Organotin compounds have been widely used as agricultural fungicides, rodent repellents, and molluscicides and in antifouling paints for ships and fishing nets. These widespread uses have resulted in the release of increasing amounts of organotins into the environment. In aquatic invertebrates, particularly marine gastropods, organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), induce irreversible sexual abnormality in females which is termed “imposex” at very low concentrations. Although it has been theorized that these compounds act as potential competitive inhibitors of aromatase, which converts androgen to estrogen, and then increase levels of unconverted androgens in gastropods, their effective concentrations for aromatase inhibition are high. In addition to wildlife, organotins may have various undesirable effects on human health. In human ovarian granulosa cells, these compounds suppress aromatase activity at the nanomolar level. Contrary to this, in human choriocarcinoma cells, these compounds markedly enhance estrogen biosynthesis along with the increase of aromatase activity at the same low concentrations. Although there are many reports describing the potential toxicity of organotins, the critical target molecules for the toxicity of organotin compounds remain unclear. New data identify TBT and TPT as nanomolar agonist ligands for retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) γ, which are members of the nuclear receptor superfamily. Here, we review the potential toxicity of organotin compounds via these nuclear receptors in mammals.
Rosa roxburghii Tratt is an herbal medicine with anticancer potential. This study investigated the effects of an ethanol extracts and a triterpene (CiLi triterpene) of Rosa roxburghii on proliferation and differentiation of human hepatoma SMMC-7721 cells and in umbilical cord blood CD34+ hematopoietic progenitor cells. The CiLi triterpene and ethanol extracts inhibited the proliferation of hepatoma cells in a concentration- and time-dependent manner and decreased the release of alpha-fetoprotein from hepatoma cells. Apoptosis was increased only at the highest dose of the ethanol extract in hepatoma cells. The Cili triterpene and ethanol extracts of Rosa roxburghii did not affect the differentiation of cord blood CD34+ cells to granulocytes and monocytes, as evidenced by flow cytometry analysis of CD11b and CD15. Thus the Cili triterpene and ethanol extracts of Rosa roxburghii are effective in the inhibition of human hepatoma SMMC-7721 cell growth, without affecting the differentiation of CD34+ cells.
The Jordanian population has high rate of coronary artery disease (CAD). The potential association between deficiency of vitamin B12, folic acid, and hyperhomocysteinemia in patients with acute myocardial infarction (AMI), where investigated. A case-control study was carried out involving 210 AMI patients (age 35-70 years; 160 men and 50 women) and 100 normal healthy individuals (age 35-70 years; 70 men and 30 women). Fasting venous blood was obtained from patients and controls. Serum was analyzed for vitamin B12 and folic acid using radioassays. The mean serum B12 concentration in AMI patients was found to be significantly lower in controls. The mean serum folate level in patients was also found to be lower than in controls. On the contrary, plasma homocysteine level in AMI patients was higher than that in controls, but not significantly. However, the homocysteine in normal healthy controls was greater than what had been reported in the literature. Vitamin B12 and folate deficiency in AMI patients was significantly higher than in controls. Plasma levels of homocysteine in smokers were also significantly higher in both patients and controls. Additionally, smokers had significantly lower serum folate levels than nonsmokers. Vitamin B12 and folate deficiency in association with hyperhomocysteinemia may be considered as a risk factor for CAD development.
Purpose: Malignant pleural mesothelioma (MPM) is an extremely lethal neoplasm and continues to be an important health problem in communities facing occupational or environmental exposure to asbestos. One of the most significant problems in the treatment of MPM is the lack of a standardized criterion for the evaluation of response to chemotherapy. In this study, differences between the tumor volumes of International Mesothelioma Interest Group (IMIG) stages, chemotherapy response, and patient response times were investigated. Patients and methods: We used the initial tumor volume determinations from patients with MPM with the point-counting technique indicated in the Cavalieri principle of stereologic design. Results: We observed reduction in tumor volumes from tumor treatment until posttreatment. We found that those patients with the shortest period between initial diagnosis of a tumor volume of 200 mm3 or greater had increases in volume of greater than 50 mm3. Conclusion: There is still no standardized evaluation of MPM responses after chemotherapy to chemotherapy using classic criteria. However, our studies on tumor volume continuer.
