Oxidized low-density lipoprotein is known as an important factor in the development of atherosclerosis. The introduction of a sensitive procedure for the determination of oxidized low-density lipoprotein in human circulating plasma using a monoclonal antibody recognizing oxidized phosphatidylcholines has opened new fields of research based on in vivo oxidized low-density lipoprotein. The plasma oxidized low-density lipoprotein levels are significantly elevated in patients with acute myocardial infarction, cerebral infarction or chronic renal failure accompanied by hemodialysis. It was found that the plasma oxidized low-density lipoprotein level increased prior to aortic atherosclerotic lesion enlargement in apolipoprotein E-knockout mice. Recent studies have pointed out that oxidized low-density lipoprotein is transferrable between vessel wall tissue and the circulation, so it is a reasonable hypothesis that plasma oxidized low-density lipoprotein levels reflect the oxidative status at local sites of atherogenesis. Oxidized low-density lipoprotein measurement has been applied to human gingival crevicular fluids, which can be collected easily and safely, and relatively high levels of oxidized low-density lipoprotein were shown to be present. These findings, together with recent clinical follow-up studies, suggest that oxidized low-density lipoprotein is a predictive biomarker of a variety of diseases related to oxidative stress. This review summarizes the current understanding of in vivo oxidized low-density lipoprotein and its potential significance as a biomarker of disease.
We have developed a new disinfection system for oral hygiene, proving that hydroxyl radicals generated by the photolysis of 1 M hydrogen peroxide could effectively kill oral pathogenic microorganisms. Prior to any clinical testing, the safety of the system especially in terms of the risk of carcinogenicity is examined by reviewing the literature. Previous studies have investigated indirectly the kinds of reactive oxygen species involved in some sort of chemically-induced mutagenicity in vitro by using reactive oxygen species scavengers, suggesting the possible involvement of hydroxyl radicals. Similarly, possible involvement of hydroxyl radicals in some sort of chemically-induced carcinogenicity has been proposed. Notably, it is suggested that the hydroxyl radical can play a role in heavy metal-induced carcinogenicity that requires chronic exposure to the carcinogen. In these cases, hydroxyl radicals produced by Fenton-like reactions may be involved in the carcinogenicity. Meanwhile, potential advantages have been reported on the use of the hydroxyl radical, being included in host immune defense by polymorphonuclear leukocytes, and medical applications such as for cancer treatment and antibiotics. From these, we conclude that there would seem to be little to no risk in using the hydroxyl radical as a disinfectant for short-term treatment of the oral cavity.
The aim of this study was to investigate the influence of rice bran oil consumption on plasma lipids and insulin resistance in patients with type 2 diabetes. Thirty-five patients with type 2 diabetes were randomly assigned to a placebo group or a rice bran oil group. The placebo group consumed 250 mL soybean oil-modified milk (18 g soybean oil) daily for 5 weeks, and the rice bran oil group consumed 250 mL rice bran oil modified milk (18 g rice bran oil) daily for 5 weeks. At week 0 and week 5, anthropometric measurements, hematology tests, and an oral-glucose-tolerance test were conducted. The results showed that the homeostasis model assessment index of insulin resistance, the area under the curve for postprandial serum insulin, and serum low-density-lipoprotein cholesterol concentrations increased significantly in the placebo group. In the rice bran oil group, fasting and 2-h postprandial blood glucose concentrations and the area under the curve for postprandial plasma glucose increased significantly; however, total serum cholesterol and low-density-lipoprotein cholesterol concentrations decreased significantly. However, the homeostasis model assessment index of insulin resistance was not significantly different. Consumption of 18 g rice bran oil modified milk daily for 5 weeks significantly decreased total serum cholesterol concentrations and tended to decrease low-density-lipoprotein cholesterol concentrations in patients with type 2 diabetes. However, no significant influence on insulin resistance was observed.
The role of gamma amino butyric acid A receptors/neurons of the hypothalamic, endocrine and alimentary systems in the food intake seen in hunger was studied in 20 h food-deprived rats. Food deprivation decreased blood glucose, serum insulin and produced hyperphagia. The hyperphagia was inhibited by subcutaneous or ventromedial hypothalamic administration of gamma amino butyric acid A antagonists picrotoxin or bicuculline. Although results of blood glucose was variable, insulin level was increased by picrotoxin or bicuculline. In contrast, lateral hypothalamic administration of these agents failed to reproduce the above changes. Subcutaneous administration of picrotoxin or bicuculline increased gastric content, decreased gastric motility and small bowel transit. In contrast, ventromedial or lateral hypothalamic administration of picrotoxin or bicuculline failed to alter the gastric content but decreased the small bowel transit. The results of alimentary studies suggest that gamma amino butyric acid neurons of both ventromedial and lateral hypothalamus selectively regulate small bowel transit but not the gastric content. It may be concluded that ventromedial hypothalamus plays a dominant role in the regulation of food intake and that picrotoxin or bicuculline inhibited food intake by inhibiting gamma amino butyric acid receptors of the ventromedial hypothalamus, increasing insulin level and decreasing the gut motility.
