Selenium is a trace element essential for the normal function of the body. This metalloid is quite unique in its metabolism compared with typical essential metals such as copper and zinc. In the present communication, the metabolism of selenium in the body was reviewed from the viewpoint of metabolomics based on speciation studies. Both inorganic and organic forms of slenium can be the nutritional source, and they are transformed to the common intermediate, selenide or its equivalent. Selenite and selenate are reduced simply to selenide for further utilization and/or excretion. On the other hand, organic selenocysteine is directly lysed to selenide, while selenomethionine is transformed to selenocysteine (trans-selenation pathway), similarly to the trans-sulfuration pathway for methionine to cysteine, and then lysed to selenide. Selenide is known to be transformed to selenocysteine on tRNA, and the selenocysteinyl residue is incorporated into selenoprotein sequences by the codon specific to selenocysteine, UGA. Diverse selenium chemicals in foods seem to be recognized as selenium species and transformed to selenide, and then utilized for the synthesis of selenoproteins. Surplus selenium is methylated stepwise to methylated selenium metabolites from the common intermediate selenide. The major urinary metabolite is 1β-methylseleno-N-acetyl-D-galactosamine (selenosugar). Trimethylselenonium has been recognized as the urinary metabolite excreted in response to excessive doses and as a biological marker for excessive doses. However, recent results contradicted this.
To examine the effects of an HIV/AIDS educational intervention among young Chinese adults in Hong Kong, we carried out a study among a group of 118 young subjects (most aged 18-25 years). Subjects were recruited from a service force and were assigned to intervention and control groups. Respondents in the intervention group attended one 90-min educational session. At baseline there was no significant difference in different variables among participants in the study. At follow-up four months later, participants in the HIV/AIDS intervention group had increased knowledge of AIDS, more positive attitudes towards AIDS prevention, held higher perception of sexually transmitted disease (STD) risk, showed higher intention to use condoms with regular and irregular partners and talked more with friends about safer sex. Respondents in the control group had more positive attitudes towards AIDS prevention and held higher perception of illness risk with no other significant changes. This first intervention study among young Chinese adults in Hong Kong identified the usefulness and limitations of an HIV/AIDS educational program. The effectiveness and limitation of the current intervention serve as an initial attempt in conducting similar studies in the future targeting the Chinese youth.
The quenching abilities of sodium L-ascorbyl-2-phosphate (APS) and ascorbic acid 2-glucose (AG) against UVB/A-generated free radicals in cultured mouse skin were investigated using electron spin resonance (ESR). The relation between their quenching ability and protective effects against photodamage were also compared to those of ascorbic acid (AsA) pretreatment. Both APS and AG were able to scavenge UVB/A-generated hydroxyl radicals under aqueous conditions (pH 7.2) in a manner similar to that seen with AsA; however, APS was a more effective scavenger than AG. Similar results were obtained ex vivo. Both derivatives could protect skin from UVB/A-induced photodamage, as determined by a reduction in the presence of sunburn cells and DNA fragmentation. However, AsA pretreatment had the weakest protective effect, even though cutaneous, its level was the highest among the three agents tested before irradiation. These results indicated that the superior protective effect of APS is related to its direct free radical scavenging ability, rather than to its conversion to AsA.
The inhabitants living in a specific region of Kizaki area in Kamisu-town, Ibaraki Prefecture exhibited uncommon clinical central nervous system symptoms. A graphite furnace atomic absorption spectrophotometer detected markedly elevated concentration of arsenic (4.5 ppm) in their drinking well water. Further investigation using HPLC, GC/MS and HPLC/ICP/MS demonstrated that the structures of the arsenic were bis(diphenylarsine)oxide (BDPAO), diphenylarsinic acid (DPAA) and phenylarsonic acid (PAA), compounds that can be derived from the chemical warfare agents, diphenylchloroarsine (DA) and diphenylcyanoarsine (DC). The predominant form of the arsenic compound in the well water was DPAA (maximum 15 ppm), so that it was calculated that the inhabitants ingested 11-30 mg of DPAA daily. This is the first report of inhabitants that were injured by drinking well water contaminated with organic arsenic compounds that were likely derived from chemical weapons.
