Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases.

Objective: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid.

Methods: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects.

6-hydroxydopamine increases hydroxyl free radical production and DNA damage in rat striatum.

Oxidative damage is considered to be an important factor of 6-hydroxydopamine (6-OHDA) toxicity. To address this issue, microdialysis probes were implanted into the striatum of Wistar rats and perfused with 6-OHDA. Salicylate was included in the perfusion fluid to measure 2,3-dihydroxybenzoic acid (2,3-DHBA) as a marker of hydroxyl radical formation using HPLC with electrochemical detection.

Hydrogen peroxide. Ubiquitous in cell culture and in vivo?

Hydrogen peroxide (H2O2) is widely regarded as a cytotoxic agent whose levels must be minimized by the action of antioxidant defence enzymes. In fact, H2O2 is poorly reactive in the absence of transition metal ions. Exposure of certain human tissues to H2O2 may be greater than is commonly supposed; levels of H2O2 in the human body may be controlled not only by catabolism but also by excretion, and H2O2 could play a role in the regulation of renal function and as an antibacterial agent in the urine.

Lipid peroxidation in the postnatal rat brain. Formation of 4-hydroxynonenal in the supraventricular corpus callosum of postnatal rats.

Lipid peroxidation is known to be associated with many neurodegenerative diseases and with traumatic brain injury, but its occurrence in the normal developing brain has not been reported. The present study was carried out using a specific antibody that recognises proteins modified by the end-product of lipid peroxide decomposition, 4-hydroxynonenal (HNE), to evaluate evaluate possible lipid peroxidation products in the brains of developing rats by immunocytochemistry and electron microscopy. Moderately dense labelling was observed in the supraventricular corpus callosum in the 7- and 8-day-old rats, whilst very dense labelling was observed in the same region, in the 9- and 10-day-old rats.

Vitamin C and genomic stability.

Vitamin C, a water-soluble glucose derivative, has considerable antioxidant activity in vitro, in part because of its ease of oxidation and because the semidehydroascorbate radical derived from it is of low reactivity. Vitamin C in vivo is an essential cofactor for a range of enzymes involved in diverse metabolic pathways, but much recent literature has focused on its antioxidant effects. Consumption of foods rich in Vitamin C (fruits and vegetables) is associated with decreased risk of cardiovascular disease, of many types of cancer and possibly of neurodegenerative disease, but the extent to which Vitamin C contributes to these effects is uncertain.

The in vitro cytotoxicity of ascorbate depends on the culture medium used to perform the assay and involves hydrogen peroxide.

Reports about the effects of ascorbate (vitamin C) on cultured cells are confusing and conflicting. Some authors show inhibition of cell death by ascorbate, whereas others demonstrate that ascorbate is cytotoxic. In this report, using three different cell types and two different culture media (Dulbecco's modified Eagle's medium and RPMI 1640), we show that the toxicity of ascorbate is due to ascorbate-mediated production of H2O2, to an extent that varies with the medium used to culture the cells.

The gastrointestinal tract: a major site of antioxidant action?

Diets rich in fruits and vegetables delay the onset of many age-related diseases, and contain a complex mixture of antioxidants (including ascorbate, carotenoids, vitamin E and other phenolics such as the flavonoids). However, diet also contains pro-oxidants, including iron, copper, H2O2, haem, lipid peroxides and aldehydes. Nitrite is frequently present in diet, leading to generation of reactive nitrogen species in the stomach.

Effect of the overexpression of wild-type or mutant alpha-synuclein on cell susceptibility to insult.

Mutations in alpha-synuclein (A30P and A53T) are involved in some cases of familial Parkinson's disease (FPD), but it is not known how they result in nigral cell death. We examined the effect of alpha-synuclein overexpression on the response of cells to various insults. Wild-type alpha-synuclein and alpha-synuclein mutations associated with FPD were overexpressed in NT-2/D1 and SK-N-MC cells.

Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis.

Patients with Down's syndrome (DS) show elevated levels of copper, zinc-containing superoxide dismutase (SOD1) and appear to have increased lipid peroxidation and oxidative damage to DNA as well as elevated glutathione peroxidase activity. Increasing SOD1 levels by gene transfection in NT-2 and SK-N-MC cell lines also led to a rise in glutathione peroxidase activity, but this was nevertheless accompanied by decreased proliferation rates, increased lipid peroxidation and protein carbonyls, and a trend to a rise in 8-hydroxyguanine and protein-bound 3-nitrotyrosine. Transfection of these cell lines with DNA encoding two mutant SOD1 enzymes (G37R and G85R) associated with familial amyotrophic lateral sclerosis (FALS), produced similar, but more severe changes, i.

A reevaluation of the peroxynitrite scavenging activity of some dietary phenolics.

Peroxynitrite is implicated in many diseases. Hence, there is considerable interest in potential therapeutic peroxynitrite scavengers. Diet-derived phenolics have been claimed to be powerful peroxynitrite scavengers.

Hydrogen peroxide in the human body.

