Superoxide anion is the first generated reactive oxygen species (ROS) after oxygen enters living cells. It was once considered to be highly deleterious to cell functions and aging. Therefore, antioxidants were suggested to prevent aging and degenerative diseases. However, superoxide signaling has been shown in many physiological responses such as transcriptional regulation, protein activation, bioenergy output, cell proliferation and apoptosis. The uncoupling proteins (UCPs) are a family of mitochondrial anion-carrier proteins located in the inner mitochondrial membrane and are considered to reduce the generation of superoxide anion through the mitochondrial mild uncoupling. UCPs are important in prevention of mitochondrial excessive generation of ROS, transfer of mitochondrial substrates, mitochondrial calcium uniport and regulation of thermogenesis. Superoxide anion and uncoupling proteins are linked to Alzheimer’s disease in mitochondria. Simultaneous disorders of superoxide and uncoupling proteins create the conditions for neuronal oxidative damages. On the one hand, sustained oxidative damage causes neuronal apoptosis and eventually, accumulated neuronal apoptosis, leading to exacerbations of Alzheimer’s disease. On the other hand, our study has shown that UCP2 and UCP4 have important impact on mitochondrial calcium concentration of nerve cells, suggesting that their abnormal expression may involve in the pathogenesis of Alzheimer’s disease.
Key molecular players that link inflammation to carcinogenesis are prostaglandins, cytokines, nuclear factor-κB (NF-κB), chemokines, angiogenic growth factors, and free radicals, all of which lead to increased mutations and altered functions of important enzymes and proteins, for example, activation of oncogenic products and/or inhibition of tumor suppressor proteins, in inflamed tissues, thus contributing to multi-stage carcinogenesis process. Interpreted reversely, the identification of the molecular mechanisms by which chronic inflammation increases cancer risk or optimal intervention of targeted drugs or agents during the inflammation-associated carcinogenic process could be a necessary basis for developing new strategy of cancer prevention at many sites. In this review, we discuss the possibilities for cancer prevention by controlling inflammation process in Helicobacter pylori (H. pylori)-associated inflamed stomach with Korea red ginseng. Korea red ginseng is a good example of a natural herb that has ubiquitous properties that are conductive to stop inflammatory carcinogenesis that is un wanted outcome of H. pylori infection, rendering rejuvenation of chronic atrophic gastritis.
Overintake of sucrose or fructose induces adiposity. Fructose undergoes a strong Maillard reaction, which worsens diabetic complications. To determine whether Eucalyptus globulus leaf extract (ELE) suppresses the postprandial elevation of serum fructose concentrations (SFCs) in the portal, cardiac, and peripheral blood after sucrose ingestion, we performed gas chromatography/mass spectrometry (GC/MS) and measured SFC without any interference by contaminating glucose in the samples. Fasting Wistar rats were orally administered water (control group) or ELE (ELE group) before sucrose ingestion. Blood was collected from the portal vein, heart, and tail. The increase in the SFCs in the portal and cardiac samples 30 min after sucrose ingestion was lower in the ELE group than in the control group. The coefficient of correlation between the SFCs in the portal and cardiac samples was 0.825. The peripheral SFC in the control group progressively increased and was 146 μmol/L at 60 min. This increase was significantly lower in the ELE group. In contrast, the serum glucose concentrations in the 2 groups were similar. ELE suppressed postprandial hyperfructosemia in the portal, cardiac, and peripheral circulations. ELE may counteract glycation caused by high blood fructose concentrations induced by the consumption of fructose-containing foods or drinks.
Diet-induced obesity in C57BL/6 mice triggers common features of human metabolic syndrome (MetS). The purpose is to assess the suitability of a diet-induced obesity model for investigating non-alcoholic fatty pancreatic disease (NAFPD), fatty liver and insulin resistance. Adult C57BL/6 mice were fed either high-fat chow (HFC, 60% fat) or standard chow (SC, 10% fat) during a 16-week period. We evaluated in both groups: hepatopancreatic injuries, pancreatic islets size, alpha and beta-cell immunodensities, intraperitoneal insulin tolerance test (IPITT) and oral glucose tolerance test (OGTT). The HFC mice displayed greater mass gain (p<0.0001) and total visceral fat pads (p<0.001). OGTT showed impairment of glucose clearance in HFC mice (p<0.0001). IPITT revealed insulin resistance in HFC mice (p<0.0001). The HFC mice showed larger pancreatic islet size and significantly greater alpha and beta-cell immunodensities than SC mice. Pancreas and liver from HFC were heavier and contained higher fat concentration. In conclusion, C57BL/6 mice fed a high-fat diet develop features of NAFPD. Insulin resistance and ectopic accumulation of hepatic fat are well known to occur in MetS. Additionally, the importance of fat accumulation in the pancreas has been recently highlighted. Therefore, this model could help to elucidate target organ alterations associated with metabolic syndrome.
Although photoprotective properties of skin melanin have been well documented, a few studies on the effect of melanin on reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation have been reported. To study the interaction of melanin with ROS, scavenging or quenching effect of melanin on O2•− and 1O2 was examined by electron spin resonance (ESR)-spin trapping methods and a spectrophotometric method, respectively. Melanin potently interacted with O2•− generated in a hypoxanthine (HPX)-xanthine oxidase (XOD) reaction, and with 1O2 generated from a peroxidase, H2O2, and halide system. In the HPX-XOD reaction, it was proved that melanin doses not interfere with the enzyme reaction. It is confirmed that one of the mechanisms by which melanin protects UV-induced skin damage is likely scavenging or quenching activity against ROS such as O2•− and 1O2.
