Effects of mercury release from amalgam dental restorations during cremation on soil mercury levels of three New Zealand crematoria.
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Dental Amalgam↗
Biomedical subjects
N D Kim
Publications and source records attributed to N D Kim.
Heavy metals and organic hydrocarbons in sediments from the Waikareao Estuary, Tauranga Harbour, New Zealand.
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Alkanes↗
Determination of a new antiulcer agent, eupatilin, in rat plasma, bile, urine, and liver homogenate by high-performance liquid chromatography.
A high-performance liquid chromatographic method was developed for the determination of a new antiulcer agent, eupatilin, in rat plasma, urine, bile, and liver homogenate. The method involved deproteinization of biological sample with the same volume of acetonitrile. A 100 microl aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was ammonium acetate buffer (1% ammonium acetate and 0.5% acetic acid) - acetonitrile (58:42, v/v) and the flow rate was 1.0 ml/min. The column effluent was monitored by a ultraviolet detector set at 350 nm. The retention time for eupatilin was approximately 6.5 min. The detection limits for eupatilin in rat plasma, urine, bile, and liver homogenate were 50, 50, 100, and 100 ng/ml, respectively. The coefficients of variation of the assay were generally low (below 7.46%) for rat plasma, urine, bile, and liver homogenate. No interferences from endogenous substances were observed.
Animals↗
The response of the Intoxilyzer 5000 to five potential interfering substances.
A study was conducted of potential vapor phase interferents which could be present on human breath and also be capable of inducing a false-positive response for ethanol on the evidential infrared-based breath testing device, the Intoxilyzer-5000. This involved preparation and validation of a range of vapor standards, which were introduced to the instrument using a dynamic flow double-bubbler system. Potential interferents were chosen on the basis of both their infrared signatures and their general availability, and included toluene, m-xylene, o-xylene, methanol and isopropanol. All compounds tested were found to be capable of inducing false-positive readings for ethanol in a highly reproducible manner, as a result of which it has been possible to derive precise least-squares equations describing the ethanol readout expected for any given blood concentration of toluene, m-xylene, o-xylene, methanol and isopropanol. The likelihood of an interference compromising the integrity of the analysis is related to both the toxicological significance and prevalence of a given blood concentration of each solvent, and the point at which the instrumental interference light is triggered in each case.
2-Propanol↗
Inhibitory effects of retinoids on development of squamous metaplasia in rat mammary epithelial organoids cultured in Matrigel.
Squamous metaplasia (SQM) developed in cultures of rat mammary organoids in reconstituted basement membrane, Matrigel, under either a complete hormone medium (CHM) or a serum-free mammary epithelium growth medium (MEGM). Organoids cultured in CHM gave rise to fewer such SQM (approximately 5%) than those in MEGM (approximately 16%). Formation of SQM was completely suppressed when retinoids were added to CHM. However, a few SQM were still observed in cultures in MEGM with added retinoids. Addition of 5% fetal bovine serum suppressed development of SQM cultured in MEGM. Delayed addition of retinoids also inhibited further development of SQM. Development of SQM from mammary epithelial cells is not common, and regulatory molecules other than retinoids apparently are involved in their formation and prevention.
Animals↗
Suppression of rat hepatic cytochrome P450 2E1 expression by isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl] acetate (YH439), an experimental hepatoprotectant: protective role against hepatic injury.
The expression of cytochromes P450 2E1, P450 2B and P450 1A was examined in rat hepatic tissue in response to YH439, an experimental hepatoprotective agent. P450 2E1 metabolic activities relatively specific for P450 2E1 were decreased up to 57% of control activities in the hepatic microsomes prepared from rats treated with YH439 for 3 days. Immunoblot analyses showed that P450 2E1 levels were decreased below the limit of detectability in hepatic microsomes prepared from YH439-treated rats. YH439 at doses from 25 to 100 mg/kg completely suppressed isoniazid-inducible P450 2E1 levels as monitored by both metabolic activities and immunoblot analysis. RNA hybridization analysis revealed that P450 2E1 mRNA levels failed to change after YH439 treatment. These results demonstrate the YH439 effectively suppresses P450 2E1 expression in the absence of transcriptional inactivation. YH439 failed to affect P450 2B1/2 expression, whereas this agent enhanced the hepatic P450 1A1/2 levels. The hepatoprotective effects of YH439 were also examined. Animals treated with CCl4 and ethanol for 9 weeks showed hepatic injury as demonstrated by 2.5- and 2-fold increases in serum alanine aminotransferase and alkaline phosphatase activities, respectively. Concomitant YH439 treatment resulted in a significant protective effect against the experimental hepatic injury. The toxicant-induced elevation in hepatic hydroxyproline level was completely blocked by YH439 treatment. These data indicate that YH439 suppresses the expression of P450 2E1 and protects the liver against chemical-induced hepatic injury and that the selective modulation of detoxifying enzymes by YH439 may contribute to the protection of liver from xenobiotic-induced intoxication.