We investigated the influence of dietary protein levels on the fate of methylmercury (MeHg) in rats, and the difference in its urinary excretion was discussed from the viewpoint of the dietary protein level-dependent alteration in activity of the neutral amino acid transport system, through which MeHg metabolites such as MeHg-L-cysteine are reabsorbed, at the renal brush border membrane. When MeHg was administered to rats fed either a 24.8% protein diet (normal protein diet, NPD) or a 7.5% protein diet (low protein diet, LPD), urinary Hg excretion was much lower in LPD-fed rats than in NPD-fed rats, whereas no difference was observed in fecal excretion 1 day after MeHg administration. At that time, Hg concentrations in the brain and plasma were similar in the two dietary groups, whereas the concentrations in liver and blood were higher, but the renal concentration was lower in LPD-fed rats than in NPD-fed rats. Regardless of the presence of Na+, uptake of 14C-L-phenylalanine for the first 20 sec was higher in the renal brush border vehicles from LPD-fed rats than in those from NPD-fed rats. These results suggest that dietary protein deficiency enhances the neutral amino acid transport at the renal brush border membrane, which could lead efficient reabsorption of MeHg metabolites from the proximal luminal space, and it might play a key role in the marked decrease in urinary excretion of MeHg.
The endogenous level of γ-hydroxybutyric acid (GHB) and the in vitro production of GHB in blood from healthy humans have been investigated. The endogenous GHB concentrations in aseptically collected whole blood samples ranged from 5 to 10 ng/ml, which were far below the previously-reported “endogenous” levels . Also, the levels of in vitro GHB production during storage for 16 months at 4°C were lower than 0.4 μg/ml, which were much lower than those in postmortem samples previously reported. Based on the results of this investigation, the authors concluded that an interpretative cutoff of 1.0 μg/ml would be appropriate for differentiating exogenous from endogenous GHB, if only limited to in-life blood specimens that were collected aseptically, stored at 4°C or lower, examined within two weeks, and excludes the possibility of GHB aciduria.
Spontaneous ultra-weak photon emission and delayed luminescence were measured from the mouse liver injured by carbon tetrachloride (CCl4), a hepatotoxic chemical. After carbon tetrachloride in olive oil (4 ml/kg) was injected intraperitoneally into ICR mouse, spontaneous photon emission and delayed luminescence using metal halide lamp was measured from the excised liver. Twenty-four hours after injection, spontaneous photon emission from the livers was 69.3 ± 21.2 counts/min/cm2, which was two times higher than that from controls of 29.5 ± 5.9 counts/min/cm2. However, 72 hr after injection, spontaneous photon emission from the livers was lowered to 37.0 ± 14.9 counts/min/cm2. These observations were closely correlated with those of the activities of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT), which were released in the course of hepatocellular death. Delayed luminescence also showed clear distinction in its time course of relaxation between the carbon tetrachloride-treated and control groups. On the basis of these observations, we suggest that these photon emissions are involved in the process of death and/or proliferation of liver cells after acute exposure to carbon tetrachloride with sublethal doses. Further, these photon emissions might be originated from the process of lipid peroxidation and consequent radical scavenging by antioxidant enzymes in injured liver tissue. This model study might provide a basis for the analysis of hepatotoxicant induced liver injury and repair by means of measurements of the photon emissions.
We investigated the effect of consumption of a catechin-containing drink on body fat level and its safety in healthy adults. The beverage (250 ml/bottle) contained 215.3 mg of tea catechins mostly possessing a galloyl moiety, which included (-)-epigallocatechin gallate 74.6 mg, (-)-epicatechin gallate 34.1 mg, (-)-gallocatechin gallate 77.8 mg, (-)-catechin gallate 24.5 mg. We conducted a double-blind study with three parallel groups. Healthy subjects (98 men and 97 women) aged from 20 to 65 years old with 22.5 < body mass index (BMI) ≤ 30 kg/m2 were assigned to consume 3 bottles of placebo drink (control group), 2 bottles of catechin-containing drink and 1 bottle of placebo drink (low-dose group), or 3 bottles of catechin-containing drink (high-dose group), per day at mealtimes for 12 week (daily consumption of catechins was 41.1, 444.3 or 665.9 mg respectively). Compared to the value at 0 week, consumption of two or three bottles of catechin-containing drink results in significant decrease in body weight and BMI at 8 and 12 or 4, 8 and 12 week, respectively. Body weight and BMI was significantly decreased in both catechin groups compared with the control group from 4 to 12 week. The measurements of abdominal fat areas indicated significant reduction of total fat area and visceral fat area in both catechin groups compared with the control group at 12 week. Thus our present observations suggest that consumption of a catechin-containing drink may be useful for the prevention of obesity-related disorders.
