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A natural compound contained in olive oil, 3,4-dihydroxyphenylethanol (DOPE), is also known as an endogenous metabolite of dopamine. The role of DOPE in oxidative stress-induced cell damage was investigated using differentiated PC12 cells. Superoxide (O 2 − ) and H 2 O 2 induced a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability denoted by MTT assay. While O 2 − -induced cell damage was not affected by DOPE, pretreatment of the cells with DOPE dose-dependently prevented the leakage of LDH induced by H 2 O 2 . In these cells, augmented activity of catalase was demonstrated, while the levels of glutathione and glutathione peroxidase activity remained unchanged. The effect of DOPE was abolished when an inhibitor of catalase 3-amino-l, 2,4-triazole, was included in the medium. DOPE also protected against cell damage induced by H 2 O 2 , and Fe 2+ . In the hydroxyl radical ( OH) assay using p -nitroso- N , N -dimethylaniline (PNDA), oxidation of PNDA by OH generated by the Fenton reaction was significantly attenuated in the presence of DOPE. By an electron spin resonance spin trapping study that represents the direct activity of DOPE to scavenge OH, however, limited scavenging activity was demonstrated for DOPE. Taken together, DOPE may act as a unique cytoprotective compound in nerve tissue subjected to oxidative stress.

Aim Food additives and agricultural chemicals consumed in daily life can be endocrine-disrupting chemicals (EDCs) for humans. EDCs have been reported to influence our genital function, learning ability and recognition. We have reported that the production of reactive oxygen species (ROS) precedes the decrease in sperm motility and/or numbers (FRR 2010), suggesting oxidative stress plays a key role. Therefore, we have studied the effects of a strong antioxidant, coenzyme Q 10 (CoQ10) on the rat sperm toxicity induced by diethylstilbestrol (DES), one of EDCs. Methods Drinking water containing DES (0.1 mg/L) ± CoQ10 (300 or 600 mg/kg/day; Kaneka Co.) were given to Wistar rats (13 weeks old) for 8 weeks. The numbers and the motility of sperm, and lipid peroxidation products in the testicle were measured. Result Reduced CoQ10 was absorbed and transferred to rat blood and liver, but only a little to the testicle. Administration of DES decreased the number of sperm in the cauda epididymidis, and motility functions (curve line speed, and the head amplitude). Supplementation of reduced CoQ10 did not rescue the decline of sperm numbers. However, both the curved line speed and the head amplitude of the sperm which are important functions of fertilization were improved significantly by reduced CoQ10. HNE (4-hydroxy-2-nonenal) modified proteins (28 and 53 kDa) in the testicle were increased significantly by DES administration. Reduced CoQ10 significantly decreased HNE-modified proteins. Conclusion Although the reduced CoQ10 supplementation to rats did not rescue the decline of total sperm numbers induced by DES administration, it significantly reduced oxidative stress in the testis and improved sperm function. These results suggested that the systemic absorption of reduced CoQ10 might inhibit oxidative stress of the testicle and dysfunction of the sperm.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.

It is increasingly apparent that oxidants can play an important role in mediating specific cell responses and expression of genes involved in degenerative pathophysiologic states, such as inflammation. In particular, oxidant-induced activation of the multisubunit nuclear transcription factor, NFkappaB, has been implicated in the transcriptional upregulation of inflammatory genes like endothelial cell adhesion glycoproteins. A second emerging concept is the recognition that the oxidant effects in cellular and molecular regulation may be mediated by oxidant-induced loss of cellular oxidation-reduction (redox) balance. This review will provide an overview of our current understanding of leukocyte-endothelial cell interactions derived from in vitro studies of endothelial cell monolayers exposed to anoxia/reoxygenation, with specific emphasis on the molecular determinants mediating this inflammatory process and the contribution of reoxygenation-induced cellular redox imbalance to the activation of NFkappaB and the expression of endothelial surface adhesion molecules.

Helicobacter pylori (H. pylori)-infection leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease, and gastric neoplasia. The key determinants of these outcomes are the severity and distribution of the H. pylori-induced inflammation. Antral-type gastritis is associated with excessive acid secretion and a high risk of duodenal ulcer. In contrast, gastritis that involves the acid-secreting corpus region leads to hypochlorhydria, progressive gastric atrophy, and an increased risk of gastric cancer. The key pathophysiological event in H. pylori infection is initiation and continuance of an inflammatory response. Bacteria or their products trigger this inflammatory process and the main mediators are cytokines. Identification of both host- and bacterial-factors that mediate is an intense area of interest in current researches. Recent data indicates that the cag pathogenicity island plays a crucial role in H. pylori-induced gastric inflammation via the activation of gene transcription. It has been demonstrated that oxidative and nitrosative stress associated with inflammation plays an important role in gastric carcinogenesis as a mediator of carcinogenic compound formation, DNA damage, and cell proliferation. Genetic information regulating such stress would be one of the host factors determining the outcome—particularly when the outcome is gastric cancer— of H. pylori infection, and the compound that attenuates such stress may be a candidate for use in chemo- prevention. This review highlights recent advances in understanding of the mechanisms underlying chronic inflamma- tion following infection with H. pylori. © 2002 Elsevier Science Inc.

