Several reports suggest that obesity is a risk factor for osteoporosis. Vitamin K plays an important role in improving bone metabolism. This study examined the effects of vitamin K1 and vitamin K2 supplementation on the biochemical markers of bone turnover and morphological microstructure of the bones by using an obese mouse model. Four-week-old C57BL/6J male mice were fed a 10% fat normal diet group or a 45% kcal high-fat diet group, with or without 200 mg/1000 g vitamin K1 (Normal diet + K1, high-fat diet + K1) and 200 mg/1000 g vitamin K2 (Normal diet + K2, high-fat diet + K2) for 12 weeks.
Serum levels of osteocalcin were higher in the high-fat diet + K2 group than in the high-fat diet group. Serum OPG level of the high-fat diet group, high-fat diet + K1 group, and high-fat diet + K2 group was 2.31 ± 0.31 ng/ml, 2.35 ± 0.12 ng/ml, and 2.90 ± 0.11 ng/ml, respectively. Serum level of RANKL in the high-fat diet group was significantly higher than that in the high-fat diet + K1 group and high-fat diet + K2 group (p<0.05). Vitamin K supplementation seems to tend to prevent bone loss in high-fat diet induced obese state. These findings suggest that vitamin K supplementation reversed the high fat diet induced bone deterioration by modulating osteoblast and osteoclast activities and prevent bone loss in a high-fat diet-induced obese mice.
vitamin K; obesity; bone density; osteoblast; osteoclast
It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism.
diabetes mellitus type 2; S-allyl cysteine; OLETF; PPAR; SREBP-1c
Excessive generation of reactive oxygen species within cells results in oxidative stress. Furthermore, accumulation of reactive oxygen species has been shown to reduce cell longevity. Many dietary supplements are believed to have anti-aging effects. The herb mixture KPG-7 contains several components with antioxidant activity. We aim to clarify the mechanisms responsible for the antioxidant activity of KPG-7 and to establish whether KPG-7 has an anti-aging effect. We examined whether dietary supplementation with KPG-7 could provide protection against oxidative stress, extend lifespan, and delay aging in Caenorhabditis elegans (C. elegans). We found that KPG-7 extended lifespan and delayed aging in adult C. elegans. The expression of oxidation resistance 1 protein was induced by juglone and this effect was significantly suppressed in KPG-7-treated. In addition, the amount of oxidized protein was significantly lower in KPG-7-treated worms than untreated worms. Furthermore, locomotive activity was increased in C. elegans at 3 days of age following the treatment with KPG-7. On the other hand, the level of cellular ATP was lower at 3 days of age in worms treated with KPG-7 than in untreated worms. KPG-7 increases lifespan and delays aging in C. elegans, well corresponding to its activity to protect against oxidative stress.
oxidative stress; C. elegans; aging; herb mixture; antioxidant
We investigated the effects of treatment with antibodies against tumor necrosis factor (TNF)-α on energy metabolism, nutritional status, serum cytokine levels in patients with Crohn’s disease (CD). Twelve patients were enrolled. Resting energy expenditure (REE) levels were measured by indirect calorimetry. Crohn’s disease activity index (CDAI) significantly decreased after treatment with anti-TNF-α therapy. Anti-TNF-α therapy did not affect REE, but respiratory quotient (RQ) significantly increased after treatment. Serum interleukin-6 levels were significantly decreased and RQ were significantly increased in high REE (≥25 kcal/kg/day) group as compared to low REE (<25 kcal/kg/day) group. In conclusion, high REE value on admission is a predictive factor for good response to treatment with anti-TNF-α antibodies in active CD patients.