3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) is a widely abused, psychoactive recreational drug. There are growing evidences that the MDMA neurotoxic profile may be highly dependent on its hepatic metabolism. MDMA metabolism leads to the production of highly reactive derivates, namely catechols, catechol thioethers, and quinones. In this study the electrochemical oxidation-reduction processes of MDMA human metabolites, obtained by chemical synthesis, were evaluated by cyclic voltammetry based on an electrochemical cell with a glassy carbon working electrode. The toxicity of α-methyldopamine (α-MeDA), N-methyl-α-methyldopamine (N-Me-α-MeDA) and 5-(glutathion-S-yl)-α-methyldopamine [5-(GSH)-α-MeDA] to rat cortical neurons was then correlated with their redox potential. The obtained data demonstrated that the lower oxidation potential observed for the catecholic thioether of α-MeDA correlated with the higher toxicity of this adduct. This accounts for the use of voltammetry data in predicting the toxicity of MDMA metabolites.
The present study was aimed at investigating the effects of Abana, an Ayurvedic herbomineral preparation on memory and brain cholinesterase activity in mice. Drug Abana was administered orally in three doses (50, 100 and 200 mg/kg) for fifteen days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing- induced amnesia served as the interoceptive behavioral models. Brain cholinesterase activity was also estimated. Abana (50, 100 and 200 mg/kg, orally (p.o.)) produced a dose-dependent improvement in memory scores of young and aged mice. Furthermore, it reversed the amnesia induced by scopolamine (0.4mg/kg, intraperitoneally (i.p.)) and diazepam (1 mg/kg, i.p.). Interestingly, brain cholinesterase activity was reduced by Abana administered orally for 15 days. It may prove to be a useful remedy for the management of Alzheimer's disease.
Nicotine has been used as a selective marker to evaluate environmental tobacco smoke (ETS). In this study, a simple and precise nicotine measurement method using a solid phase cartridge (Sep-Pak® Plus PS-2) followed by GC-MS analysis was evaluated. Prior to use, the solid phase cartridge was coated with potassium hydroxide (KOH), and indoor air was then passed through it. After the air sampling, nicotine was eluted from the cartridge with 10μg/ml triethylamine/dichloromethane, and the eluent was analyzed by GC-MS. The nicotine recovery from the spiked cartridge was more than 80% for an air sampling time of 12hr, and the method detection limit (MDL) for the air sampling with an air volume of 721 was 0.35μg/m3. When the cartridge was used for indoor air measurement, the nicotine concentrations in the smoking room ranged from 12.9μg/m3 to 86.6μg/m3, which were proportional to the number of smoked cigarettes.
Gabexate (GB), a serine protease inhibitor that is widely used for the treatment of acute pancreatitis and disseminated intravascular coagulation, has been reported to be partly hydrolyzed by human serum albumin. However, other enzymes responsible for GB hydrolysis in human blood remain unclear. In this study, we examined in vitro metabolism of GB with human blood samples. The hydrolytic activities of the plasma and erythrocytes at 100 μM of GB were 167 ± 26 and 151 ± 9 nmol/min/ml blood fraction (mean ± S.D., n = 8), respectively. Kinetic analysis indicated that Vmax and Km values were 1.75 μmol/min/ml blood fraction and 529 μM for the plasma and 10.6 μmol/min/ml blood fraction and 7360 μM for the erythrocytes, respectively. The activity of human plasma was inhibited by ethopropazine, a butyrylcholinesterase inhibitor (27% inhibition at 100 μM). Furthermore, the plasma activity was inhibited by 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB) (40% inhibition at 5000 μM), suggesting the involvement of albumin in the plasma GB hydrolysis. The erythrocyte activity was also decreased by DTNB (56% inhibition at 5000 μM), implying that this activity was dependent on the presence of sulfhydryl group(s), while little or no inhibition of the activity was seen with phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, and BW284C51. Butyrylcholinesterase from human serum showed GB hydrolytic activity with Vmax of 363 nmol/min/mg protein and Km of 263 μM. These results suggest that, in addition to albumin, butyrylcholinesterase and erythrocyte sulfhydryl-dependent enzyme are responsible for GB hydrolysis in human blood.