Nichin-to, a traditional Chinese herbal (Kampo) medicine, has been used to treat nausea and vomiting. Most of traditional herbal medicines are prepared from several different herbs. For example, Nichin-to is a combination of five herbs: Pinelliae Tuber, Zingiberis Rhizoma, Poria, Glycyrrhizae Radix and Aurantii Nobilis Pericarpium. Thus, to determine the exact pharmacological mechanisms of Chinese herbal medicines is very difficult. However, the pharmacological effects of some Chinese herbal medicines can be elucidated from the changes in plasma levels of neuropeptides. In this study, we investigated the effects of Nichin-to on the plasma levels of gut-regulated peptides [gastrin, somatostatin, motilin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and substance P] in healthy human subjects. A single oral administration of Nichin-to caused significant (p < 0.05) increases in plasma levels of gastrin-, somatostatin-, VIP-, motilin-, CGRP- and substance P-immunoreactive substance (IS), compared with placebo group. In conclusion, these results might indicate that the pharmacological action of Nichin-to is closely related to changes in these peptide levels in human plasma, and we hypothesize that the pharmacological effect of Nichin-to might be due to improvement of digestion, and accelerating the rate of gastric emptying and intestinal propulsion.
In order to determine the level of estrogenic substances in river water and to evaluate the degradation of estrogen by aquatic bacteria, three in vitro assays, E-Screen, Ishikawa cell-alkaline phosphatase (Ishikawa cell-ALP) assay and yeast estrogen screen (YES) assay were used. Water samples were collected throughout one year at upstream, midstream and downstream locations on the Muko River, Hyogo Prefecture, Japan. Estrogenic substances in the water were extracted by solid phase extraction using Sep-pak C18 cartridges. The levels of estrogenic substances in river water changed daily, weekly and monthly. The highest 17β-estradiol equivalent (E2 equivalent) was obtained as 32.9 ng/l at the midstream in July of 2002. Although some differences in E2 equivalent were observed in some water samples between the E-Screen and Ishikawa cell-ALP assays, the levels measured by these assays were generally similar and ranged from not detected (ND) to 32.9 ng/l. E2 equivalent levels assayed by YES were low or below the detection limit. Degradability of estrogen by aquatic bacteria was investigated in the summer and winter. E2 and estrone (E1) were degraded completely within five days in the summer, and within seven days in winter. Bacterial degradation of a synthetic estrogen, 17α-ethynylestradiol (EE2), was much lower compared to that of E2 or E1.
Female Sprague-Dawley rats were given a single dose of tamoxifen (20 mg/kg body weight) by gavage or the same dose at 24-hr intervals for 2, 12, or 52 weeks, and the altered expression of cyclin-dependent kinase-interacting protein p21 (p21), tumor suppression protein p53, and the placental form of glutathione S-transferase (GST-P) in the liver was comparatively examined during the process of tamoxifen-induced hepatocarcinogenesis. The development of hepatocellular carcinoma was histopathologically observed only in rats administered tamoxifen for 52 weeks, but not in any other experimental groups. Significant increases in levels of the mRNA and protein of p21 were first observed in rats administered tamoxifen for 2 weeks, and the levels increased with further long-term treatment. Immunohistochemical analyses of p21 and GST-P in the liver of rats administered tamoxifen for 12 and 52 weeks revealed that the localization of p21-positive cells did not necessarily coincide with that of GST-P-positive cells. In the 52-week group, p21-positive cells, rather than GST-P-positive cells, were observed preferentially in the region consisting of histopathologically malignant cells. The present study demonstrated that during the process of tamoxifen-induced hepatocarcinogenesis, expression levels of the mRNA and protein of p21 were increased. The significance of the increased expression of p21 during hepatocarcinogenesis is discussed.