Animals↗
Individual RNA recognition motifs of TIA-1 and TIAR have different RNA binding specificities.
TIA-1 and TIAR are two closely related RNA recognition motif (RRM) proteins which possess three RRM-type RNA binding domains (RRMs 1, 2, and 3). Although both proteins have been implicated as effectors of apoptotic cell death, the specific functions of TIA-1 and TIAR are not known. We have performed in vitro selection/amplification from pools of random RNA sequences to identify RNAs to which TIA-1 and TIAR bind with high affinity. Both proteins selected RNAs containing one or several short stretches of uridylate residues suggesting that the two proteins have similar RNA binding specificities. Replacement of the uridylate stretch with an equal number of cytidine residues eliminates the protein-RNA interaction. Mutational analysis indicates that, for both TIA-1 and TIAR, it is the second RNA binding domain (RRM 2) which mediates the specific binding to uridylate-rich RNAs. Although RRM 2 is both necessary and sufficient for this interaction, the affinity for the selected RNA (as determined by filter binding assays) does increase when the second domain of TIAR is expressed together with the first and third domains (Kd = 2 x 10(-8) M) rather than alone (Kd = 5 x 10(-8) M). Although RRM 3 (of either TIA-1 or TIAR) does not interact with the uridylate-rich sequences selected by the full-length proteins, it is a bona fide RNA binding domain capable of affinity-precipitating a population of cellular RNAs ranging in size from 0.5 to 5 kilobases. In contrast, RRM 1 does not affinity-precipitate cellular RNA. The inability of RRM 1 to interact with RNA may be due to the presence of negatively charged amino acids within the RNP 1 octamer.
Base Sequence↗
Metabolic changes of acetaminophen after intravenous administration to rats pretreated with a hepatoprotective agent, YH-439.
The metabolic changes of acetaminophen (AAP) were investigated after the intravenous (iv) administration of AAP, 300 mg per kg body weight, to the control rats (n = 7) and rats pretreated with a new hepatoprotective agent, YH-439 (200 mg per kg body weight, orally administered for 3 consecutive days, n = 7). After iv administration of AAP, the AUC of AAP was significantly smaller and both the CL and CLNR of AAP were significantly faster in the YH-439 treated rats. The CLR of AAP-glucuronide and the partial clearance of both AAP-glucuronide and AAP-sulfate were significantly faster in the YH-439 pretreated rats. The percentages of iv dose excreted in 6 hr bile as AAP-glucuronide, AAP-glutathione, and AAP-cysteine-expressed in terms of AAP-significantly increased in the YH-439 pretreated rats. The above data suggest that the metabolism of AAP increases by pretreatment with YH-439, and the mechanism for the hepatoprotective effect of YH-439 appears to be due, at least in part, to the increased detoxification by the enhanced glucuronidation, and cysteine and glutathione conjugation of AAP.
Acetaminophen↗
Effect of a hepatoprotective agent, YH-439, on the pharmacokinetics of furosemide and azosemide in rats.
The effect of YH-439 pretreatment on the pharmacokinetics of furosemide and azosemide was investigated after intravenous (iv) administration of furosemide, 6 mg per whole body weight, and azosemide, 10 mg per kg body weight, to rats pretreated with 3 consecutive daily oral administration of YH-439, 200 mg per kg body weight. The nonrenal clearance of furosemide (2.20 versus 3.53 ml/min/kg) increased significantly, and the 24 h-urinary excretion of furosemide (both the amount and percentages of iv dose) decreased significantly in the YH-439 treated rats when compared with those in the control rats. The results were unexpected since the metabolism of furosemide increased by pretreatment with phenobarbital (CYP2B inducer) and YH-439 pretreatment failed to affect CYP2B expression. The increased metabolism of furosemide by pretreatment with YH-439 could be due to other enzyme(s) induced by pretreatment with YH-439. Pharmacokinetic parameters of azosemide were not significantly different between the two groups of rats except t(1/2), MRT, and V(ss). The results were unexpected since azosemide metabolism increased with 3-methylchloranthane (3-MC, CYP1A inducer) and YH-439 pretreatment increased CYP1A expression. Above data indicate that the expression of CYP1A by treatment with YH-439 was not considerable when compared with that with 3-MC.