The clinical features of patients reflux esophagitis without any symptoms have not been clearly demonstrated. This study evaluated the clinical features of patients with endoscopy-positive reflux esophagitis, who did not complain of symptoms, as detected by brief questioning by nursing staffs. Eight thousand and thirty-one patients not taking medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia and acid regurgitation by nursing staffs before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) patients were classified as positive for reflux esophagitis. The endoscope positive subjects who complain heartburn were 539/1199 (45.0%).The endoscope positive subjects who do not complain symptoms were 465 in 1199 positive reflux esophagitis (38.8%). We compared endoscopic positive subjects without any complain by brief question by nursing staffs to endoscopic positive subjects with heartburn. Male gender, no obesity, absence of hiatus hernia, and low-grade esophagitis were associated with endoscopy-positive patients who do not complain of symptoms. The results of this study indicated correct detection of clinical symptoms of reflux esophagitis might be not easy with brief questioning by nursing staffs before endoscopic examination.
Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-α levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-α after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-α after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-κB (NF-κB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-κB activation and subsequent induction of proinflammatory products such as NO and TNF-α, but not HSP induction.
Reduced coenzyme Q10 (CoQ10H2) is known as a potent antioxidant in biological systems. However, it is not yet known whether CoQ9H2 could act as an antioxidant in human cells. The aim of this study is to assess whether exogenously added CoQ9 can protect human liver cells against injuries induced by a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and a lipid-soluble radical initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). CoQ9-enriched cells were obtained by treatment of HepG2 cells with 10 μM CoQ9 liposomes for 24 h. CoQ9-enriched cells were exposed to 10 mM AAPH and 500 μM AMVN over 4 h and 24 h, respectively. The loss of viability after treatment with AAPH or AMVN was much less in CoQ9-enriched cells than in naive HepG2 cells. The decrease in glutathione and the increase in thiobarbituric acid-reactive substance after treatment with AAPH or AMVN were also suppressed in CoQ9-enriched cells. The incubation of CoQ9-enriched cells with AAPH or AMVN led to a decrease in cellular CoQ9H2 and reciprocal increase in cellular CoQ9 resulting from its antioxidant function. Taken together, it was demonstrated for the first time that exogenously added CoQ9 could prevent oxidative stress-mediated damage to human cells by virtue of its antioxidant activity.
Geranylgeranoic acid (GGA) is one of the most potent cancer-preventive acyclic retinoids. GGA has been shown to induce cell death in human hepatoma-derived HuH-7 cells. We have recently reported the natural occurrence of GGA and its related compounds in several medicinal herbs such as turmeric, basil, rosehip, cinnamon and others [Shidoji and Ogawa, J. Lipid Res., 45: 1092–1103, 2004]. In the present study, we performed oral administration of turmeric tablets to healthy volunteers in order to investigate bioavailability of natural GGA. By using liquid chromatography/mass spectrometry, authentic GGA was eluted at a retention time of around 18 min as a negative ion of m/z 303.4. With healthy volunteers, plasma GGA was detected prior to the tablet intake and its concentrations were increased at 2 h after its intake and maintained at higher level until 4 h, suggesting an efficient bioavailability of preformed GGA in the turmeric tablets through oral administration. These results indicated that GGA in the turmeric tablet was absorbed as an intact form from intestinal mucosa. The present study provides a clue to conduct a research for cancer preventive roles of GGA in a number of spices.
Helicobacter pylori (HP)-eradication therapy increases Runt domain transcription factor 3 (RUNX3) expression in the glandular epithelial cells in enlarged-fold gastritis. The aim of this study is to evaluate expression of the RUNX3 protein, the product of a gastric tumor suppression gene, and mutagenic oxidative stress in human gastric mucosal specimens obtained from patients with HP-induced enlarged-fold gastritis. Methods. RUNX3 expression was immunohistochemically scored and the degree of the mucosal oxidative stress was directly measured by the chemiluminescense (ChL) assay in the biopsy specimens. Results. RUNX3 expression was detected in the gastric epithelial cells. HP-eradication significantly increased RUNX3 expression in the glandular epithelium of the corpus, however, no change was observed in those of the antrum. A fourfold higher mucosal ChL value was observed in the corpus as compared with that in the antrum. HP-eradication significantly decreased the mucosal ChL values in both portions of the stomach to nearly undetectable levels. Conclusion. The glandular epithelium is exposed to a high level of carcinogenic oxidative stress and shows low levels of expression of the tumor suppressive molecule, RUNX3; however, this expression was restored after HP-eradication, suggesting the high risk of carcinogenesis associated with HP-induced enlarged-fold gastritis of the corpus.
Asbestos-induced mesothelioma is a challenging social problem in many countries, and oxidative stress via iron is closely associated with its carcinogenesis. Mesothelioma is thought to originate from the mesothelial cells that cover the somatic cavity such as pleural, pericardial and peritoneal cavities. They are single layered and so flat that it is extremely difficult to obtain pure mesothelial cells as control samples from experimental animals. Here we describe a novel method to collect mesothelial cells from animals by the use of simple equipments. Surface of the most organs including lung, spleen and liver are covered with a single layer of mesothelial cells. Scraping the surface of those organs with razor blades after snap-freeze in liquid nitrogen satisfactorily confers almost pure population of mesothelial cells. This simple method would be helpful for obtaining mesothelial control samples from animals to elucidate the molecular mechanisms of a variety of mesothelial pathology.
Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.