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1. |
Allyl alcohol cytotoxicity in isolated rat hepatocytes: Effects of azide, fasting, and fructose |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 1-11
LoraE. Rikans,
Yong Cai,
K. Roger Hornbrook,
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摘要:
The role of altered energy homeostasis in the lethality of allyl alcohol to isolated rat hepatocytes was studied. ATP, ADP, AMP, and viability loss (leakage of lactate dehydrogenase into the medium) were measured in isolated hepatocytes of fed or fasted rats exposed to 0.5 mM allyl alcohol. Adenine mononucleotides and cytotoxicity were determined also in hepatocytes incubated with allyl alcohol in the presence of 4 mM sodium azide or 15 mM fructose. Allyl alcohol‐induced cell death in hepatocytes of fed rats was preceded by slight decreases in ATP content and energy charge (16% and 12%, respectively). More substantial decreases in these parameters occurred in parallel with cell killing, but the effect of allyl alcohol on energy status did not exceed the effect produced by a nonlethal concentration of sodium azide. Neither azide nor fructose affected the development of allyl alcohol cytotoxicity. Moreover, allyl alcohol‐induced cytotoxicity was similar in hepatocytes of fed and fasted rats. The results suggest that altered energy homeostasis is a consequence rather than a cause of allyl alcohol‐induced hepatocyte lethality.
ISSN:0098-4108
DOI:10.1080/15287399509531939
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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2. |
Effect of oral dosing vehicles on the subchronic hepatotoxicity of carbon tetrachloride in the rat |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 13-27
K. P. Koporec,
H. J. Kim,
W. F. Mackenzie,
J. V. Bruckner,
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摘要:
Previous studies in this laboratory have shown that corn oil delayed and prolonged the gastrointestinal absorption of carbon tetrachloride (CCI4) and reduced its acute hepatotoxicity in rats. The objective of the present study was to extend the duration of ingestion of CCI4to assess vehicle effects on the subchronic oral toxicity of CCI4. Male Harlan Sprague‐Dawley rats were given doses of 0, 25, or 100 mg CCI4/kg body weight by gavage in either corn oil or a 1% Emulphor aqueous emulsion 5 times a week for 13 wk. Blood was collected at 4, 8, and 13 wk for measurement of serum enzymes. Liver samples were also taken at 13 wk for measurement of triglyceride and microsomal enzyme levels, as well as for histopathological examination. Serum enzyme levels peaked at 8 wk in the high‐dose groups, but not until 13 wk in the low‐dose animals. Effects of CCI4on serum and microsomal enzymes were of similar magnitude in the two vehicle groups. A comprehensive histopathological examination revealed no qualitative or quantitative differences between the corn oil and aqueous vehicle groups in hepatic lesions. Although CCl4and chloroform have been reported by other investigators to be more hepatotoxic to mice when given for 90 d in corn oil, current findings indicate that corn oil does not significantly alter the subchronic hepatotoxicity of CCI4in rats from that when the halocarbon is given in an aqueous medium.
ISSN:0098-4108
DOI:10.1080/15287399509531940
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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3. |
Acute‐phase reactant proteins and antioxidants in rats intoxicated chronically with paraquat |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 29-41
Kayoko Minakata,
Osamu Suzuki,
Sachiko Oh‐ishi,
Izumi Hayashi,
Shin‐ichi Saito,
Naoko Harada,
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摘要:
Paraquat dichloride at 250 ppm in the diet was fed continuously to rats. Though no apparent effect of paraquat was observed until 10 d, some rats then began to show several symptoms such as diarrhea, anorexia, epistaxis, and hypokinesia, and in some cases rats died after this period. The biochemical examination of plasma components revealed appreciable changes in the concentrations of an acute‐phase reactant protein and some vitamins that act as antioxidants. α‐Cysteine proteinase inhibitor increased by 5‐fold, and vitamin C and its radical increased by 1.5‐ and 1.7‐fold, respectively, whereas α1 proteinase inhibitor decreased slightly. Paraquat enhanced the cysteine proteinase inhibitor levels in lung, liver, and kidney by 6.2‐, 6.0‐, and 4.5‐fold of control, respectively. Among three components of α‐cysteine proteinase inhibitor, the T kininogen level of treated rat plasma was about eight‐fold higher than control, whereas the high‐molecular‐weight kininogen level was unchanged. The large increment of T kininogen was also seen in lungs of the treated rats.
ISSN:0098-4108
DOI:10.1080/15287399509531941
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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4. |
Role of retinal metabolism in methanol‐induced retinal toxicity |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 43-56
CharlesD. Garner,
EunWoo Lee,
ThomasS. Terzo,
RobertT. Louis‐Ferdinand,
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摘要:
Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate‐reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol‐induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate‐sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of fa‐wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol‐induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol‐treated rats by iv infusion of pH‐buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate‐mediated initiation of methanol‐induced retinal toxicity.