Animals↗
Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta.
The vasoactive effects of several ginsenosides, purified from Panax ginseng, were tested in the rat aorta. Ginsenosides from the protopanaxatriol group and its purified ginsenosides Rg1 and Re cause endothelium dependent relaxation which is associated with the formation of cyclic GMP. Both responses to these protopanaxatriol-containing ginsenosides are inhibited by methylene blue, an inhibitor of soluble guanylate cyclase and of nitric oxide synthase. In contrast, ginsenosides from the protopanaxadiol group and its purified ginsenosides Rb1 and Re do not affect vascular tone or production of cyclic GMP in the rat aorta. These findings demonstrate that ginsenosides from the protopanaxatriol group but not from the protopanaxadiol group enhance the release of nitric oxide from endothelial cells and may contribute to the beneficial effect of ginseng on the cardiovascular system.
Animals↗
Evidence for a seasonal fluctuation of arsenic in New Zealand's longest river and the effect of treatment on concentrations in drinking water.
A year-long survey, with samples collected weekly, was conducted to estimate long-term average concentrations of arsenic in treated and untreated drinking water for the city of Hamilton, New Zealand. The average concentration of arsenic in Waikato River water at Hamilton before processing was found to be (32.1 +/- 3.7) microg litre(-1), about three times above the new WHO limit of 10 microg litre(-1). However, full conventional water treatment effects a five-fold reduction in arsenic concentrations in drinking water to a level which meets the new standards of (6.2 +/- 0.8) microg litre(-1). The results of both this study and retrospective analysis of archived data suggest that total arsenic concentrations in the Waikato River are likely to follow a regular seasonal variation, being about 10-25 microg litre(-1) higher in the summer months. Changes in river flow rates have an almost negligible effect on the summer peak and winter trough; it is proposed that most of the variation in total arsenic concentrations may be due to the seasonal conversion of arsenic in the river sediments to more soluble forms.
Journal Article↗
Dietary ginsenosides improve endothelium-dependent relaxation in the thoracic aorta of hypercholesterolemic rabbit.
1. Endothelium-dependent relaxation to acetylcholine was impaired in aortic rings from cholesterol-fed rabbits as compared to rabbits fed with a control diet. 2. The dietary treatment of rabbits with ginsenosides did not affect endothelium-dependent relaxation to acetylcholine but did effect the relaxation in cholesterol-fed rabbits. 3. Dietary treatment of rabbits with ginsenosides did not alter the relaxations to sodium nitroprusside and the contractions to norepinephrine in rings without endothelium from both control and cholesterol-fed rabbits. 4. Ginsenoside feeding had no significant effect on the plasma lipid levels in both control and cholesterol-fed rabbits. 5. These results suggest that dietary supplementation of rabbits with ginsenosides improve the endothelium-dependent relaxation to acetylcholine in the aortic blood vessels in cholesterol-fed rabbits. This beneficial effect of ginsenosides feeding cannot be explained by a facilitation of the cyclic GMP effector pathway in the smooth muscle or by an enhanced cholesterol metabolism but may involve an increased production of nitric oxide by endothelial cells.
Acetylcholine↗
Effects of garlic oil on rat hepatic P4502E1 expression.
1. The effects of garlic oil (GO) on the expression of P4502E1, glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) were assessed by metabolic activities, immunoblot and RNA blot analyses in the rat. 2. p-Nitrophenol (PNP) hydroxylase activity decreased in the hepatic microsomes isolated from rats treated with GO at 200 mg/kg b.w. by 10-30% as compared with control. Pyrazine-inducible P4502E1 expression was decreased by approximately 40% following concomitant treatment of animals with GO at the dose of 200 mg/kg from day 1 to 3 post-treatment, as evidenced by PNP hydroxylase activity. The rates of aniline hydroxylase and NDMA demethylase activities in GO-treated animals were consistent with those of PNP hydroxylase activity. Treatment of animals with 500 mg/kg GO resulted in suppression of P4502E1-mediated catalytic activities, as monitored by both PNP and aniline hydroxylase activities, whereas the effects at the dose of 1000 mg/kg were identical with those at 500 mg/kg b.w. 3. Immunoblot analyses of hepatic microsomes, using an anti-P4502E1 antibody, showed that GO minimally suppressed constitutive P4502E1 expression at 24, 48 and 72 h post-treatment at the daily doses from 200 to 1000 mg/kg b.w., as compared with vehicle-treated animals. Time-dependent pyrazine induction of P4502E1, however, was substantially blocked by concomitant treatment of animals with 200 mg/kg GO to the levels of control. Treatment at the dose of 1000 mg/kg failed to further suppress P4502E1 levels. GO treatment caused no changes in the levels of P4502E1 mRNA, as assessed by slot blot analyses. 4. Cytosol produced from the GO-treated rat showed approximately 40% increases in GST conjugating activity toward 1-chloro-2,4-dinitrobenzene, whereas mEH protein levels were 1.5-2.0-fold greater than control with similar increases in the mRNA levels noted. 5. These results demonstrate that GO suppresses inducible P4502E1 expression more significantly than constitutive expression, and that GO induces GST and mEH expression to a certain extent.