Crohn’s disease; energy metabolism; indirect calorimetry; infliximab; adalimumab
Rabbits with hereditary postprandial hypertriglyceridemia exhibit central obesity and are regarded as a reliable model for metabolic syndrome. This study was performed to gain insight into the affected process of lipid metabolism and into the causative genes of the postprandial hypertriglyceridemia rabbits. Eleven genes that play key roles in lipid metabolism were selected, their mRNA levels were assessed by quantitative PCR, and their expressions were compared among postprandial hypertriglyceridemia rabbits using Japanese white rabbits as the control. Two genes appeared to be in causal connection with postprandial hypertriglyceridemia, and these were regarded as likely candidates for the pathogenesis. One was the fatty acid synthase gene, which had an expression constitutively higher in postprandial hypertriglyceridemia rabbits than in Japanese white rabbits during the fasting state and reached quite high levels after feeding. The other was the gene for hepatic triglyceride lipase with an expression that was approximately one order lower than that found in the Japanese white rabbits. The low plasma hepatic triglyceride lipase activities were consistent with the low levels of the transcript in the livers of the postprandial hypertriglyceridemia rabbits. Thus, elevated fatty acid synthesis and defected lipid hydrolysis together would cause the postprandial hypertriglyceridemia in postprandial hypertriglyceridemia rabbits.
postprandial hypertriglyceridemia; metabolic syndrome; hepatic triglyceride lipase; fatty acid synthase
Mithramycin A (Mith) is an aureolic acid-type polyketide produced by various soil bacteria of the genus Streptomyces. Mith inhibits myeloid cell leukemia-1 (Mcl-1) to induce apoptosis in prostate cancer, but the molecular mechanism underlying this process has not been fully elucidated. The aim of this study was therefore to investigate the detailed molecular mechanism related to Mith-induced apoptosis in prostate cancer cells. Mith decreased the phosphorylation of mammalian target of rapamycin (mTOR) in both cell lines overexpressing phospho-mTOR compared to RWPE-1 human normal prostate epithelial cells. Mith significantly induced truncated Bid (tBid) and siRNA-mediated knock-down of Mcl-1 increased tBid protein levels. Moreover, Mith also inhibited the phosphorylation of mTOR on serine 2448 and Mcl-1, and increased tBid protein in prostate tumors in athymic nude mice bearing DU145 cells as xenografts. Thus, Mith acts as an effective tumor growth inhibitor in prostate cancer cells through the mTOR/Mcl-1/tBid signaling pathway.
prostate cancer; Mithramycin A; myeloid cell leukemia-1; mTOR; truncated Bid
Alcohol/ethanol has been reported to derived necrosis and apoptosis with an oxidative stress in gastric mucosal cells. However the clear evidence for reactive oxygen species (ROS) generation by alcohol in gastric cells in vitro is none. In this study, we elucidated ethanol is an oxidative stress inducer on rat gastric epithelial cells by electron paramagnetic resonance measurement in living cells. We also confirmed whether ethanol-induced cellular ROS was derived from mitochondria or not. The results of cellular ROS determination showed that an increment of cellular ROS was shown for 15 min from exposing 1% (v/v) ethanol. Lipid peroxidation in cellular membrane also induced by 1% ethanol and the tendency is same in the results of cellular ROS determination. JC-1 stained showed the decrement of mitochondrial membrane potential. Additionally the localization of cellular ROS coincided with mitochondria. These results indicated that ethanol is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer via injured mitochondria.
alcohol; reactive oxygen species; mitochondria; stomach cells; Electron Paramagnetic Resonance
Only a few investigations were based on limb bone density. This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders, limb bone density and the role of pathway. The research protocol involved the random subdivision of the enrolled sample into two groups of 40 women, who were to receive treatment for 6 months with isoflavone (90 mg/day) and with placebo. All of the patients were asked to fill in a questionnaire concerning their complaints. BMD of the radius and tibia were measured using quantitative ultrasound. Bone metabolism indexes calcium, phosphorus and alkaline phosphatase (ALP) were examined regularly. Serum cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) examined by ELISA. The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders. Compared with placebo, the tibia bone density in isoflavone group increased obviously against the base value before trail. Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo. For climacteric women, soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density, which maybe had the relationship with the levels of IL-6, TNF-α and ALP in serum.
