROS.The method presented does not require blood fractionation, which could modify activity of phagocytes and cause loss of some subpopulations of these cells. The technique is simple, requires microliter volumes of blood and is thus well applicable to clinical studies.

청아지황탕(靑蛾地黃湯)의 RAW264.7 Cell에서 항산화 및 항염증 효능 연구

Objectives This study was designed to investigate whether the Cheongajihwang-Tang (CT) has an inhibitory effect association with oxidation or inflammation in RAW264.7 cells. Methods Cytotoxic activity of CT extract on RAW264.7 cells was evaluated by using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) solution. Nitric oxide production was measured using Griess reagent system. The total phenolic contents and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity was measured to evaluate the anti-oxidative effects of CT. Dichlorofluorescin diacetate (DCFH-DA) has been used as a substrate for measuring intracellular oxidant production. Results Cheongajihwang-Tang does not impair the cell viability in tested concentration. CT showed anti-oxidative effects in vitro by decreasing electron donating ability, and also showed anti-inflammatory effects suppressing NO and ROS expression in LPS induced RAW264.7 activation. CT inhibited the generation of intracellular ROS production as dose dependant manner. Conclusions CT has anti-oxidative effects and anti-inflammatory activities. These results indicate that CT extract has an anti-inflammatory activities via anti-oxidative effects.

Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury.

Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

Rutin upregulates neurotrophic factors resulting in attenuation of ethanol-induced oxidative stress in HT22 hippocampal neuronal cells.

Alcoholism, which refers to the excessive consumption of alcohol, has deleterious effects on personal and social health worldwide. Oxidative stress evoked by ethanol plays an important role in the pathogenesis of neurodegenerative diseases. Rutin is a bioflavonoid that has been demonstrated to scavenge superoxide radicals. However, the effects of rutin on neuronal toxicity following ethanol-induced oxidative stress have not previously been investigated. Thus we investigated the antioxidant effect of rutin in hippocampal neuronal cells (HT22 cells) exposed to ethanol. We found that rutin pretreatment prevented the ethanol-induced decrease in protein level expression of nerve growth factor, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in HT22 cells. Cell viability as analyzed by the MTT method revealed a significant increase in cell viability in the rutin-treated group compared with the ethanol-only treated group. Antioxidant effect of rutin was confirmed to be due to reduction of intracellular reactive oxidative species production in ethanol-treated HT22 cells. Moreover, rutin significantly increased the level of the antioxidant glutathione, and the activities of the antioxidant enzymes superoxide dismutase and catalase. These findings indicate that rutin has potential as a therapeutic agent to treat alcohol-related neurodegenerative disorders.

β-Glucan induces reactive oxygen species production in human neutrophils to improve the killing of Candida albicans and Candida glabrata isolates from vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is among the most prevalent vaginal diseases. Candida albicans is still the most prevalent species associated with this pathology, however, the prevalence of other Candida species, such as C. glabrata, is increasing. The pathogenesis of these infections has been intensely studied, nevertheless, no consensus has been reached on the pathogenicity of VVC. In addition, inappropriate treatment or the presence of resistant strains can lead to RVVC (vulvovaginal candidiasis recurrent). Immunomodulation therapy studies have become increasingly promising, including with the β-glucans. Thus, in the present study, we evaluated microbicidal activity, phagocytosis, intracellular oxidant species production, oxygen consumption, myeloperoxidase (MPO) activity, and the release of tumor necrosis factor α (TNF-α), interleukin-8 (IL-8), IL-1β, and IL-1Ra in neutrophils previously treated or not with β-glucan. In all of the assays, human neutrophils were challenged with C. albicans and C. glabrata isolated from vulvovaginal candidiasis. β-glucan significantly increased oxidant species production, suggesting that β-glucan may be an efficient immunomodulator that triggers an increase in the microbicidal response of neutrophils for both of the species isolated from vulvovaginal candidiasis. The effects of β-glucan appeared to be mainly related to the activation of reactive oxygen species and modulation of cytokine release.

Sodium Ferulate Inhibits Neointimal Hyperplasia in Rat Balloon Injury Model

Background/AimNeointimal formation after vessel injury is a complex process involving multiple cellular and molecular processes. Inhibition of intimal hyperplasia plays an important role in preventing proliferative vascular diseases, such as restenosis. In this study, we intended to identify whether sodium ferulate could inhibit neointimal formation and further explore potential mechanisms involved.MethodsCultured vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta were pre-treated with 200 µmol/L sodium ferulate for 1 hour and then stimulated with 1 µmol/L angiotensin II (Ang II) for 1 hour or 10% serum for 48 hours. Male Sprague-Dawley rats subjected to balloon catheter insertion were administrated with 200 mg/kg sodium ferulate (or saline) for 7 days before sacrificed.ResultsIn presence of sodium ferulate, VSMCs exhibited decreased proliferation and migration, suppressed intracellular reactive oxidative species production and NADPH oxidase activity, increased SOD activation and down-regulated p38 phosphorylation compared to Ang II-stimulated alone. Meanwhile, VSMCs treated with sodium ferulate showed significantly increased protein expression of smooth muscle α-actin and smooth muscle myosin heavy chain protein. The components of Notch pathway, including nuclear Notch-1 protein, Jagged-1, Hey-1 and Hey-2 mRNA, as well as total β-catenin protein and Cyclin D1 mRNA of Wnt signaling, were all significantly decreased by sodium ferulate in cells under serum stimulation. The levels of serum 8-iso-PGF2α and arterial collagen formation in vessel wall were decreased, while the expression of contractile markers was increased in sodium ferulate treated rats. A decline of neointimal area, as well as lower ratio of intimal to medial area was observed in sodium ferulate group.ConclusionSodium ferulate attenuated neointimal hyperplasia through suppressing oxidative stress and phenotypic switching of VSMCs.