Doxorubicin is highly effective in treatment for several forms of cancer. However, doxorubicin induces a cumulative and dose dependent cardiomyopathy that has been ascribed to redox-cycling of the molecule on the mitochondrial complex 1 generating in the process of increased oxidative stress. In the search of new potential cardioprotective agents, the present study is directed to explore the effect of ethanolic extract of Nardostachys jatamansi on the mitochondrial and lysosomal damage induced by doxorubicin in rats. Heart mitochondria were isolated from rats treated with doxorubicin (15 mg/kg, ip) a single dose, exhibited depressed rates of state 3 respiration, low respiratory control ratio (RCR), decreased Oxidative Phosphorylation ratio, Adenosine Triphosphate content and cytochromes (c, c1, b, aa3). In addition the doxorubicin given rats showed significant changes in the lysosomal enzymes (Cathepsin-D, Acid phosphatase, β-D-glucoronidase, β-D-galactosidase and β-N-acetyl glucosaminidase) and membrane bound phosphatases. Also myocardial damage, as assessed by ultrastructural changes showed loss of myofibrils, mitochondrial swelling, and cytoplasmic vacuolization. Pretreatment with Nardostachys jatamansi (500 mg/kg body weight orally) for seven days ameliorated the observed abnormalities and significantly prevented the mitochondrial respiration, lysosomal integrity, membrane bound phosphatases and ultrastructural studies in doxorubicin induced rats. These findings suggest that the cardioprotective efficacy of Nardostachys jatamansi could be mediated possibly through its antioxidant effect as well as by the attenuation of the oxidative stress.
The mechanism by which perfluorooctanoic acid (PFOA) is transported in the kidney was studied in rats. We hypothesized that some transporters that are expressed in the basolateral and/or brush border membrane of proximal tubular cells mediate the transport of PFOA. Mannitol infusion, which caused an increase in the urine flow rate, significantly increased the renal clearance (CLR) of PFOA in both male and female rats. Feeding a low-phosphate diet that causes an increase in the expression of rat type II sodium-dependent phosphate transporter (Npt2) reduced the CLR in both male and female rats. These suggest that PFOA is reabsorbed in the proximal tubules, and that a phosphate transporter may be responsible for the renal transport of PFOA. The CLR of PFOA in Eisai hyperbilirubinemic rats that lack multidrug resistance-associated protein 2 (MRP2) was not different from that of the wild type, suggesting that MRP2 is not responsible for the renal transport of PFOA. Three candidate transporters, organic anion-transporting polypeptide 1 (oatp1), Npt2, and organic anion transporter 3 (OAT3) were studied to clarify whether these transporters facilitate [14C]PFOA transport in functional studies in Xenopus laevis oocytes. Both oatp1 and OAT3 facilitated [14C]PFOA transport while Npt2 did not. These results suggest that both oatp1 and OAT3 mediate, at least in part, the transport of PFOA in the proximal tubules of rat kidney.