soy isoflavone; climacteric women; bone mineral density; serum cytokines; bone metabolism indexes
Exposure to asbestos fibers increases the risk of mesothelioma in humans. One hypothetical carcinogenic mechanism is that asbestos fibers may directly induce mutations in mesothelial cells. Although the uptake of asbestos fibers by mesothelial cells is recognized, methods for the quantification of the uptake have not been well established. In the present study, we evaluated two distinct methods, using crocidolite fibers and MeT5A mesothelial cells. One method is histological evaluation using the cell-block technique, which allows for the direct cross-sectional observation of cells and fibers. We found the bright field observation with ×1000 magnification (oil-immersion) of the sample with Kernechtrot staining was most suitable for this purpose. The other method is flow cytometric analysis, which permits the evaluation of a much larger number of cells. We observed that the side scatter (SSC) increased with the intracellular fibers, and that the “mean SSC ratio (treated/control)” was useful for quantification. We could collect the cells with abundant internalized crocidolite fibers by sorting. Results of the two methodologies were correlated well in the experiments. The quantities of internalized fibers increased with incubation time and loaded dosage, but they were inversely associated with cellular density in culture.
flow cytometry; cell-block; crocidolite; endocytosis; quantitative assessment
Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.
permeability; diclofenac; small intestinal damage; rebamipide; healthy subjects
S-equol is a natural metabolite of the soy isoflavone, daidzein, produced by intestinal bacteria. S-equol has been shown to have greater estrogenic activity than other soy isoflavones and prevent bone loss in post-menopausal women. Estrogen regulates both bone remodeling and hemopoiesis in the bone marrow, these processes that communicate closely with each other. In this study, we investigated the effect of S-equol on bone mass and gene expression of bone marrow cells in ovariectomized (OVX) mice. Female ddY strain mice, aged 12 weeks, were either sham operated or OVX. The OVX mice were randomly divided into two groups: (1) OVX control and (2) OVX fed a 0.06% (w/w) S-equol supplemented diet. After 2 weeks, the trabecular bone volume of the femoral distal metaphysis was markedly reduced in OVX mice. However, treatment with equol was observed to ameliorate this. Expression of inflammatory-, osteoclastogenesis- and adipogenesis-related genes was increased in OVX mice compared with sham mice, and equol was observed to suppress their expression. The present study demonstrates that equol might ameliorate bone loss caused by estrogen deficiency through regulating hemopoiesis and production of inflammatory cytokines in bone marrow cells.
S-equol; isoflavone; bone loss; inflammatory related gene; ovariectomized mice
Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury.
middle cerebral artery occlusion; pre-conditioning exercise; oxidative stress; sensori-motor function; rat
Recent studies have indicated that non-steroidal anti-inflammatory drug (NSAID), particularly tolfenamic acid, can inhibit proliferation and induce apoptosis invarious cancer cells. Breast cancer represents one-third of all cancers diagnosed in women and is the second leading cause of cancer death in Western European and North American women. In the present study, we investigated the apoptotic effect of tolfenamic acid in MDA-MB-231 estrogen receptor-negative human breast carcinoma cells and in a xenograft tumor model. Treatment of cells with tolfenamic acid significantly decreased cell viability in a concentration-dependent manner. Notably, tolfenamic acid increased apoptosis-related proteins, such as p53 and p21, within 48 h. Furthermore, in vivo experiments showed that tolfenamic acid treatment resulted in a significant reduction in tumor volume over 5 weeks. Immunohistochemistry results showed that apoptosis-related protein induction by tolfenamic acid was significantly higher in the 50 mg/kg-treated group compared to the control group. Together, these results indicate that tolfenamic acid induces apoptosis in MDA-MB-231 breast cancer cells and tumor xenograft model and it may be a potential chemotherapeutic agent against breast cancer.
tolfenamic acid; MDA-MB-231; apoptosis; p53; p21
The fatty acid composition of serum phospholipids were analyzed in 20 patients with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable nutritional status); 25 healthy age and sex-matched adults were used as controls. Cirrhotic patients showed higher levels of palmitic acid and total saturated fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and docosahexaenoic acid were significantly lower (p<0.001) in patients with alcoholic cirrhosis compared to healthy controls. Significant changes were also found between patients stratified according to nutritional status. In particular, the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty acids was higher (p<0.01) in malnourished patients when compared to the patients with acceptable nutritional status. Furthermore, important changes in the levels of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were found in well-nourished patients with alcoholic cirrhosis as well. Our present data confirmed evidence that malnutrition is one of the factors that led to lower levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis. PUFA supplementation in the latter needs further investigation.