Hyperphosphatemia causes endothelial dysfunction as well as vascular calcification. Management of serum phosphate level by dietary phosphate restriction or phosphate binders is considered to be beneficial to prevent chronic kidney disease patients from cardiovascular disease, but it has been unclear whether keeping lower serum phosphate level can ameliorate endothelial dysfunction. In this study we investigated whether low-phosphate diet can ameliorate endothelial dysfunction in adenine-induced kidney disease rats, one of useful animal model of chronic kidney disease. Administration of 0.75% adenine-containing diet for 21 days induced renal failure with hyperphosphatemia, and impaired acetylcholine-dependent vasodilation of thoracic aortic ring in rats. Then adenine-induced kidney disease rats were treated with either control diet (1% phosphate) or low-phosphate diet (0.2% phosphate) for 16 days. Low-phosphate diet ameliorated not only hyperphosphatemia but also the impaired vasodilation of aorta. In addition, the activatory phosphorylation of endothelial nitric oxide synthase at serine 1177 and Akt at serine 473 in the aorta were inhibited by in adenine-induced kidney disease rats. The inhibited phosphorylations were improved by the low-phosphate diet treatment. Thus, dietary phosphate restriction can improve aortic endothelial dysfunction in chronic kidney disease with hyperphosphatemia by increase in the activatory phosphorylations of endothelial nitric oxide synthase and Akt.
Biomedical evidence in the last 20 years has shown that the consumption of partially hydrolyzed guar gum may influence lipid and/or carbohydrate metabolism at many levels. Since intestine represents the first interface to interact with dietary partially hydrolyzed guar gum in vivo, we evaluated gene expression profiles in small intestinal mucosa of db/db mice fed with partially hydrolyzed guar gum in an effort to delineate its effect on the small intestine. DNA microarray and real-time PCR analyses were performed to evaluate the gene expression profiles in mice small intestinal mucosa. Among the 28,853 transcripts represented on the GeneChip® microarray, no more than 20 genes exhibited up- or down-regulation by 1.5-fold or more after four weeks following partially hydrolyzed guar gum consumption. No adverse effects were apparent. We detected up- or down-regulation of some genes known to be involved in host defense functions and cholesterol absorption.
Atrophic gastritis is characterized by chronic inflammation of gastric mucosa by Helicobacter pylori infection and other factors. Helicobacter pylori infection has been linked to coronary artery disease. To our knowledge, however, no reports are available on the relationship between atrophic gastritis and coronary artery disease. In this study, we investigated the relationship between atrophic gastritis, which is diagnosed based on serum pepsinogen levels (pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0), and the prevalence of coronary artery disease in general Japanese population. Among 2,633 study subjects, 531 subjects (20.2%) were diagnosed as atrophic gastritis. The prevalence of coronary artery disease was higher in the atrophic gastritis-positive group than that in the atrophic gastritis-negative group (5.8% vs 2.8%, p = 0.0005). Multiple logistic regression analysis demonstrated that atrophic gastritis was independently associated with coronary artery disease (odds ratio, 1.67; 95% confidence interval, 1.03–2.72), after adjustment for age, sex, obesity, hypertension, diabetes mellitus, dyslipidemia, hyperuricemia, and habits of smoking and drinking. These results suggest that atrophic gastritis is an independent risk factor for coronary artery disease. Chronic inflammation of gastric mucosa may be associated with the prevalence of coronary artery disease.
This study explored the effects of the antioxidant astaxanthin on paraoxonase and thioredoxin reductase activities as well as on other oxidative stress parameters and on the lipid profile in hypercholesterolemic rabbits. Rabbits were fed a standard or a hypercholesterolemic diet alone or supplemented with 50, 100 and 500 mg/100 g of astaxanthin for 60 days. Antioxidant enzymes activities, lipid profile and oxidative stress markers were evaluated in the serum. The hypercholesterolemic diet increased lipids, including unsaturated fatty acids level, whereas it decreased saturated fatty acids level. These changes were accompanied by increased levels of oxidized low-density lipoprotein and oxidized low-density lipoprotein antibodies, as well as lipid and protein oxidation. Astaxanthin (100 and 500 mg/100 g) prevented hypercholesterolemia-induced protein oxidation, whereas 500 mg/100 g of astaxanthin decreased protein oxidation per se. The activities of superoxide dismutase and thioredoxin reductase were enhanced, whereas paraoxonase activity was inhibited in hypercholesterolemic rabbits. All astaxanthin doses prevented changes in thioredoxin reductase and paraoxonase activities. This effect was not related to a direct effect of astaxanthin on these enzymes, because in vitro astaxanthin enhanced thioredoxin reductase and had no effect on paraoxonase activity. Astaxanthin could be helpful in cardiovascular diseases by restoring thioredoxin reductase and paraoxonase activities.