Nitric oxide (NO) modulation of ischemia-reperfusion injury was investigated by measuring lipid peroxide and neutrophil accumulation in rat stomachs treated with N G -nitro- l -arginine ( l -NNA), a specific NO synthase inhibitor. Ischemia-reperfusion injury was induced in the rat stomach. Treatment with l -NNA for 3 days at a dose of 3 mg/kg/day significantly enhanced this injury. This enhancement was reversed by the simultaneous administration of l -arginine at a dose of 30 mg/kg/day. Both thiobarbituric acid (TBA)-reactive substances, an index of lipid peroxidation, and myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, were increased in the gastric mucosa after ischemia-reperfusion. l -NNA treatment enhanced these increases in TBA-reactive substances and MPO activity. The increase in the area of gastric erosions correlated closely with accumulation of TBA-reactive substances as well as the increase in MPO activity. Enhancement of ischemia-reperfusion injury by l -NNA treatment was inhibited by injection with anti-neutrophil antibody, anti-platelet activating factor (PAF) antagonist, and anti-leukotriene B 4 (LTB 4 ) receptor antagonist. In addition, the increase in TBA-reactive substances and MPO activity was decreased by these antibodies or antagonists. Enhancement of reperfusion-induced gastric mucosal injury associated with inhibition of NO synthesis may involve neutrophil infiltration and lipid peroxide accumulation in the gastric mucosa, mediated by PAF and LTB 4 .

Since the toxicity of diesel exhaust particles (DEP) after intratracheal injection, was suppressed by pretreatment with superoxide dismutase (SOD) modified with polyethylene glycol (Sagai et al. Free Rad. Biol. Med. 14: 37-47; 1993), the possibility that superoxide could be enzymatically and continuously generated from diesel exhaust particles (DEP), was examined. Nicotinamide-adenine dinucleotide phosphate, reduced (NADPH) oxidation was stimulated during interaction of a methanol extract of DEP with the Triton N-101 treated microsomal preparation of mouse lung whereas the cytosolic fraction was less active, suggesting that DEP contains substrates for NADPH-cytochrome P450 reductase (EC 1.6.2.4, P450 reductase) rather than DT-diaphorase. When purified P450 reductase was used as the enzyme source, the turnover value was enhanced approximately 260-fold. Quinones appeared to be served as substrate for P450 reductase because reaction was inhibited by addition of glutathione (GSH) to form those GSH adduct or pretreatment with NaBH4 to reduce those to the hydroxy compounds although a possibility of nitroarenes as the alternative substrates cannot be excluded. A methanol extract of DEP (37.5 micrograms) caused a significant formation of superoxide (3240 nmol/min/mg protein) in the presence of P450 reductase. Electron spin resonance (ESR) experiments revealed that hydroxyl radical was formed as well. The reactive species generated by DEP in the presence of P450 reductase caused DNA scission which was reduced in the presence of superoxide dismutase (SOD), catalase, or hydroxyl radical scavenging agents. Taken together, these results indicate that DEP components, probably quinoid or nitroaromatic structures, that appear to promote DNA damage through the redox cycling based generation of superoxide.

Objectives S-allyl cysteine (SAC) is the most abundant compound in aged garlic extracts (AGEs). AGE has been reported to ameliorate the oxidative damage implicated in a variety of diseases. However, the effects of SAC have not been established in liver cirrhosis. The aim of this study was to examine the survival and the effect of therapeutic administration of SAC in the established liver fibrosis by chronic carbon tetrachloride (CCl 4 ) administration in rats. Materials & Methods Male Wistar rats (4 weeks age) were used. Cirrhosis was induced by chronic CCl 4 (2 ml/kg, 25% in corn oil, twice a week) intraperitoneal administration. Four weeks after CCl 4 treatment, SAC or cysteine compounds (cysteine, N-acethyl cysteine) were given by mixed diets for 8 weeks (CCl 4 :total 12 weeks) or longer (survival rate). Results CCl 4 administration elevated plasma alanine aminotransferase, plasma lipid peroxidation, liver hydroxyproline, and liver transforming growth factor (TGF)-beta at 12 weeks. SAC markedly normalized these changes induced by CCl 4 than other cysteine compounds. Furthermore, SAC improved survival in a dose-dependent manner following consecutive CCl 4 administration. The inhibitory mechanisms may be associated with a decrease in the profibrogenic cytokine, TGF-beta as well as the antioxidative properties of SAC. Conclusion Therapeutic administration of SAC improved liver fibrosis developed by CCl 4 and survival rate. These findings suggest SAC is a beneficial candidate for therapeutic agents on the liver cirrhosis.