phospholipids fatty acid; alcohol; cirrhosis; malnutrition
The present study aimed to assess the effect of supplementation of omega-3 and/or vitamin C on serum interleukin-6 and high sensitivity C-reactive protein concentration and depression scores among shift workers in Shahid Tondgoyan oil refinery. The study design was randomized, double-blind, placebo-controlled, parallel trial. Totally 136 shift workers with a depression score ≥10 in 21-item Beck Depression Rating Scale were randomly assigned to receive omega-3 (180 mg eicosapentaenoate acid and 120 mg docosahexaenoic acid) or/and vitamin C 250 mg or placebo twice daily (with the same taste and shape as omega-3 and vitamin C) for 60 days in four groups. Depression score, interleukin-6 and high sensitivity C-reactive protein were measured at baseline and after 60 days. This study showed that supplementation of omega-3 plus vitamin C is associated with a decrease in depression score (p<0.05). Supplementation of omega-3 without vitamin C, is associated with a reduction in depression score (p<0.0001) and high sensitivity C-reactive protein concentration (p<0.01). Therefore omega-3 supplementation showed a better effect on reducing depression score and high sensitivity C-reactive protein, but supplementation of vitamin C along with omega-3 did not have significant effect on change in C-reactive protein level compared to omega-3 alone. (Registration number: IRCT201202189056N1)
omega-3 fatty acids; vitamin C; interleukin-6 (IL-6); high sensitivity C-reactive protein (hs-CRP); depression
Static electric field therapy by high voltage alternating current (EF-HVAC) is a traditional complementary Japanese medicine used for headache, shoulder stiffness, chronic constipation and insomnia. Open-label studies and clinical experience in Japan have suggested that this electric field therapy is safe and effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC therapy in a randomized, double-blinded, sham-controlled trial in patients with active rheumatoid arthritis (RA) in community-based general physician centers. Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp., Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory parameters were used as the outcome variable. Twenty four patients (n = 12 in each group) were analyzed by a per protocol analysis. Although a significant reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared to before treatment, there were no significant differences in DAS28-CRP scores during treatment between two groups. The scale of VAS was also significantly decreased by the treatment with EF-HVAC compared to before treatment, in addition, the scale of VAS in EF-HVAC group was significantly lower than sham group at 8 and 12 weeks. Changes in another parameters including MHAQ were not significant between before and after treatment, or by all comparative study between two groups. There were no adverse events related the treatment. In conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to subjective pain of RA.
static electric field; rheumatoid arthritis; disease activity score; visual analogue scale
This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60–180 min; p<0.05), as a result of significant increases in insulin secretion (0–180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15–60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability.
liraglutide; insulin; glucagon; test meal; continuous glucose monitoring
Recent studies have suggested that decrease in Helicobacter pylori infection may predispose to allergic diseases. However, there are few reports of the relationships of eosinophilic gastrointestinal disorders (EGIDs), especially eosinophilic gastroenteritis (EGE), with H. pylori infection. We investigated the possible influence of H. pylori infection on EGIDs in Japanese patients. We performed a case-control study to investigate the prevalence of H. pylori infection in patients with EGIDs. Eighteen with eosinophilic esophagitis (EoE) and 22 with EGE were enrolled. For each patient, 3 age- and gender-matched normal controls (n = 120) were randomly selected from a population who received a medical check-up between April 2010 and December 2011 at the Shimane Institute of Health Science. The mean ages of the EoE and EGE patients were 50.9 ± 17 and 49.2 ± 20 years, respectively. Males were more frequently seen in the EoE group, while there was no significant gender difference in regard to EGE. Of the patients with EoE, 22.3% were infected with H. pylori, as compared to 55.5% of their age- and sex-matched normal controls. The odds ratio for EoE patients to have an H. pylori infection was 0.22 (p<0.05). In addition, 22.7% of the patients with EGE and 48.5% of their matched controls were infected with H. pylori, with odds ratio for EGE patients to have an H. pylori infection shown to be 0.31 (p<0.05). In conclusion, the prevalence of H. pylori infection was significantly lower in EGE and EoE patients in Japan as compared to normal control subjects.