Metabolic syndrome (MS) is a combination of glucose and lipid abnormalities and associated with cardiac and cerebral events and the likelihood of inducible myocardial ischemia and stroke. As MS is partly a result of living and behavioral patterns, we assessed whether there exists some relationship between MS morbidity and the lifestyle of urban citizens. We evaluated 836 patients in the age range from 35 to 97 years. All participants were divided into five groups: MS group, essential hypertension group, type 2 diabetes group, essential hypertension combined with type 2 diabetes group and control group. The baseline data and other serum indices were collected. A specifically designed questionnaire was used to inquire about the current situation of each patient. Finally, we assess the influence of various factors on MS patients after grouping. Body mass index and waistline in the MS group were significantly greater than in other groups. Smoking, amount of alcohol consumption, and moderate physical activity were several crucial factors in the MS group compared with the control group. The intake of fatty and pickled food in the MS group was also higher compared with those in other groups. Average time of physical exercise decreased in the order control group, essential hypertension group, and MS group (p < 0.05 or p < 0.01). We conclude that among urban middle-aged and older patients in Shanghai, MS patients are overweight, have severe dyslipidemia, smoke and consume alcohol, eat more fatty food, and perform less physical exercise, which point out the importance of prevention, corresponding therapeutic lifestyle changes, and medication.
Since residual malathion in wheat kernels is shown to be enzymatically decomposed during sample preparation using the Japanese official method for pesticide analysis, the decomposition products were identified by semi-micro radio liquid chromatography (LC). The reaction mixture of the supernatant of wheat kernel homogenate incubated with [14C] malathion for 0-8 hr was fractionated, and the radioactive decomposition products in the fractions were identified by comparison with the retention time of fifteen reference standards. Twelve of these products occurring in the environment, diethyl fumarate, diethyl maleate, diethyl malate and diethyl succinate, and their hydrolysate and desmethyl malathion dicarboxylic acid were not detected in the reaction mixture, indicating no contribution of organophosphorus hydrolase or methyl transferase. A trace amount of desmethyl malathion was observed, however, this seemed to be non-enzymatically produced. Malathion monocarboxylic acid and malathion dicarboxylic acid were identified as the major products by the LC condition with and without an ion pair reagent, respectively. The half life of malathion decomposition was 2.1 hr, and the reaction time course of these products demonstrated that malathion was decomposed to malathion monocarboxylic acid followed by malathion dicarboxylic acid. These results suggested that residual malathion in wheat kernels was mainly hydrolyzed to malathion carboxylic acids by wheat carboxylesterase during the sample preparation.
The sorption isotherms of polycyclic aromatic hydrocarbons (PAHs) by insoluble dietary fiber (IDF) were measured in artificial gastric juice (AGJ) and artificial intestinal juice (AIJ) at 37°C and then the sorption behavior of IDF was examined. Benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene were used. It was suggested that the uptake of PAHs by carboxymethyle cellulose (CMC), agar, and IDF from powdered young barley leaves (YBL) involved not single sorption behavior, but complex sorption behavior. YBL had an extraordinarily high sorption capacity (60.7-147.3 nmol/g in AGJ and 76.7-162.7 nmol/g in AIJ), as compared with CMC (1.5-3.6 nmol/g in AGJ and 1.1-2.7 nmol/g in AIJ) and agar (0.1-0.4 nmol/g in AGJ and 0.3-0.7 nmol/g in AIJ) at a residual concentration of 5.0 nM. The sorption of PAHs in AGJ and the desorption of PAHs from IDF in both AGJ and AIJ indicate that the sorbed PAH molecules are held firmly by IDF while it passes through the digestive tract in vivo. From the results on sorption capacity and the removability of PAHs from IDF, YBL would be expected to be more useful than CMC and agar.
