Macrophages play important roles in immunity and other physiological processes. They are also target cells of various toxic agents, including oxidants and electrophiles. However, little is known regarding the molecular regulation and chemical inducibility of a spectrum of endogenous antioxidants and phase 2 enzymes in normal macrophages. Understanding the molecular ...

Hystidyl-proline [cyclo(His-Pro)] is an endogenous cyclic dipeptide produced by the cleavage of thyrotropin releasing hormone. Previous studies have shown that cyclo(His-Pro) protects against oxidative stress, although the underlying mechanism has remained elusive. Here, we addressed this issue and found that cyclo(His-Pro) triggered nuclear accumulation of NF-E2-related factor-2 (Nrf2), a transcription ...

The hepatocyte growth factor and its receptor c-Met direct a pleiotropic signal transduction pathway that controls cell survival. We previously demonstrated that mice lacking c-Met (Met-KO) in hepatocytes were hypersensitive to Fas-induced liver injury. In this study, we used primary hepatocytes isolated from Met-KO and control (Cre-Ctrl) mice to address ...

Retinol (vitamin A) and other retinoids have been suggested to exert an important antioxidant function in biological systems, besides their more established role as regulators of cell growth and differentiation. On the other hand, many authors have recently observed pro-oxidant activities of vitamin A and other retinoids in vitro and ...

Selenium (Se) is an essential micronutrient as well as a toxic trace element in animal and human nutrition. The effects of Se in the immune system and some diseases are well documented. The objective of the present study was to examine the role of Se in reducing the hypoxia induced ...

The extracellular gamma-glutamyltransferase-mediated metabolism of glutathione has been implicated in prooxidant events which may have impact on cellular functions including drug resistance. This study was performed in two GGT-transfected melanoma clones to explore the hypothesis that GGT expression in tumour cells is implicated in modulation of cell behaviour under stress ...

Cerebellum is a vital organ responsible for the motor coordination and recently it has been reported to be involved in cognitive function. Reactive oxygen species are implicated in neurodegeneration and cognitive disorders because of higher vulnerability of neuronal tissues. Therefore, the present study aimed at investigating the role of melatonin ...

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of diabetic complications. Although some clinical evidences suggest the use of pyridoxal-5'-phosphate (PLP) in diabetes with nephropathy, the exact mechanism of PLP has not been fully understood. In the present study, the effect of PLP on 2-deoxy-D-ribose (dRib)-induced oxidative damages ...

FaO rat hepatoma cells show increased levels of the epidermal growth factor receptor (EGFR) ligands, when compared with adult normal hepatocytes, and higher activity of the TNF-alpha converting enzyme (TACE/ADAM17), which is required for EGFR ligand proteolysis and activation. In this work we have analysed the consequences of inhibiting the ...

Patulin is a mold toxin secreted mainly by fungi of the Penicillium species. Exposure generally results from consumption of moldy fruits and fruit products. Since recent studies identified mold exposure as a risk factor for allergic diseases, we examined the effects of patulin on human peripheral blood mononuclear cells (PBMC) ...

In order to establish causal or protective treatments for Parkinson's disease (PD), it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Paraquat (PQ) is a pesticide used as xenobiotic compound to model PD. However, the mechanism(s) of PQ-induced cell ...

Organophosphorus insecticide poisoning is widely investigated, and a growing number of evidence indicates its effects to cause ocular lesions, but the mechanisms of its ocular effects are not well elucidated. Here, effects of organophosphorus insecticide chlorpyrifos on mouse retina in vivo and protection of combination of vitamins C and E ...

Depletion of glutathione (GSH) by buthionine sulfoximine (BSO) has been reported to be toxic against some cancer cells and to sensitize many tumours including neuroblastoma (NB) to anticancer drugs. The balance between the production rate of reactive oxygen species (ROS) and the function of GSH affects the intracellular reduction-oxidation status, ...

The perturbation of the pro-oxidant/antioxidant balance can lead to increased oxidative damage, especially when the first line of antioxidant defense weakens with age. Chronic changes in the composition of factors present in aqueous or vitreous humor may induce alterations both in trabecular cells and in cells of the optic nerve ...

Mechlorethamine (HN2) and 2-chloroethylethyl sulfide (CEES) are mustard vesicants. Butylated hydroxyanisole (BHA) is a phenolic antioxidant. In the present work, the ability of BHA to reduce the toxicity of HN2 and CEES was investigated using A-431 skin cells. HN2 toxicity was found to be dependent, at least in part, on ...

The potential for carotenoids to modulate chronic diseases related to smoke is currently under investigation and renewed interest has been placed on achieving a better understanding of the mechanism(s) of action of carotenoids in smoke-exposed biological systems. Available data currently show that, while carotenoids alone are not harmful, their interaction ...

