Biofactors - Volume 28, issue 1

Authors: Ishikawa, Takeshi | Yoshida, Norimasa | Tokuda, Harukuni | Kokura, Satoshi | Nakabe, Nami | Kuchide, Masashi | Ichiishi, Eiichiro | Imaeda, Atsumune | Ichikawa, Hiroshi | Naito, Yuji | Okanoue, Takeshi | Yoshikawa, Toshikazu

Article Type: Research Article

Abstract: Helicobacter pylori (H. pylori) infection, the main cause of chronic gastritis, increases gastric cancer risk. The infection causes inflammatory cells to produce reactive oxygen metabolites that may damage DNA and promote carcinogenesis. However, its precise role in gastric carcinogenesis is as yet unknown. Recently we reported that H. pylori water extract (HPE) has an initiating activity on two-stage mouse skin carcinogenesis. In this study, we investigated the effects of anti-oxidants, ascorbic acid and a …combination of superoxide dismutase (CuZnSOD)and catalase, on two-stage mouse skin carcinogenesis. Ascorbic acid and CuZnSOD/catalase were given to mice during the period of HPE-initiation. Both the ascorbic acid and CuZnSOD/catalase treatment attenuated the incidence of tumor formation. The present results suggest that HPE induces tumor formation via reactive oxygen species (ROS) production. Show more

Keywords: H. pylori, carcinogenesis, reactive oxygen species, mouse skin carcinogenesis

Citation: BioFactors, vol. 28, no. 1, pp. 1-7, 2006

Authors: Sugimoto, Naohito | Yoshida, Norimasa | Nakamura, Yasunari | Ichikawa, Hiroshi | Naito, Yuji | Okanoue, Takeshi | Yoshikawa, Toshikazu

Article Type: Research Article

Abstract: We investigated the effect of vitamin E on gastric mucosal injury induced by Helicobacter pylori (H. pylori) infection. Male Mongolian gerbils were divided into 4 groups (normal group without H. pylori infection, vitamin E-deficient, -sufficient and -supplemented groups with H. pylori infection). Following oral inoculation with H. pylori (ATCC43504 2 × 10^{8} CFU), animals were fed diets α-tocopherol 2 mg/100 g diet in the normal and vitamin E-sufficient groups and …α-tocopherol 0.1 mg/100 g and 50 mg/100 g in the vitamin E-deficient and -supplemented groups, respectively, for 24 weeks. Chronic gastritis was detected in all gerbils inoculated H. pylori. Gastric ulcer was detected in 2 of 7 gerbils only in the vitamin E-deficient group. In the vitamin E-deficient group, myeloperoxidase activity and mouse keratinocyte derived chemokine (KC) in gastric mucosa was significantly higher than in the vitamin E supplemented group. Subsequently, in an in vitro study expression of CD11b/CD18 on neutrophils was enhanced by H. pylori water extract. This effect was suppressed in a dose dependent manner by the addition of α-tocopherol. These results suggest that vitamin E has a protective effect on gastric mucosal injury induced by H. pylori infection in gerbils, through the inhibition of accumulation of activated neutrophils. Show more

Keywords: Helicobacter pylori, vitamin E, adhesion molecules, gastritis

Citation: BioFactors, vol. 28, no. 1, pp. 9-19, 2006

Authors: Wolfram, Roswitha M. | Budinsky, Alexandra C. | Eder, Andreas | Presenhuber, Christiane | Nell, Andrea | Sperr, Wolfgang | Sinzinger, Helmut

Article Type: Research Article

Abstract: Isoprostanes (IPs) are indicators of in-vivo oxidative stress, and have been successfully used as markers for chronic inflammatory processes. The presence of chronic periodontal disease and cigarette smoking has been individually linked to the development of atherosclerosis, yet data regarding oxidative stress in this context are not available yet. The aim of this study was to evaluate levels of the salivary prostaglandins (PGs) 8-epi-PGF_{2&alpha;} , 6-oxo-PGF_{1&alpha;} , thromboxane B_{2} …(TXB_{2}) and PGF_{2&alpha;} in association with periodontal disease status with and without additional cigarette smoking. We analyzed saliva samples from 121 adults, (aged 21–73 years, 90 non-smokers, 31 smokers) for levels of 8-epi-PGF_{2&alpha;} , 6-oxo-PGF_{1&alpha;} , TXB_{2} and PGF_{2&alpha;} . On the basis of periodontal disease indices the periodontal status of each subject was assessed and outcomes were then correlated with smoking status and laboratory findings. Salivary 8-epi-PGF_{2&alpha;} levels increased with deteriorating plaque index, and were significantly higher (115.5 ± 23.5 pg/ml) in smoking individuals, when compared to non-smokers (70.2 ± 20.4 pg/ml, p<0.0001). In addition, smokers showed higher TXB_{2} and PGF_{2&alpha; s} and lower 6-oxo-PGF_{1&alpha;} levels p<0.0001). Oxidative stress, as reflected by elevated salivary 8-epi-PGF_{2&alpha;} levels, is associated with the extent of periodontal disease and is significantly aggravated by concomitant tobacco abuse. Chronic inflammation and smoking have been individually associated with the development of atherosclerosis. The results of this study indicate that: 1) salivary IPs can reliably assess the degree of oxidative stress, and: 2) smoking and periodontal disease are two modifiable cardiovascular risk factors, able to potentiate each other. Show more

Keywords: Oxidative stress, salivary isoprostanes, periodontital disease, smoking

Citation: BioFactors, vol. 28, no. 1, pp. 21-31, 2006

Authors: Miller, Kevin B. | Caton, Joel S. | Finley, John W.