ISSN:0098-4108
DOI:10.1080/15287399509531942
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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5. |
Dual effect of nitrogen dioxide on barrier properties of guinea pig tracheobronchial epithelial monolayers cultured in an air interface |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 57-71
TimothyW. Robison,
Kwang‐Jin Kim,
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摘要:
Nitrogen dioxide (NO2) is an oxidant gas that may injure the airway epithelial lining, leading to decrements in barrier and active ion transport properties. The present studies examined alterations of bioelectric properties and solute flux by guinea pig tracheobronchial epithelial (CPTE) monolayers exposed in vitro to NO2. Confluent CPTE monolayers were exposed to NO2levels between 0.5 and 5 ppm, while controls were exposed to air. Following exposure, monolayers were mounted in Ussing chambers for measurement of transepithelial resistance (Rte) and short‐circuit current (SCC). A 1‐h exposure to 1 ppm NO2significantly increased SCC to 131.3 ± 8.7% of air controls, while Rtewith a value of 109.3 ± 13.8% was unchanged. In contrast, a 1‐h exposure to 2 or 5 ppm NO2significantly decreased Rteto 39.0 ± 1.6 or 35.5 ± 7.3% of ah controls, respectively, while SCC values of 140.3 ± 10.4 or 153.3 ± 8.6%, respectively, were also significantly elevated. A 1‐h exposure to 2 or 5 ppm NO2significantly increased sucrose permeability across CPTE monolayers to 446.8 ± 117 or 313.3 ± 39.5% of air controls, respectively, while glycerol permeability was unchanged. In contrast, a 1‐h exposure to 1 ppm NO2produced no alterations of sucrose or glycerol flux. The SCC of control CPTE monolayers (1‐h air exposure) consisted of 50% bumetanide‐sensitive and 40% amiloride‐sensitive current; exposure for 1 h to 2 ppm NO2led to no changes in the corresponding SCC components. Active ion transport (i.e., SCC) across the airway epithelium was significantly increased after exposure to NO2levels <,1 ppm with no change of paracellular pathways for diffusion, suggesting that this reactive gas alters cell membrane function. The increased SCC may lead to impairment of fluid balance and mucociliary clearance. NO2‐mediated tissue injury with levels >2 ppm primarily affects passive airway epithelial barrier functions, probably by altering tight junctions, which could result in increased transepithelial solute and fluid leakage in vivo.
ISSN:0098-4108
DOI:10.1080/15287399509531943
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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6. |
Acrylamide arrests mitosis and prevents chromosome migration in the absence of changes in spindle microtubules |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 73-86
DaleW. Sickles,
DaveA. Welter,
MarvinA. Friedman,
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摘要:
Cultured HT 1080 fibrosarcoma cells were exposed to acrylamide (ACR), an industrial neurotoxicant that disrupts neuronal intracellular transport, to determine if mitosis (another microtubule‐based intracellular transport system) was adversely affected. The number of cells arrested in mitosis increased, in a concentration‐dependent manner, from 1 to 10 mM acrylamide. A 4‐h exposure to 10 mM acrylamide increased the mitotic index by 4.5‐fold over control, comparable to the arrest caused by colchicine. In mitotic acrylamide‐exposed cells, the chromosomes remained at the metaphase plate; no changes in spindle micro‐tubules (MTs), as seen with tubulin immunofluorescence, were observed. The distance between spindle poles (interaster) was the same in control and experimental cells. The non‐neurotoxic analogue méthylène bisacrylamide had no effect in the same concentration range. The data suggest potential molecular mechanisms of action for general toxicity and neuro‐toxicity to be disruption in MT disassembly or MT‐kinetochore interactions and/or cellular homeostatis.