Allyl Compounds↗
Differential expression of microsomal epoxide hydrolase gene by azole heterocycles in rats.
The effects of heterocycles including imidazole (IM), 1,2,4-triazole (TR) and thiazole (TH) on the expression of microsomal epoxide hydrolase (mEH) gene were examined in rats (200 mg/kg body weight/day, i.p.). Hepatic microsomes prepared from rats treated with IM for 3 days failed to exhibit an increase in mEH protein level whereas TR treatment resulted in an approximately 2- to 3-fold elevation in hepatic mEH levels relative to control, as assessed by both SDS-PAGE and immunoblot analyses. In contrast, thiazole-induced hepatic microsomes resulted in a substantial increase in mEH levels (i.e. approximately 5-fold). Slot and northern blot analyses, probed with an mEH cDNA, showed that the hepatic mEH mRNA levels in the animals treated with IM for 3 days were marginally increased by approximately 2-fold, as compared with untreated animals, whereas TR caused an approximately 8-fold increase in hepatic mEH mRNA levels after three consecutive daily treatments. TH treatment resulted in an approximately 22-fold increase in the mEH mRNA levels, demonstrating that TH is the most efficacious among these three azole heterocycles. Because TH was the most effective in increasing hepatic mEH protein and mRNA levels, the agent was chosen for further evaluation. Time course of mEH gene expression at early times after a single treatment with TH was determined and compared with that caused by pyrazine (PZ), a strong mEH inducer. Hepatic mEH mRNA levels were increased approximately 1-, 3-, 20- and 16-fold at 3, 6, 12 and 24 hr, respectively, following TH treatment, relative to control, whereas mEH mRNA levels were elevated approximately 1-, 1-, 22- and 18-fold, respectively, at the same time points after PZ treatment, as monitored by slot RNA hybridization analyses. Northern blot analyses using either total RNA or poly(A)+ RNA fractions exhibited comparable time courses in increasing mEH mRNA levels after TH or PZ treatment with maximal mRNA increases being noted at 12 hr post treatment. Although neither IM or TR failed to affect renal mEH gene expression to a notable extent, TH treatment caused 6- to 8-fold increases in kidney mEH mRNA levels, with a 2-fold increase in mEH protein detected. These results demonstrated that the azole heterocyclic compounds IM, TR and TH differentially induce mEH with TH as the most efficacious azole; and that the changes in mEH levels are primarily associated with increases in mRNA levels.
Animals↗
Malotilate, a hepatoprotectant, suppresses CYP2E1 expression in rats.
The expression of CYP2E1 was examined in hepatic tissue from rats treated with malotilate (MT), a hepatoprotectant. Microsomal p-nitrophenol hydroxylase activity in MT-treated rats was decreased to 66% and 47% of control activity at day 2 and 3 post-treatment. SDS-PAGE and immunoblot analyses of hepatic microsomes prepared from MT-treated rats showed that CYP2E1 levels were decreased below the limit of detectability. In contrast, CYP2B1 levels were increased in MT-treated microsomes, as assessed by immunoblot analyses. MT, however, failed to modulate CYP1A expression. RNA hybridization analysis revealed that CYP2E1 mRNA levels failed to change significantly by day 2 or 3 post-treatment, whereas microsomal epoxide hydrolase mRNA levels were elevated approximately 3-fold at the same time points. These results demonstrate that MT effectively suppresses CYP2E1 expression in the absence of transcriptional inactivation.
Animals↗
The concentrations, distribution and sources of cadmium, copper, lead and zinc in the atmosphere of an urban environment.