Hydrogen peroxide (H(2)O(2)) is widely regarded as a cytotoxic agent whose levels must be minimized by the action of antioxidant defence enzymes. In fact, H(2)O(2) is poorly reactive in the absence of transition metal ions. Exposure of certain human tissues to H(2)O(2) may be greater than is commonly supposed: substantial amounts of H(2)O(2) can be present in beverages commonly drunk (especially instant coffee), in freshly voided human urine, and in exhaled air.

Why and how should we measure oxidative DNA damage in nutritional studies? How far have we come?

Free radicals and other reactive species are constantly generated in vivo and cause oxidative damage to DNA at a rate that is probably a significant contributor to the age-related development of cancer. Agents that decrease oxidative DNA damage should thus decrease the risk of cancer development. That is, oxidative DNA damage is a "biomarker" for identifying persons at risk (for dietary or genetic reasons, or both) of developing cancer and for suggesting how the diets of these persons could be modified to decrease that risk.

Potential problems of ascorbate and iron supplementation: pro-oxidant effect in vivo?

The comparison was undertaken between the effects of ascorbate versus ascorbate plus iron supplementation on DNA damage. Twenty healthy subjects with initial levels of plasma ascorbate of 67.2 +/- 23.

Haptoglobin reduces renal oxidative DNA and tissue damage during phenylhydrazine-induced hemolysis.

Background: Haptoglobin knockout (Hp-/-) mice are more sensitive to phenylhydrazine-induced hemolysis than Hp+/+ mice.

Methods: Hemolysis was induced in Hp-/- and Hp+/+ mice using phenylhydrazine. Relative renal tissue damage and function were then assessed.

Changes in glutathione in the hippocampus of rats injected with kainate: depletion in neurons and upregulation in glia.

The aim of the present study was to elucidate the distribution of glutathione immunoreactivity in the normal hippocampus and after kainate-induced neuronal injury. A specific antibody was used that recognizes both the reduced (GSH) and oxidized (GSSG) forms of glutathione. Immunoreactivity to glutathione was observed in neurons, but few immunolabeled glial cells were observed in the normal hippocampus.

No evidence for increased oxidative damage to lipids, proteins, or DNA in Huntington's disease.

It has been proposed that mitochondrial dysfunction and excitotoxic mechanisms lead to oxidative damage in the brain of Huntington;s disease patients. We sought evidence that increased oxidative damage occurs by examining postmortem brain material from patients who had died with clinically and pathologically diagnosed Huntington's disease. Oxidative damage was measured using methods that have already demonstrated the presence of increased oxidative damage in Parkinson's disease, Alzheimer's disease, and senile dementia of the Lewy body type.

Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat hippocampus: evidence that hydroxynonenal formation precedes neuronal cell death.

Decomposition of lipid peroxides gives rise to a wide range of aldehydes. 4-Hydroxyalkenals and in particular 4-hydroxynonenal (HNE) are often the most toxic products. Frequently, it is unclear at which stage in the tissue injury process HNE is formed, i.

Measurement of plasma F2-isoprostanes as an index of lipid peroxidation does not appear to be confounded by diet.

F2-isoprostanes (F2-IPs) are formed by the free radical-catalysed oxidation of arachidonic acid. The measurement of F2-IPs, especially 8-epi-PGF2alpha, is recognised as a reliable marker of lipid peroxidation and is currently used as a sensitive index of oxidative stress in vivo. The majority of 8-epi-PGF2alpha present in the circulation occurs in association with lipoproteins which are synthesised in the liver.

Artifacts in cell culture: rapid generation of hydrogen peroxide on addition of (-)-epigallocatechin, (-)-epigallocatechin gallate, (+)-catechin, and quercetin to commonly used cell culture media.

There is considerable current interest in the possible beneficial health effects of quercetin, catechins, epigallocatechins, epigallocatechin gallates, and related phenolic compounds found in teas, wines, and other plant products. As a result, many laboratories are studying the effects of these compounds on cells in culture. The present paper shows that addition of these compounds to commonly used cell culture media leads to generation of substantial amounts of hydrogen peroxide (H(2)O(2)).

Free radicals and antioxidants in the year 2000. A historical look to the future.

In the late 1950's free radicals and antioxidants were almost unheard of in the clinical and biological sciences but chemists had known about them for years in the context of radiation, polymer and combustion technology. Daniel Gilbert, Rebeca Gerschman and their colleagues related the toxic effects of elevated oxygen levels on aerobes to those of ionizing radiation, and proposed that oxygen toxicity is due to free radical formation, in a pioneering paper in 1956. Biochemistry owes much of its early expansion to the development and application of chromatographic and electrophoretic techniques, especially as applied to the study of proteins.

Free radicals and hearing. Cause, consequence, and criteria.

Reactive oxygen and nitrogen species, including free radicals, are produced in the human body in both health and disease. In health, they may arise as regulatory mechanisms, intercellular signaling species, or as bacteriocidal agents. Their production is normally controlled by the antioxidant defense mechanisms that include intracellular enzymes--for example, glutathione peroxidase and superoxide dismutase--and low molecular-mass compounds such as vitamin E or ascorbic acid.