ISSN:0098-4108
DOI:10.1080/15287399509531944
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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7. |
In vivo and in vitro efficacy of a new carbodithioate for the mobilization of cadmium |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 87-100
Karel Bláha,
Jana Nerudová,
Helena Jehlicová,
Miroslav Cikrt,
MarkM. Jones,
PramodK. Singh,
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摘要:
Female Wistar rats with chronic cadmium intoxication (oral exposure to low dosages of CdCl2in drinking water over a period of 90 d) were used to examine the in vivo ability of a newly developed chelator, sodiumN‐(4‐methylbenzyl)‐4‐O‐(β‐D‐galactopyranosyl)‐D‐glucamme‐N‐carbodithioate (MeBLDTC), singly and in combination with sodium 4‐carboxy‐amidopiperidine‐N‐carbodithioate (INADTC) as agents to induce the biliary and urinary excretion of cadmium. The combined administration of the two dithiocarbamates, which differ greatly in molecular weight and structural features, led to a synergistic increase in the biliary excretion of cadmium and an enhanced reduction of renal cadmium levels. The use of such a coadministration produced an increase in the biliary excretion of cadmium that was more than double that expected if the compounds acted in an additive fashion. Such mixed‐chelation therapy has potential utility in the treatment of human chronic cadmium intoxication. The hepatocytes isolated from chronically Cd‐intoxicated rats were used as an in vitro screening model system for the new chelator. The plasma membrane integrity study with MeBLDTC at 0.48 mmol/20 ml of hepatocyte incubate using the trypan blue exclusion test and lactate dehydrogenase (LDH) leakage test revealed no differences in the cell viability with or without chelator. The cellular metabolic competence measured as the rate of urea synthesis also did not show any marked deviation from that of controls when incubated with MeBLDTC at three different concentrations. In the hepatocyte cultures, MeBLDTC induced a significant removal of cadmium from the hepatocytes at concentrations as low as 0.04 mmol/20 ml.
ISSN:0098-4108
DOI:10.1080/15287399509531945
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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8. |
Lack of luminal or basolateral uptake and transepithelial transport of mercury in isolated perfused proximal tubules exposed to mercury‐metallothionein |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 101-113
RudolfsK. Zalups,
M. George Cherian,
DelonW. Barfuss,
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摘要:
The lumen‐to‐bath and bath‐to‐lumen transport, cellular uptake, and toxicity of inorganic mercury bound to metallothionein (203Hg‐MT) were studied in isolated perfused S1, S2, and S3 segments of the renal proximal tubule of rabbits. Evidence of very mild toxicity was displayed in some of the segments perfused through the lumen with 18.4 μM inorganic mercury in the form of Hg‐MT. The toxic response was restricted primarily to mild swelling of the epithelial cells localized at the end of the tubular segments where the perfusion pipette was inserted into the lumen. The cells in the proximal portions of perfused S2 segments appeared to be most severely affected in that a few blebs would on occasion come off the epithelial cells. Mild cellular swelling was also observed in some S2 and S3 segments that were exposed to 18.4 μM inorganic mercury in the form of Hg‐MT in the bath. The swelling was more generalized, involving all the epithelial cells along the perfused segment. Very little, or no, measurable lumen‐to‐bath or bath‐to‐lumen transport of Hg as Hg‐MT could be detected in any of the 3 perfused segments of the proximal tubule during 40–45 min of perfusion. The complex of Hg‐MT appeared to behave in a manner similar to that of the volume marker [3H]‐L‐glucose. The lack of tubular transport of Hg as Hg‐MT was confirmed by little or no measurable uptake and accumulation of inorganic mercury in the tubular epithelial cells. Thus, our findings indicate that the Hg‐MT complex is not taken up avidly in isolated perfused S1, S2, or S3 segments of the proximal tubule.
ISSN:0098-4108
DOI:10.1080/15287399509531946
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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9. |
Incubation temperature as a modifying factor on survival ofTenebrio molitorreared in selenium‐containing media |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 115-122
A. Audas,
G. R. Hogan,
H. Razniak,
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摘要:
Newly emerged Tenebrio molitor were reared at 4, 25, and 37°C in nutrient media supplemented with sodium selenate (0.0125, 0.0200, 0.0500, and 0.1000%). Ten insects comprised each group. Controls were maintained in unsupplemented medium at the same temperatures as the experimental groups. Survival percentages were determined. Survival curves were estimated at given times postincubation. Controls at 4 and 37°C showed an increased lethality compared to those insects at 25°C. Data indicate that 4°C had a protective effect on survival for insects reared in media containing the three highest concentrations of selenium. For insects at 37°C, killing was striking and equivalent for all groups, irrespective of media supplementation.
ISSN:0098-4108
DOI:10.1080/15287399509531947
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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10. |
I letter to the editor |
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Journal of Toxicology and Environmental Health,
Volume 44,
Issue 1,
1995,
Page 123-134
JeraldA. Fagliano,
JonathanE. Savrin,
LeahZ. Ziskin,
WilliamE. Parkin,
JamesA. Brownlee,
Michael Gochfeld,
Paul Lioy,
RichardA. Anderson,
Theodore Colton,
John Doull,
JamesG. Marks,
RalphG. Smith,
GretchenM. Bruce,
BrentL. Finley,
DennisJ. Paustenbach,
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ISSN:0098-4108
DOI:10.1080/15287399509531948
出版商:Taylor & Francis Group
年代:1995
数据来源: Taylor
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