Changes in circulating biochemical markers of bone metabolism in aged individuals with the intake of fermented soybean (natto), which was made from isoflavone-rich soybean, supplemented with zinc were investigated. Sixty-three volunteers (31 men and 32 women) were divided into four groups of 15 or 16 male volunteers and 16 or 16 female volunteers, and each group was sequentially given natto (40-g pack) containing two different levels of zinc once a day for 4 or 8 weeks as follows: either regular natto with naturally occuring isoflavone 35.0 mg, zinc 0.8 mg and calcium 51.4 mg or supplemented natto containing isoflavone 35.0 mg, zinc 3.6 mg, and calcium 60.0 mg. As serum bone markers, bone-specific alkaline phosphatase, γ-carboxylated osteocalcin, bone tartrate-resistant acid phosphatase (TRAP), and N-telopeptide of type I collagen were assayed. The intake of regular natto for 4 or 8 weeks in men or women persons caused a significant increase in γ-carboxylated osteocalcin, a marker of bone formation, and a significant decrease in serum bone N-telopeptide of type I collagen, a marker of bone resorption, as compared with the value before intake. Moreover, the intake of zinc-supplemented natto for 8 weeks in men or women caused a significant increase in serum bone-specific alkaline phosphatase activity and γ-carboxylated osteocalcin concentration and a significant decrease in serum bone TRAP activity and N-telopeptide of type I collagen, as compared with the values with the intake of regular natto. This study suggests that the intake of regular natto with isoflavone-rich soybean has a stimulatory effect on bone formation and an inhibitory effect on bone resorption in aged individuals, and that the effect is enhanced by supplementation with zinc.
Polymerase chain reaction (PCR) primers were prepared to amplify the DNA fragment between the genomic DNA sequence adjacent to the 5′-integration site of Roundup Ready® (RR) soybeans neighboring the transgene and the parts of the coding region of the transgene, together with the primer set for the internal host gene, the α' subunit of β-conglycinin storage protein gene (Cong gene). Using the primers for the transgene and Cong gene, the DNA fragments were amplified from the individual genomic DNAs prepared from 72 samples of RR soybean isolated from imported soybean seeds labeled “not segregated.” Although the frequency of alterations of the nucleotide sequences in both the transgene and Cong gene were almost the same, the mutations that caused alterations to the amino acid sequence were more highly repressed in the transgene than in the Cong gene. In the nucleotide sequence upstream of the coding region of the transgene, the number of alterations of the nucleotide in the proximal promoter region was smaller than that in the further upstream region, suggesting that the mutants missing or being weak glyphosate-tolerance by an alteration of the critical nucleotide sequences in the promoter or coding region might be discarded artificially. It is supposed that the selective bias on the transgene might be extremely high, which indicates that the nucleotide sequence of the transgene might be stable and maintained in inbred RR soybean lines.
We investigated the influences (cell toxicity, endocrine disrupting action, etc.) of polyaromatic hydrocarbons (PAHs) and heavy metals on the human thyroid gland by using a cultured thyroid cancer cell (8505C). Among the six PAHs tested (anthracene, benzo[a]anthracene, benzo[a]pyrene, benzo[k]fluoranthene, chrysene and pyrene), anthracene did not show any effect, but cell proliferation was enhanced by benzo[a]anthracene, benzo[a]pyrene and benzo[k]fluoranthene. Benzo[a]pyrene had an especially marked effect. On the other hand, cell toxicity was exhibited in four (cadmium, copper, nickel and zinc) of the twelve metals tested (aluminum, cadmium, calcium, copper, lead, magnesium, manganese, nickel, tin, zinc, selenate and selenite), and in particular, the influence of cadmium was remarkable. It was found that the toxicity of cadmium was decreased by the addition of high concentrations of either calcium or selenite.
We investigated sex difference in the influence of dietary protein deficiency on the fate of methylmercury (MeHg) using both sexes of C57BL/6N mice and Wistar rats to determine the universality of the influence. One day after oral administration of MeHg (20 μmol/kg), regardless of sex and species, urinary Hg excretion was suppressed by dietary protein deficiency, whereas fecal excretion was not affected. At that time, tissue Hg concentrations in both sexes of the specified species were similarly influenced by dietary protein deficiency except for the gonads, although the influence on Hg concentration in each tissue was different between species. Regardless of sex, dietary protein deficiency resulted in the following alterations: in mice, the brain Hg concentration increased but the concentrations in the liver, kidney, blood and plasma were not affected, and in rats, Hg concentrations in the liver and blood increased but the renal concentration decreased with similar concentrations in the plasma and brain. Hg concentration in the testes was enhanced in mice but suppressed in rats by dietary protein deficiency, whereas that in the ovary was not affected in either species, suggesting that Hg accumulation in the gonads would be more changeable in males than in females by dietary protein deficiency. These results suggest that, regardless of sex, dietary protein deficiency similarly influences the fate of MeHg, except for the gonads. It is also suggested that a decrease in urinary excretion of MeHg by dietary protein deficiency might be universal.