The four metals Cd, Cu, Pb and Zn have been measured in residential city air in a relatively small urban environment. The atmospheric concentrations are Cd, 0.516, 0.305; Cu, 12.5, 8.22; Pb, 155, 70.2; and Zn 47.4, 22.4 ng m-3 at two different sites. Except for lead the concentrations are low and more typical of rural areas in more industrialised centres. The concentrations were found to be higher in the colder and more stable air conditions existing during the winter season. Also concentrations on the flat were higher than those on a hillside probably reflecting the influence of thermal inversions. Wind direction influences the concentrations, they being greater when the wind flow comes across the industrial areas of the city. Some of the major sources of the elements are coal, soil, tyre wear and automobile emissions.
Adult↗
Inhibition of cytochrome P4502E1 expression by organosulfur compounds allylsulfide, allylmercaptan and allylmethylsulfide in rats.
Cytochrome P4502E1 (CYP2E1) is active in both detoxication and activation of small organic molecules. The effects of organosulfur compounds including allylsulfide (AS), allylmercaptan (AM) and allylmethylsulfide (AMS) on the expression of CYP2E1 were examined in rats. 4-Nitrophenol, aniline hydroxylase and N-nitrosodimethylamine demethylase activities, the rates of which represent the level of CYP2E1, decreased in hepatic microsomes isolated from rats treated with AS in a time-dependent manner by 45% to 90%, as compared to control. Pyrazine-induced hepatic microsomes exhibited approximately 5-fold increases in CYP2E1-catalysed metabolic activities, whereas the hepatic microsomes obtained after treatment of animals with both AS and pyrazine showed rates comparable to or less than those in control microsomes. AM or AMS suppressed constitutive and pyrazine-inducible levels of CYP2E1 similarly to AS. Immunoblot analyses of hepatic microsomes, using an anti-CYP2E1 antibody, showed that AS, AM and AMS significantly suppressed constitutive levels of CYP2E1 apoprotein after 24, 48 and 72 hr. Time-dependent induction of CYP2E1 by pyrazine was also completely blocked by treatment of animals with AS throughout the experimental period, as evidenced by immunoblot analysis. The levels of CYP2E1 apoprotein in the hepatic microsomes isolated from animals treated with both AM and pyrazine, or with both AMS and pyrazine were comparable to those in control hepatic microsomes at days 1-3 post-treatment. Treatment of rats with each of these organosulfur compounds caused no significant changes in the levels of CYP2E1 mRNA, as assessed by slot and northern blot analyses, suggesting that post-transcriptional regulation may be associated with the suppression of CYP2E1 apoprotein levels. The results of metabolic activities, immunoblot analyses and RNA blot analyses demonstrated that these organosulfur compounds are effective in suppressing constitutive and inducible expression of CYP2E1.
Allyl Compounds↗
Enhanced expression of rat microsomal epoxide hydrolase gene by organosulfur compounds.
The effects of organosulfur compounds including allylsulfide (AS), allylmercaptan (AM) and allylmethylsulfide (AMS) on the expression of microsomal epoxide hydrolase (mEH) protein and its mRNA were examined in rats. The levels of mEH induction were examined with or without concomitant treatment of animals with pyrazine, a strong inducer of mEH, in order to establish whether a common molecular basis exists for mEH induction between these structurally different xenobiotics. Immunoblot analyses using anti-rat mEH antibody showed that treatment with AS caused an approximately 4-fold increase in hepatic mEH protein levels relative to controls whereas treatment with both AS and pyrazine resulted in only minimal additive increases in the elevation of mEH. Administration of AM to rats resulted in a comparable increase in mEH levels to that caused by AS, whereas an approximately 2-fold increase was noted after AMS treatment, as compared to control. mEH levels in the hepatic microsomes isolated from animals treated with both AMS and pyrazine were, however, approximately 50% less than those from pyrazine-treated rats. Thus, AS and AM appeared to be more effective than AMS in elevating mEH, as evidenced by immunoblot analyses. The levels of mEH mRNA were increased 10-16-fold following treatment with either AS or AM, while AMS caused a 3-7-fold increase relative to control, as assessed by slot blot analysis probed with a 1.3 kb mEH cDNA. Time-dependent increases in mRNA levels by each of these organosulfur compounds were consistent with those in mEH protein levels at 3 days. A marginal additive increase in mEH mRNA levels was noted following co-administration of either AS or AM with pyrazine, whereas treatment with both AMS and pyrazine decreased mEH mRNA levels by 55%. Significant mEH mRNA increases in poly(A)+ RNA fractions were confirmed by northern blot analysis. The results demonstrate that these organosulfur compounds are inducers of mEH and that the induction involves increases in its mRNA.
Allyl Compounds↗