Effects of 47C allele (rs4880) of the SOD2 gene in the production of intracellular reactive species in peripheral blood mononuclear cells with and without lipopolysaccharides induction

Challenging of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharides (LPS) has been shown to activate monocytes and macrophages, leading to the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Manganese superoxide dismutase (MnSOD) is an important enzyme that may play a central role in the response to oxidative stress. 47C> T SNP of the SOD2 gene, the -9Val MnSOD is less efficient than the -9Ala version. We have previously characterized the cellular redox status of human PBMCs expressing either -9Ala (CC) or -9Val (TT) SOD2 and analyzed the responses of these cells to oxidative stress induced by LPS. Due to the observed alterations in the activities of these antioxidant enzymes, we decided to investigate their immunocontent and analyze the production of intracellular oxidants, as well as any resulting DNA damage. PBMCs were isolated from the blood of 30 healthy human volunteers (15 volunteers per allele). We then analyzed levels of nitrite, DNA damage by comet assay, TNF-α, carboxymethyl lysine and nitrotyrosine and assessed production of intracellular reactive species by the DCFH-DA-based assay and western blots were used to analyze protein levels. Our results show that there occurs an increase in nitric oxide production in both allele groups after challenge with LPS. A significant increase in DNA damage was observed in PBMCs after an 8-h LPS challenge. Cells expressing the SOD2 47C allele quickly adapt to a more intense metabolism by upregulating cellular detoxification mechanisms. However, when these cells are stressed over a long period, they accumulate a large quantity of toxic metabolic byproducts.

Inhibition of Oxidative Stress by Low-Molecular-Weight Polysaccharides with Various Functional Groups in Skin Fibroblasts

The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS’ functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent.

LYCOPENE PROTECTS CARDIOMYOCYTES AGAINST ISCHAEMIA/REPERFUSION-INJURY BY PREVENTING APOPTOSIS

ObjectivesReactive oxygen species (ROS)-mediated calpain activation has shown to play an important role in cardiomyocyte apoptosis. Lycopene is a natural antioxidant carotenoid that has been shown to have protective properties...

Prolonged Fasting Increases Nrf2 Nuclear Accumulation and DNA Binding Ability in Postweaned Northern Elephant Seals

Northern elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting and weaning. Prolonged fasting in elephant seals promotes insulin resistance, activates the renin‐angiotensin system and increases NADPH oxidase activity and protein expression without increasing oxidative damage or inflammation. Prolonged fasting also stimulates the antioxidant system of the elephant seal likely resulting in the prevention of oxidative damage. The redox‐senstive transcription factor Nrf2 is the main regulator of the adaptive response to oxidative stress. Nrf2 translocates into the nucleus and increases the transcription of antioxidant genes in response to intracellular oxidant production. To test the hypothesis that Nrf2 is activated in response to prolonged fasting in elephant seals, angiotensin II (Ang II) and TGF‐β circulating concentrations, along with NADPH oxidase 4 (Nox4) mRNA expression and Nrf2 nuclear content and DNA binding ability, were measured in blood and muscle samples collected from seals fasting for 1, 3, 5 and 7 weeks. Ang II and TGF‐β increased gradually through the fasting and where 40‐fold (Ang II) and 2‐fold (TGF‐β) higher at wk 7 than at wk 1. Nox4 was 5‐fold higher at wk 7 than at wk 1 while Nrf2 nuclear content and DNA binding ability were 2‐fold higher. Results show that prolonged fasting activates the adaptive response to oxidative stress in elephant seals and suggest that Ang II and TGF‐β stimulate Nox4, which may potentially mediate a hormetic protective response in fasting seals.

Mitochondria-Derived Reactive Intermediate Species Mediate Asbestos-Induced Genotoxicity and Oxidative Stress–Responsive Signaling Pathways

Background: The incidence of asbestos-induced human cancers is increasing worldwide, and considerable evidence suggests that reactive oxygen species (ROS) are important mediators of these diseases. Our previous studies suggested that mitochondria might be involved in the initiation of oxidative stress in asbestos-exposed mammalian cells.Objective: We investigated whether mitochondria are a potential cytoplasmic target of asbestos using a mitochondrial DNA–depleted (ρ0) human small airway epithelial (SAE) cell model: ρ0 SAE cells lack the capacity to produce mitochondrial ROS.Methods: We examined nuclear DNA damage, micronuclei (MN), intracellular ROS production, and the expression of inflammation-related nuclear genes in both parental and ρ0 SAE cells in response to asbestos treatment.Results: Asbestos induced a dose-dependent increase in nuclear DNA oxidative damage and MN in SAE cells. Furthermore, there was a significant increase in intracellular oxidant production and activation of genes involved in nuclear factor κB and proinflammatory signaling pathways in SAE cells. In contrast, the effects of asbestos were minimal in ρ0 SAE cells.Conclusions: Mitochondria are a major cytoplasmic target of asbestos. Asbestos may initiate mitochondria-associated ROS, which mediate asbestos-induced nuclear mutagenic events and inflammatory signaling pathways in exposed cells. These data provide new insights into the molecular mechanisms of asbestos-induced genotoxicity.

Anabolic Androgenic Steroids Abuse and Liver Toxicity

In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.