To investigate the contents of radionuclides in foods marketed in Japan and their daily intakes and exposure doses in adults, we performed market-basket studies concerning radionuclide intakes. The study period was 2003-2005, and the studies were performed in 13 cities in Japan. Foods including drinking water were divided into 14 food groups, and samples were prepared by common cooking procedures. γ-ray emitting nuclides (an artificial radionuclide, radioactive Cs, and natural radionuclides, 40K and U series such as 214Bi, and 212Pb, and Th series) were measured in each food group, and artificial radionuclides, 90Sr and 238U, were measured in a mixed sample of 13 food groups excluding drinking water. The daily intakes in adults were calculated from the concentrations of the radionuclides and mean daily consumption of foods and drinking water. The daily 137Cs and 40K intakes (mBq/person·day) in the 13 cities were 12.5-<79.7 and 57309-95746, respectively. The 90Sr intake from the food groups excluding drinking water was 20.8-53.6, with a mean of 39.2 (mBq/person·day) (deviation of the mean: 23%). Similarly, the daily 238U intake was 5.9-31.1, with a mean of 12.6 (mBq/person·day) (deviation: 60%), showing a more than 5-fold difference between the minimum and maximum values, and there were regional differences. Since the contents of the U series, such as 214Bi and 212Pb, and Th series were lower than the lower detection limits in many samples, their daily intakes were not calculated. Regarding the daily intake of 137Cs from each food group, the intakes from fish and shellfish, milk, meat/eggs, and mushrooms/seaweed tended to be higher. The daily 40K intake from each food group varied among the areas, but the total intake from the 14 food groups was similar in all 13 cities. 40K from these foods accounted for most of the annual effective dose (μSv/person·year) of γ-ray emitting nuclides, and the doses of 40K, 90Sr, and 238U were 130-217, 0.21-0.55, and 0.10-0.51, respectively.
Sick-building syndrome (SBS) symptoms associated with indoor air volatile organic compounds (VOCs) in new or newly remodeled houses have been increasingly highlighted, and are known as “sick house syndrome” in Japan. In the course of the investigation of SBS patients, we found two sensitive patients who complained of severe symptoms and had elevated serum levels of p-dichlorobenzene and 2-ethyl-1-hexanol. One patient was a housewife, who complained of various symptoms such as headache, itching eyes, nasal irritation, and night sweats and had a high serum level of p-dichlorobenzene (25.4 ng/ml). She showed some improvement of symptoms in association with the gradual decrease in p-dichlorobenzene concentrations in both her bedroom and her serum. The other patient was a female professor who had experienced mainly respiratory symptoms, such as nonproductive cough, throat irritation, etc. when she entered her office, classrooms, and a faculty meeting room in a university building. Her serum 2-ethyl-1-hexanol concentration was 4.6 ng/ml, which was more than 7.7-fold higher than that in four other patients with other onsets. The elevation of her serum 2-ethyl-1-hexanol level was assumed to be due to daily exposure in the university building.
Genotoxicity of furfuryl alcohol and 2-furyl methyl ketone is evaluated by sister chromatid exchange analysis (SCEs) in mouse bone marrow system using standard technique. Three doses of the compounds ranging from 1000-4000 ppm were given by oral gauvage to experimental animals for one day in single dose series and for five consecutive days in multiple dose series to simulate a human situation. 5-Bromodeoxyuridine (5-Brdu) was intraperitoneally injected at hourly intervals for 6 hr at a concentration of 0.04mg/g body weight. In both single and multiple dose series the animals were exposed to 5-Brdu for 26 hr and were sacrificed after 12, 24 and 48 hr following last feeding. Control animals received distilled water and same concentration of Brdu. Bone marrow slides were prepared and stained as per standard procedure. 100 metaphase spreads in second mitotic division were scored from each dose and period and subjected to statistical analysis. There was significant induction of SCEs in both single and multiple dose series with both the compounds. It was found to be dose dependant and the period dependancy showed a decline after 24 hr.
The quantity of L-malate was determined using apparatus comprised of a reactor with immobilized malate dehydrogenase (MDH) and aspartate aminotransferase (AST) in a flow line. NADH formed by an enzymatic reaction was fluorometrically detected. The optimal concentration of NAD+ in the carrier containing 0.1M glutamate was determined. The maximum peak areas due to NADH were observed at pH 8.0 when the pH of the carrier consisting of Tris buffer ranged from 7.0 to 8.5. Various buffer types were also examined as carrier media at pH 8.0 and Tris buffer showed the maximum peak area. When the carrier composed of Tris buffer (0.1M, pH 8.0) was used, the calibration curve for malate was linear in the range of 0.05-50μM (r = 1.000). The detection limit (S/N = 3) was 0.03μM. Relative standard deviations of the peak area at 1μM and 10μM were 1.5% (n = 7) and 0.36% (n = 7), respectively. Thirty samples of malate (10μM) were analyzed for 1 hr. This method was applied to the analysis of malate in several beverages, and malate content determined by this method agreed with that determined by a commercially available test-kit method.