eosinophilic esophagitis; eosinophilic gastroenteritis; Helicobacter pylori infection; Th2
Chronic kidney disease (CKD) is well known as a strong risk factor for both of end-stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in the genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD, SEPP1, SEP15 and SELS) with the risk of CKD in Japanese, we examined this association using the cross-sectional data of Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The subjects were 3,285 men and women, aged 35–69 years, selected from J-MICC Study participants for whom genotyping were conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3–5 (eGFR <60 ml/min/1.73 m2). When those with CAT C-262T C/C were defined as reference, those with CAT C-262T C/T demonstrated the OR for CKD of 0.67 (95% CI 0.43–1.06) with the marginally significant trend for decreased odds ratio with increasing numbers of T allele (p = 0.070). There were no significant associations between the other polymorphisms with CKD risk. The present study found a marginally significant trend of the decreased risk of CKD with increasing numbers of T allele of CAT, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.
antioxidant enzymes; genetic predisposition to disease; single nucleotide polymorphisms; chronic kidney disease
We evaluated the antioxidative effects of astaxanthin through the changes in superoxide scavenging activity, levels of hydrogen peroxide and total hydroperoxides in human aqueous humor. The study subjects were 35 patients who underwent bilateral cataract surgery on one side before and the other side after intake of astaxanthin (6 mg/day for 2 weeks). Their aqueous humor was taken during the surgery and subjected to measurements of the three parameters. After astaxanthin intake, the superoxide scavenging activity was significantly (p<0.05) elevated, while the level of total hydroperoxides was significantly (p<0.05) lowered. There was a significant negative correlation between the superoxide scavenging activity and the level of total hydroperoxides (r = −0.485, p<0.01), but no correlations between the hydrogen peroxide level and the other two parameters. Astaxanthin intake clearly enhanced the superoxide scavenging activity and suppressed the total hydroperoxides production in human aqueous humor, indicating the possibility that astaxanthin has suppressive effects on various oxidative stress-related diseases.
astaxanthin; aqueous humor; superoxide; hydrogen peroxide; oxidation
In the past few decades, many types of functional factors have been identified in dietary foods; for example, flavonoids are major groups widely distributed in the plant kingdom. However, the absorption rates of the functional food factors are usually low, and many of these are difficult to be absorbed in the intact forms because of metabolization by biological processes during absorption. To gain adequate beneficial effects, it is therefore mandatory to know whether functional food factors are absorbed in sufficient quantity, and then reach target organs while maintaining beneficial effects. These are the reasons why the bioavailability of functional food factors has been well investigated using rodent models. Recently, many of the biological processes have been reported to follow diurnal rhythms recurring every 24 h. Therefore, absorption and metabolism of functional food factors influenced by the biological processes may vary with time of day. Consequently, the evaluation of the bioavailability of functional food factors using rodent models should take into consideration the timing of consumption. In this review, we provide a perspective overview of the diurnal rhythm of biological processes involved in the bioavailability of functional food factors, particularly flavonoids.
bioavailability; diurnal rhythmicity; flavonoids; functional food factors; rodents
Lipid peroxidation products are known to cause toxicity by reacting with biologically significant proteins, but the inducing role of peroxidation products has been not noted to produce degenerative disease-related eicosanoids. Here, 9-oxononanoic acid (9-ONA), one of the major products of peroxidized fatty acids, was found to stimulate the activity of phospholipase A2 (PLA2), the key enzyme to initiate arachidonate cascade and eicosanoid production. An exposure of fresh human blood to the atmosphere at 37°C accumulated 9-ONA, increasing peroxide value and thiobarbituric acid reactive substances in the blood. The lipid peroxidation was accompanied by significant increases of PLA2 activity and thromboxane B2 (TxB2) production, which is a stable metabolite of thromboxane A2 (TxA2) and a potent agonist of platelet aggregation. These events were abolished by standing the blood under nitrogen. The addition of organically synthesized 9-ONA resumed the activity of PLA2 and the production of TxB2. Also, 9-ONA induced platelet aggregation dose-dependently. These results indicated that 9-ONA is the primary inducer of PLA2 activity and TxA2 production, and is probably followed by the development of diseases such as thrombus formation. This is the first report to find that a lipid peroxidation product, 9-ONA, stimulates the activity of PLA2.
9-oxononanoic acid; lipid peroxidation; phospholipase A2; thromboxane A2; arachidonate cascade