Article Type: Research Article

Abstract: It has previously been reported that moderately high dietary manganese (Mn) in combination with marginal magnesium (Mg) resulted in ultrastructural damage to heart mitochondria. Manganese may replace Mg in biological functions, including the role of enzyme cofactor. Manganese may accumulate and substitute for Mg during the condition of Mg-deficiency. The objective of the current study was to determine whether high Mn alters heart muscle respiration and Mg-enzyme activity as well as whole body Mn retention …under marginal Mg. An additional objective was to determine whether high Mn results in increased oxidative stress. In experiment 1: forty-eight rats were fed a 2 × 3 factorial arrangement of Mn (10, 100, or 1000 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2: thirty-two rats were fed one of four diets in a 2 × 2 factorial arrangement of Mn (10 or 250 mg/kg) and Mg (200 or 500 mg/kg). In experiment 3: thirty-two rats were fed one of four diets in a 2 × 2 factorial arrangement of Mn (10 or 650 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2, high Mn and marginal Mg reduced (P<0.05) oxygen consumption of left ventricle muscle. Marginal Mg, but not Mn, reduced (P<0.05) activity of sarcoplasmic reticulum calcium-ATPase enzyme. Dietary Mg had no affect on ^{54} Mn kinetics, but high dietary Mn decreased (P<0.01) absorption, retention, and rate of excretion of ^{54} Mn. Neither cellular stress, measured by Comet assay, nor antioxidant activities were increased by high Mn. A strong interaction (P<0.001) between increasing Mn and adequate Mg on hematology was observed. These results confirm previous research in swine that high Mn alters myocardial integrity as well as function, but not as a result of altered calcium transport or oxidative stress. Show more

Keywords: Manganese, magnesium, rat, heart, mitochondria

Citation: BioFactors, vol. 28, no. 1, pp. 33-46, 2006

Authors: Niklowitz, Petra | Andler, Werner | Menke, Thomas

Article Type: Research Article

Abstract: Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant and performs essential functions in mitochondrial energy production. The value of CoQ10 as a biomarker for oxidative stress will be severely restricted if there are huge individual daily variations in its concentration. For analysis of diurnal changes in CoQ10 plasma and blood cell concentrations, blood was collected from nine healthy adults (at two- or three-hour intervals for plasma, and three times a day for …blood cells). CoQ10 was analysed by HPLC using electrochemical detection and internal standardisation. Daytime variations in CoQ10 concentration in plasma are maintained within narrow limits and show no statistically significant difference (Kruskal-Wallis). However, a drop at night-time (0300 h) is accompanied by a drop in total cholesterol concentration. Remarkable inter-individual differences in blood cell (erythrocytes, platelets, white blood cells) content of CoQ10 occur with only slight intra-individual daily variations. A correlation (Spearman) is found for cholesterol and CoQ10 content in circulation which may be explained by the carrier capacity of blood for this highly lipophilic substance. Moreover, a diurnal change in hepatic HMG-CoA reductase activity may suggest a common diurnal regulation of synthesis of both CoQ10 and cholesterol. Show more

Keywords: Coenzyme Q10, plasma, erythrocytes, platelets, white blood cells, daily changes

Citation: BioFactors, vol. 28, no. 1, pp. 47-54, 2006

Authors: Oosthuizen, Mathys M.J. | Lambrechts, Hugo

Article Type: Research Article

Abstract: Hepatoproliferin (HPF), a liver regeneration factor, was isolated initially as an aggregated molecule (big-HPF) and was purified into two homogeneous, bioactive species of 14 kDa and 18.5 kDa. These two big-HPFs were disaggregated to completion into two monomeric forms (small-HPFs) when incubated for 10 days in 0.15 M ammonium bicarbonate at 25°C. Both monomeric forms were purified to homogeneity as active entities, one with a molecular mass of 944 Da and one with a molecular mass …of 1066 Da. Each of the two ^{35} S-labelled small-HPFs was found, by enzymic analysis, to contain a charged sulfonated saccharide, which was neutralized by a specific amine. Monomeric HPF is therefore a stable ionic complex formed between these two ionic species. So strong was the electrostatic association that small-HPF remained intact in solution and no amine was displaced by the ammonium ions of the buffer. Small-HPF remained unimpaired during purification, since all activity was retained despite alternating acidic and basic conditions. However, when small-HPF was brought into contact with either a cationic or an anionic resin, it was dissociated to completion when mixed continuously with the resin for 4 days. The ionic entity that was released had no bio-activity and was either a pure radioactively labeled saccharide or a non-labeled amine, depending on the kind of resin used. When incubated together, the separated counterions combine to regain full activity after 2 days of reassociation. However, with incubation for longer, this reassociated small-HPF formed different oligomeric HPFs by aggregation. Small-HPF is therefore a new kind of growth enhancer, consisting of an acidic sulfonated saccharide and a basic amine assembled into a stable active ionic complex that has a tendency to aggregate. Show more

Keywords: Big-HPF, oligomerization, self-aggregation, small-HPF, solid-phase dissociation

Citation: BioFactors, vol. 28, no. 1, pp. 55-70, 2006