Phytoestrogens and organochlorine pesticides in the diet of laboratory animals are a possible source of interference in bioassays that assess estrogenic activity. In the present study, we investigated the levels of dietary phytoestrogens, organochlorine pesticides and the estrogenic activity of various diets for an experimental fish and discuss the potential contribution of these substances to estrogenic activity, in comparison with those used in previous studies. After hydrolysis with β-glucuronidase, genistein and daidzein were detected in all of the diets, and there were no significant differences in the contents of these substances among present and previous investigations. In addition, organochlorine pesticides, such as hexachlorobenzene (HCB), β-benzene hexachloride (β-BHC), γ-BHC, trans-nonachlor, and/or endrin, were detected in most fish diets. All of these diets exhibited higher levels of activation of β estrogen receptors than with α estrogen receptors in an in vitro yeast-based bioassay. These results indicate that phytoestrogens, such as genistein and daidzein, were the main substances contributing to the estrogenic activity of the diet. Moreover, some diets may exert estrogenic activity in in vivo tests, indicating the necessity for more careful selection of the feeding diet and measurement of estrogenic substances when performing routine screening assays for endocrine-disrupting chemicals.
Total mercury level in biological samples have often been analyzed using atomic absorption spectroscopy (AAS), following the conversion of all the mercury to atomic mercury vapor. On the other hand, analysis of methylmercury (MeHg) using an electron capture detector-gas chromatography (ECD-GC) has well been established. For ECD-GC analysis, the MeHg in samples must be extracted in toluene as its complex with chloride or dithizone. Here, we attempted to analyze MeHg content in rat tissues by the oxygen combustion-gold amalgamation method using AAS, following toluene extraction and back extraction to an aqueous medium. Since all the processes were carried out in a microtube using a micro homogenizing system, microtube mixer and a micro centrifuge, the time required to prepare 12 samples was as short as 30 min. Recoveries of MeHg added to rat brain, kidney and liver homogenates were 83.6-86.7%. Accordingly, a recovery factor of 0.85 was necessary to calculate MeHg content from the analytically obtained value. Using the present method and the previously established method for inorganic mercury quantification, the sum of methyl and inorganic mercury contents in MeHg-treated and non-treated control rat tissues fitted well the total mercury contents. The present method would be useful to estimate, at least roughly, MeHg content in biological samples using the same instrument as total mercury analysis.
The candidate proteins that are involved in the cyclin-dependent kinase 2 (cdk2) signaling pathway were analyzed by comparing different proteins between dominant negative cdk2 overexpressed and control HeLa cells using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE and MS indicated that stathmin and its monophosphorylated form were induced in etoposide-treated HeLa cells compared to untreated cells and this effect was inhibited by overexpression of dominant negative mutant form of cdk2. Further analysis showed that serine-25 (Ser-25), which comprises the conserved target motif for phosphorylation by mitogen-activated protein kinase (MAPK), was the major phosphorylation site of monophosphorylated form of stathmin. These findings indicate that etoposide-induced expression and phosphorylation at Ser-25 of stathmin might be mediated by activation of the MAPK signaling pathway, which is mediated by the cdk2 activation during the onset of the anticancer agent induced apoptotic events in the cancer cells.
Improvement in dietary habits and regular exercise is considered to be effective in preventing and/or reducing obesity and lifestyle-related diseases. The aim of this study was to analyze the effects of the combination of regular exercise and tea catechins intake on energy expenditure in humans. Fourteen healthy male subjects of 26 to 42 years of age received either a test beverage containing tea catechins or a control beverage without tea catechins for 2 months period; during this period they also engaged in treadmill exercise at a pace of 5 km/hr for 30 min 3 times a week. Energy expenditure in a sedentary condition or during the treadmill exercise was measured after 2 months by indirect colorimetry. Fat utilization for energy expenditure under both sedentary and exercising conditions was significantly increased by the combination of regular exercise and tea catechins intake compared to that by exercise alone.
The efficiency of human immunodeficiency virus type-1 (HIV-1) infection in GHOST/CXCR4 cell was controlled by the frequency of virus access, which was limited by random Brownian motion. Prolonged exposure of cell to virus increased the number of infection. Virus migrated to cell, continuously, during exposure period. Virus adsorption amount increased kinetically. It was confirmed by measurement of accumulated provirus DNA sum that the amount of virus entry depended on exposure time. Increment of virus adsorption amount and the number of infection followed to the theoretical manner that virus adsorption dynamics was regulated by random Brownian motion. This observation says that infectivity of lentivirus vector (HIV-1 based) increases by exposure time dependent way. This phenomenon is applicable to enhancing the efficiency of gene transduction by lentivirus vector.