Peroxiredoxins participate in the antioxidant response by reducing H(2)O(2), organic peroxides and peroxynitrite. Peroxiredoxins have a conserved NH(2)-terminal cysteine residue that is oxidized to sulfenic acid during catalysis of peroxide reduction. In eukaryotes, the sulfenic acid can be further oxidized to a sulfinic acid. Resulting inactivation of peroxiredoxins favors H(2)O(2) ...

A high concentration of glucose has been implicated as a causal factor in initiation and progression of diabetic complications, and there is evidence to suggest that hyperglycemia increases the production of free radicals and oxidative stress. Therefore, compounds that scavenge reactive oxygen species may confer regulatory effects on high glucose-induced ...

This article discusses the current understanding of the role of free radicals and antioxidants in inflammatory processes and in ischemia reperfusion injury. It begins by describing the manifestations of acute inflammation and outlining the cellular events that occur during inflammation. It then describes the biochemical mediators of inflammation with special ...

BACKGROUND: Tong-Xin-Luo (TXL) - a mixture of herbal extracts, has been used in Chinese medicine with established therapeutic efficacy in patients with coronary artery disease. METHODS: We investigated the protective role of TXL extracts on endothelial cells injured by a known risk factor - palmitic acid (PA), which is elevated ...

This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well ...

Glyoxalases (Glo1 and Glo2) are involved in the glycolytic pathway by detoxifying the reactive methylglyoxal (MGO) into D-lactate in a two-step reaction using glutathione (GSH) as cofactor. Inhibitors of glyoxalases are considered as anti-inflammatory and anti-carcinogenic agents. The recent finding that various polyphenols modulate Glo1 activity has prompted us to ...

INTRODUCTION: 4-Hydroxynonenal (HNE) is one of the most abundant and reactive aldehydes of lipid peroxidation products and exerts various effects on intracellular and extracellular signalling cascades. We have previously shown that HNE at low concentrations could be considered as an important mediator of catabolic and inflammatory processes in osteoarthritis (OA). ...

Paracoccidioides brasiliensis is a dimorphic fungus that infects humans and establishes infection in the yeast form. We are interested in the mechanisms this fungus uses to evade the human immune system, and in its survival strategies within infected host cells. Reactive oxygen species play an important role in host defence, ...

Over the last century, our understanding of selenium has progressed considerably and we have come to recognize it as an essential component or cofactor of enzymes throughout metabolism, such as glutathione peroxidase (GPx), thioredoxine reductase and iodine deiodinase. GPx acts against hydrogen peroxide and lipid peroxidation and is an important ...

AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-II enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment. METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-gamma, interleukin-1 beta ...

Phyllanthus urinaria Linnea (Euphorbiaceae), is a traditional anti-hepatitis herb used in Taiwan. In continuation of our search for potent natural anti-inflammatory agents, from the ethanolic extract of this plant, nine compounds including phyllanthin (1), phyltetralin (2), trimethyl-3,4-dehydrochebulate (3), methylgallate (4), and rhamnocitrin (5), methyl brevifolincarboxylate (6), beta-sitosterol-3-O-beta-d-glucopyranoside (7), quercitrin (8), ...

Cellular and tissue injury associated with reactive oxygen species (ROS) has been reported in many kinds of disorders. While the antioxidant enzymes play critical roles in inhibiting the ROS-mediated injury, glutathione peroxidase (GPx) is scavenging hydroperoxides including H(2)O(2). We previously reported that Shengmai-san (SMS), a traditional Chinese medicine, prevented ischemia/reperfusion ...

Supplementation with both cystine and glutamic acid increases the synthesis of glutathione (GSH), which has a marked effect on immune cell function, as compared with supplementation with either amino acid alone in human macrophages in vitro. As dietary glutamic acid is metabolized during intestinal transport, oral administration of L-theanine (gamma-glutamylethylamide), ...

A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. This condition occurs ...

A mononuclear 1:1 copper complex of curcumin had been found to be superior to curcumin in its anti-oxidant properties. This paper describes the radio-protective effects of the complex in splenic lymphocytes from swiss mice. The complex was found to be very effective in protecting the cells against radiation-induced suppression of ...

A series of genistein derivatives, prepared by alkylation and difluoromethylation, were tested for their inhibitory effects on the hydrogen peroxide induced impairment in human umbilical vein endothelial (HUVE-12) cells in vitro. The HUVE-12 cells were pretreated with either the vehicle solvent (DMSO), genistein, or different amounts of the genistein derivatives ...

BACKGROUND: Macrolide antibiotics have anti-inflammatory effects which are utilized for the treatment of chronic inflammatory airway diseases. Recently, their anti-inflammatory effects have been proposed to be beneficial in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: Since the molecular mechanisms of anti-inflammatory effects are associated with inhibition of activator protein ...