The aim of this study was to investigate the possible effects of sulphite oxidase (SOX, E.C. 188.8.131.52) deficiency on xenobiotic metabolism. For this purpose, SOX deficiency was produced in rats by the administration of a low molybdenum diet with concurrent addition of 200 ppm tungsten to their drinking water. First, hepatic SOX activity in deficient groups was measured to confirm SOX deficiency. Then, aminopyrine N-demethylase, aniline 4-hydroxylase, aromatase, caffeine N-demethylase, cytochrome b5 reductase, erythromycin N-demethylase, ethoxyresorufin O-deethylase, glutathione S-transferase, N-nitrosodimethylamine N-demethylase and penthoxyresorufin O-deethylase activities were determined to follow changes in the activity of drug metabolizing enzymes in SOX-deficient rats. Our results clearly demonstrated that SOX deficiency significantly elevated A4H, caffeine N-demethylase, erythromycin N-demethylase and N-nitrosodimethylamine N-demethylase activities while decreasing ethoxyresorufin O-deethylase and aromatase activities. These alterations in drug metabolizing enzymes can contribute to the varying susceptibility and response of sulphite-sensitive individuals to different drugs and/or therapeutics used for treatments.
We previously reported that the all-cis isomer of arachidonic acid, the most naturally occurring isoform of this fatty acid, reduced cuprous copper ion-induced conversion of xanthine dehydrogenase into its reactive oxygen species generating form, xanthine oxidase. In the present study, the effects of all-trans isomer of arachidonic acid, in comparison with cis isomer of arachidonic acid, on the xanthine dehydrogenase/xanthine oxidase interconversion were explored. cis isomer of arachidonic acid alone did not have any significant effect on the activities of xanthine dehydrogenase and xanthine oxidase, but it inhibited the cuprous copper ion-induced conversion of xanthine dehydrogenase to xanthine oxidase in rat liver cytosol in vitro. In contrast, trans isomer of arachidonic acid elicited an increase in xanthine oxidase activity concomitant with a decrease in xanthine dehydrogenase activity, and further potentiated the cuprous copper ion-induced xanthine dehydrogenase/xanthine oxidase interconversion. In primary rat hepatocyte cultures, trans isomer of arachidonic acid increased 2′,7′-dichlorofluorescein-fluorescence intensity in the cytosolic fraction from 2′,7′-dichlorodihydrofluorescein, an indicator of reactive oxygen species generation. The pretreatment of allopurinol, an xanthine oxidase inhibitor, diminished the trans isomer of arachidonic acid-induced increase in the 2′,7′-dichlorofluorescein-fluorescence intensity, indicating the role of xanthine dehydrogenase/xanthine oxidase in mediating trans isomer of arachidonic acid-induced reactive oxygen species generation. These observations suggest that, in contrast to all-cis arachidonic acid, all-trans arachidonic acid has the potential to enhance reactive oxygen species generation via xanthine dehydrogenase/xanthine oxidase interconversion in the liver cytosol in vitro.
Exposure to soy isoflavones has been associated with low mortality of prostate cancer. In this study, we examined the effects of (±)equol and two representative isoflavones, daidzein and genistein, on migration and invasion in human prostate cancer DU145 cells. First of all, the three regents did not show significant growth inhibitive effect in DU145 cells until the treatments last for 72 h. Treatment with 5 μM, 10 μM, 50 μM (±)equol, 0.5 μM, 1 μM, 5 μM daidzein and genistein for 24 h decreased cell migration and invasion significantly. (±)equol activated phosphatase and tensin homologue deleted on chromosome ten at protein level but not mRNA level, which activated antioxidants, including superoxide dismutase and nuclear factor (erythroid-derived 2)-like 2. A reduction of malondialdehyde concentration, the product of lipid per-oxidation, was observed as well. Moreover, matrix metalloproteinase-2, matrix metalloproteinase-9, and urokinase-type plasminogen activator, the crucial members in metastasis, were down-regulated. Overall, our data indicate that (±)equol, daidzein and genistein may have significant anti-invasion effect in DU145 cells (in vitro). The effects induced by (±)equol may relate to its anti-oxidant effect mediated by phosphatase and tensin homologue deleted on chromosome ten.
Recently, arginase is suggested to regulate nitric oxide production by competing with nitric oxide synthase for the same substrate, L-arginine, in experimental asthma. We investigated the role of arginase and its relationship to nitric oxide production after spinal cord injury. Rats were subjected to laminectomy and complete transection of their spinal cords (injury group) or laminectomy only (sham group). In the injury group, arginase I was increased in the macrophages at the transection edge, and the peak was observed 48 h after spinal cord injury. However, nitric oxide production decreased significantly in the injury group despite increased nitric oxide synthase2 mRNA expression compared with the sham group. We also demonstrated the reduction in L-arginine concentrations, which was inversely associated with changes in arginase activity. Therefore, arginase appeared to regulate nitric oxide production by consuming L-arginine. The regulation of arginase activity and L-arginine levels may improve nitroxidative stress and reduce tissue damage in spinal cord injury.