Transcription of the heat shock protein 70 (hsp70) gene is induced by heavy metals including Cd and Zn, probably through the interaction between the heat shock elements (HSE) and heat shock factor 1 (HSF1) binding to it. We studied the mechanism of this transcriptional activation by means of electrophoretic mobility shift assay (EMSA) and transient transfection assay. In HeLa cells, the DNA-binding activity of HSF1 was activated by Zn in a concentration-dependent manner similar to that for hsp70 gene expression, suggesting the direct contribution of HSF1 to the metal-induced transcriptional activation. To facilitate the analysis of the metal-regulatory mechanism, we attempted to establish a system that can reproduce the metal activation of overexpressed recombinant HSF1. In cells transfected with an HSF1 expression vector, strong HSE-binding activity was detected in EMSA, and reporter gene expression driven by the hsp70 gene promoter was markedly increased. However, no Zn response was observed in either assay. The overexpressed HSF1 appeared to cause the constitutive activation of reporter expression, which is an intriguing feature that might reflect an aspect of the hsp70 gene regulation.
The long-term ingestion of tea catechins has been reported to reduce body fat. The aim of this study was to investigate the effect of the long-term ingestion of tea catechins on postprandial energy expenditure and dietary fat oxidation. Twelve healthy men aged 27-48 years participated in the study. The subjects consumed 350 ml of a test beverage/day that contained either a high dose of catechin (592.9 mg) or a low dose of catechin (77.7 mg) for a period of 12 weeks. Respiratory analyses were conducted before and at 4, 8, and 12 weeks during the test period, in which oxygen consumption and the excretion of 13CO2 were monitored over 8 hr after a single ingestion of a test meal containing 13C labeled triglyceride. The excretion of 13CO2 in the high dose catechin group (the HC group) was significantly increased at 4 and 12 weeks of the test period compared to that for the low dose catechin group (the LC group) (p < 0.05), and this elevation persisted at 8.9% at week 0 to 12.9% at week 12. Dietary induced thermogenesis (DIT), defined as an increased energy expenditure from the fasting baseline for 8 hr after the single ingestion of a test meal, was significantly higher in the HC group at 8 and 12 weeks compared to that in the LC group (p < 0.05) with elevation to 90.3 kcal at week 12 from 51.4 kcal at week 0. In conclusion, enhanced dietary fat oxidation and an increased DIT may play an important role in the mechanism of the anti-obesity effect of tea catechins.
Many DNA-binding transcription factors require coactivators for their function. Some of these coactivators have histone acetyltransferase (HAT) activity, which is important for transcription from chromatin template. We cloned a cDNA encoding the rat homolog of monocytic leukemia zinc finger protein (MOZ), a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and Tip60) acetyltransferase family. Rat MOZ (rnMOZ) encoded 1998 amino acids and was composed of 16 exons. Comparison of the rnMOZ and human MOZ amino acid sequences revealed 89% identity over the whole sequence and 100% identity in the MYST region, which is essential for HAT activity. Further, we identified physical interaction between rnMOZ and basic leucine zipper (bZIP)-type DNA-binding proteins, including c-Jun and CCAAT/enhancer binding proteins. This finding suggests that MOZ may function in multiple cellular processes through various bZIP-type transcription factors.
Cetraxate hydrochloride (cetraxate), an antiulcer drug, produces a dose related increase in mucosal blood flow. We have reported that cetraxate increases plasma calcitonin gene-related peptide (CGRP) and substance P in healthy human subjects (J. Pharm. Pharmacol., 56, p. 557, 2004). Cetraxate is rapidly metabolized to tranexamic acid in plasma. We investigated the effect of tranexamic acid on human plasma CGRP, substance P, gastrin and somatostatin. Tranexamic acid at a dose of 500 mg or placebo was orally administered in five healthy male volunteers. The blood samples were taken before and at 20, 40, 60, 90, 120, 180 and 240 min after administrations, followed by the extracting procedure, and submitted to the high sensitive enzyme immunoassay system for CGRP and substance P as previously developed. Single administration of tranexamic acid caused significant increases of plasma CGRP concentration at 60-90 min compared with placebo, but the level-time profile was a little different from that of cetraxate. Tranexamic acid had no significant effect on plasma gastrin, somatostatin and substance P levels compared with placebo. In this study, we thought that the gastroprotective effect of cetraxate might not be due to plasma metabolite, tranexamic acid, but direct stimulation of gastric mucosa.