The aim of the present work was to characterize the molecular basis of oxidative-induced death, a process that has been implicated in eye diseases like glaucoma, in RGC-5 cells, an immortalized retinal ganglion cell (RGC) line. Oxidative stress was induced by treatment of RGC-5 cells with hydrogen peroxide and compared ...

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRP1) function. The doxorubicin-resistant MRP1-overexpressing human SCLC cell line GLC(4)-Adr was highly sensitive for indomethacin compared with the parental doxorubicin-sensitive line GLC(4). The ...

Reduced glutathione (L-gamma-glutamyl-L-cysteinyl-glycine, GSH) is the prevalent low-molecular-weight thiol in mammalian cells. It is formed in a two-step enzymatic process including, first, the formation of gamma-glutamylcysteine from glutamate and cysteine, by the activity of the gamma-glutamylcysteine synthetase; and second, the formation of GSH by the activity of GSH synthetase which ...

Although polysaccharide is believed to play an important role in the medicinal effect of Dendrobium chrysotoxum Lindl (DCL), its role as an antioxidant and in anti-hyperglycemic induction was not reported. In this study, polysaccharide with molecular weight of approximately 150 kDa, herein named DCLP, was isolated from the stem of ...

Previously, we showed that cellular glutathione/glutathione disulfide (GSH/GSSG) play an important role in apoptotic signaling, and early studies linked mitochondrial GSH (mtGSH) loss to enhanced cytotoxicity. The current study focuses on the contribution of mitochondrial GSH transport and mitochondrial GSH/GSSG status to apoptosis initiation in a nontransformed colonic epithelial cell ...

Antimycin A (AMA) inhibits succinate oxidase and NADH oxidase, and also inhibits mitochondrial electron transport between cytochromes b and c. We investigated the involvement of ROS and GSH in AMA-induced HeLa cell death. AMA increased the intracellular H(2)O(2) and O(2)(*-) levels and reduced the intracellular GSH content. ROS scavengers (Tempol, ...

A growing body of evidence suggests that many of the effects of vascular dysfunction on cardiovascular diseases are mediated by the products of nonenzymatic reactions, such as the peroxidative degradation of polyunsaturated fatty acids (ie, lipid peroxidation). These degradation products are electrophilic reactive compounds and are thought to have a ...

There is increasing evidence to suggest that reactive oxygen species, including a variety of lipid oxidation products and other physiologically existing oxidative stimuli, can induce an adaptive response and enhance cell tolerance. In the present study, by using cultured cortical neurons, we investigated the effect of electrophilic lipids, such as ...

Changes in the intracellular redox environment of cells have been reported to be critical for the activation of apoptotic enzymes and the progression of programmed cell death. Glutathione (GSH) depletion is an early hallmark observed in apoptosis, and we have demonstrated that GSH efflux during death receptor-mediated apoptosis occurs via ...

BACKGROUND: Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent ...

Reactive oxygen and nitrogen species produced by metabolism and immune defenses can cause extensive damage to biomolecules. To counteract this damage, organisms rely on exogenous and endogenous antioxidants, although their relative importance in maintaining redox balance is unclear. We supplemented captive greenfinches with dietary antioxidants--carotenoids and vitamin E--and injected them ...

The antidiabetic effect of metformin is mediated by activation of AMP-activated kinase (AMPK). This study investigated whether metformin at a high pharmacologic concentration alters the levels of cellular GSH in H4IIE hepatocytes and if so, whether the agent affects cell viability under GSH-deficient conditions. Treatment of cells with either metformin ...

OBJECTIVE: Enhanced lipid peroxidation is well established in traumatic brain injury. However, its molecular targets, identity of peroxidized phospholipid species, and their signaling role have not been deciphered. METHODS: Using controlled cortical impact as a model of traumatic brain injury, we employed a newly developed oxidative lipidomics approach to qualitatively ...

Several hypotheses regarding the mechanism underlying amphetamine-induced neurotoxicity have been proposed. One of them is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of dopamine (DA). The formation of DA-related reactive oxygen species (ROS) such as superoxide and hydroxyl radicals appears to play an ...

Piper longum Linn. and Piper nigrum Linn. are conventionally used as immuno-enhancers in Indian system of traditional medicine. The underlying mechanism remains unknown. The present study was therefore, undertaken to delineate the role of piperine (major alkaloid) in cadmium (Cd) induced immuno-compromised murine splenocytes. The various biological determinants such as ...

(1) Morroniside belongs to an extensive group of natural iridorid glycosides. In the present study, using human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on H(2)O(2)-mediated cytoxicity. (2) Incubation of cells ...

4-Hydroxy-2-nonenal (HNE), the aldehydic product of lipid peroxidation, is associated with multiple immune dysfunctions, such as HIV and hepatitis C virus infection. HNE-induced immunosuppression could be due to a decrease in CD4+ T lymphocyte activation or proliferation. Glutathione (GSH) is the most abundant endogenous antioxidant in cells, and an adduct ...