We measured the concentration of carbon monoxide (CO) gas in exhaled breath and the level of stress in students to evaluate their lifestyle and mental health for the annual medical checkup at our University. 993 students were examined for CO by gas analysis device and 445 selected randomly from them for stress levels by a Stressometer. CO concentration in breath is markedly higher in the case of smokers and slightly higher in non-smokers who are exposed to passive smoking. Students with a tremor of the nervous system at rest (TNR) higher than 70 in a Stressometer were found in 13.0%, and in non-smoking female students there was a significant correlation between stress levels and CO concentration in the breath which is produced in the cells by stress-induced heme oxygenase-1. The results of the present study suggest that measuring CO gas may be a convenient way to evaluate lifestyle and stress levels in students.
The reproductive functions were evaluated by epididymal sperm counts, motility, fertility rate, reproductive organ weights, biochemistry and histological examination of testes in vanadyl sulphate treated adult male Wistar rats. Oral administration of vanadyl sulphate (100mg/kg b.wt./day) for 60 days caused a decrease (p < 0.05) in the weights of testes and accessory reproductive organs. Cauda epididymal sperm analysis exhibited a significant decline in the number (p < 0.01) and motility (p < 0.001). Atrophy of seminiferous tubules was observed in histopathological examination. The diameter of seminiferous tubules and Leydig cells nuclei were reduced. Biochemical analysis of marker parameters indicated alteration in biochemical milieu of the genital organs. The mating tests with untreated females revealed a decrease in pregnancy rate and mean number of the pups delivered. As such present investigation indicate an adverse effect of vanadyl sulphate on male reproductive functions.
Stress is a term that generally has a negative connotation, which results in immune dysfunction. In this study, immunomodulatory effect of Triphala (equal proportion of Terminalia chebula, Terminalia bellerica and Emblica officinalis) during noise-stress in male albino rats was evaluated by analyzing the antibody titer, cytokines IL-2-Interleukin (2), IL-4 and IFN-Interferon (gamma) and Pan T, CD4+/CD8+ lymphocyte phenotype in spleen. Four groups of rat were employed namely control, Triphala (1 g/kg body weight), noise-stress (100 dB/4 hr/15 days), Triphala + noise-stress and rats were immunized with sheep red blood cells (5 × 109 cells/ml). Results indicate that noise-stress induced elevation in the serum antibody titer and IL-4 levels associated with decreased IL-2, IFN-gamma, and reduction in Pan T, CD4+/CD8+ lymphocyte phenotype in spleen were significantly prevented in Triphala treated noise-stress exposed group. This study showed the immunomodulatory effect of Triphala during noise-stress and suggests its therapeutic usefulness.
TR-TBT 18d-1 is a syncytiotrophoblast cell line established from placenta of the transgenic rat harboring temperature-sensitive simian virus 40 large Tantigen (Tg-rat). Previously we have reported high level expressions of drug metabolizing enzymes in the TR-TBT cells. To elucidate the ability of metabolizing xenobiotics in the TR-TBT cells, we measured the metabolism of bisphenol A (BPA) as a model compound in the TR-TBT 18d-1 cells. It was found that BPA was metabolized and secreted as a monoglucuronide conjugate in a manner proportional to the incubation time and the BPA concentration. To elucidate the possible effect of green tea consumption on the placental metabolism, we investigated the effect of green tea on the metabolism of BPA in the TR-TBT cells. Green tea inhibited the conjugation reaction of BPA at the low concentration (IC50=5%), however, epigallocathechin gallate (EGCG) showed only weak inhibition, suggesting another active component existence. These results suggest that TR-TBT cells are useful for the model system of rat syncytiotrophoblasts which act as a barrier to protect fetus from harmful xenobiotics.
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