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1. |
ROLE OF PROLIFERATION IN THE TOXICITY OF FUMONISIN B1: ENHANCED HEPATOTOXIC RESPONSE IN THE PARTIALLY HEPATECTOMIZED RAT |
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Journal of Toxicology and Environmental Health, Part A,
Volume 60,
Issue 7,
2000,
Page 441-457
Wu Li, Ronald T. Riley, Kenneth A. Voss, William P. Norred,
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摘要:
Fumonisin mycotoxins are common contaminants of maize and cause several fatal animal diseases. Liver is a target organ of fumonisins in intact animals, but liver slices and primary hepatocytes, which do not proliferate in culture, are resistant to fumonisin exposure. Hepatoma cell lines, on the other hand, undergo cell division in culture and are sensitive to the toxic effects of fumonisins. It was therefore hypothesized that fumonisin cytotoxicity is dependent on cell proliferation. To test this hypothesis, the partially hepatectomized rat was used as a model to determine whether fumonisin produced greater toxicity in rapidly proliferating liver in vivo. Rats were dosed intraperitoneally with fumonisin B1(FB1) 24 h after sham operation or partial hepatectomy (PH) and were killed 24 h later. The dose-related increase in free sphingoid bases (a biomarker of fumonisin exposure) was enhanced in the PH-treated rats. Serum cholesterol and enzymes were higher in PH-treated rats dosed with FB1than in those given PH without FB1or in sham-operated, FB1-dosed rats. Multiple daily doses of FB1after surgery elevated the number of apoptotic hepatocytes in both sham-operated and PH-treated rats to about the same degree, suggesting that apoptosis is not associated with the enhanced cytotoxicity of FB1in regenerating liver. Proliferating cells appear to be more sensitive to the toxic effects of fumonisins. This enhanced cytotoxicity may be related to the increased ability of fumonisins to disrupt sphingolipid metabolism in hepatectomized rats, but this is yet to be determined.
ISSN:1528-7394
DOI:10.1080/00984100050079511
出版商:Informa UK Ltd
年代:2000
数据来源: Taylor
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2. |
FACTORS INVOLVED IN HEPATIC GLUTATHIONE DEPLETION INDUCED BY ACUTE ETHANOL ADMINISTRATION |
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Journal of Toxicology and Environmental Health, Part A,
Volume 60,
Issue 7,
2000,
Page 459-469
Dal W. Choi, Sung Y. Kim, Sang K. Kim, Young C. Kim,
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摘要:
Factors implicated in changes of the hepatic glutathione concentration following acute ethanol administration were examined in rats. Adult female rats were treated with either ethanol (4 g/kg, po) or an isocaloric glucose solution. The hepatic reduced glutathione (GSH) concentration decreased rapidly after ethanol intake with a maximum diminution, approximately 50% of the control value, being observed att= 6 h. The hepatic GSH concentration gradually increased, and finally rebounded at 24 h after ethanol ingestion. The dose of ethanol induced a transient increase in the oxidized glutathione (GSSG) and GSSG/GSH ratio, which was associated with a significant reduction in GSH rather than elevation in GSSG. The activity of g-glutamylcysteine synthetase (GCS), the rate-limiting enzyme for glutathione synthesis, and the cysteine concentration in liver were also measured. The GCS activity was depressed to approximately 80% of the control value att= 2.5 h followed by rapid recovery, but no difference in the hepatic cysteine concentration between control and ethanol treated rats was observed for 24 h, suggesting that the reduction in glutathione synthesis may not play a major role in the significant depletion of this tripeptide in liver. The total glutathione concentration was measured both in prehepatic and posthepatic inferior vena cava blood. The glutathione concentration in posthepatic blood was approximately twice as high as that of prehepatic blood in control rats. Acute ethanol administration doubled the elevation of glutathione in posthepatic blood measured att= 2.5 h. The sinusoidal efflux of glutathione estimated from the increase in blood glutathione concentration was greater than the total amount of its depletion in the liver of rats treated with ethanol. The results suggest that in the liver of rats treated acutely with ethanol, glutathione efflux plays the most important role in the reduction of this tripeptide, which would be aggravated by a transient decrease in glutathione synthesis and by increased consumption in association with its metabolism.
ISSN:1528-7394
DOI:10.1080/00984100050079520
出版商:Informa UK Ltd
年代:2000
数据来源: Taylor
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3. |
CHLORINATION OF DRINKING WATER AND SEX RATIO AT BIRTH IN TAIWAN |
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Journal of Toxicology and Environmental Health, Part A,
Volume 60,
Issue 7,
2000,
Page 471-476
Chun-Yuh Yang, Bi-Hua Cheng, Shang-Shyue Tsai, Trong-Neng Wu, Te-Yao Hsu, Kuo-Cherng Lin,
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摘要:
Chlorination has been the major strategy for disinfecting drinking water in Taiwan. The objective of the present study was to determine whether the chlorination of drinking water was associated with abnormal sex ratios, an indicator of exposure to pollutants. A "chlorinating municipality" (CHM) was defined as one in which more than 90% of the municipality population was served with chlorinated water. A "nonchlorinating municipality" (NCHM) was one in which less than 5% of the municipality population was served with chlorinated water. The results of this study found no association between the use of chlorinated drinking water and abnormal sex ratios at birth in Taiwan. The imbibing of chlorinated water may not reflect contaminant exposure using sex ratio as a biomonitor.
ISSN:1528-7394
DOI:10.1080/00984100050079539
出版商:Informa UK Ltd
年代:2000
数据来源: Taylor
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4. |
LUNG TOXICITY OF PARAQUAT IN THE RAT |
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Journal of Toxicology and Environmental Health, Part A,
Volume 60,
Issue 7,
2000,
Page 477-487
Chung-Ming Chen, Ahai C. Lua,
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摘要:
In a rat model of paraquat-induced lung injury, pulmonary alveolar lavage fluid metabolic parameters were assessed to establish damage, and the use of surfactant was employed as a protective agent. Three groups of adult male Sprague-Dawley rats received intraperitoneal injection of paraquat (35 mg/kg body weight) in 1 ml saline, or received 1 ml saline, or no material. On d 3, 7, 14, and 21 after injection, pressure-volume curves and pulmonary alveolar lavage fluids were obtained. On d 3 paraquat significantly increased the lung wet/dry weight ratio and protein content but lowered phosphatidylcholine levels. There were no marked changes at other time points in the parameters examined. The pressure-volume curves initially moved downward and to the right on d 3 and 7 and then returned to control levels in the paraquat-treated rats. Immediate intratracheal administration of Survanta after paraquat injection (70 mg/kg body weight) tended to increase the survival rate on d 1 compared to rats without Survanta administration. Our results suggest that administration of exogenous surfactant may play a role in the treatment of patients poisoned with paraquat.
ISSN:1528-7394
DOI:10.1080/00984100050079548
出版商:Informa UK Ltd
年代:2000
数据来源: Taylor
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5. |
TOXICITY EVALUATION OF PETROLEUM BLENDING STREAMS: INHALATION SUBCHRONIC TOXICITY/NEUROTOXICITY STUDY OF A LIGHT CATALYTIC REFORMED NAPHTHA DISTILLATE IN RATS |
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Journal of Toxicology and Environmental Health, Part A,
Volume 60,
Issue 7,
2000,
Page 489-512
C. Schreiner, Q. Bui, R. Breglia, D. Burnett, F. Koschier, E. Lapadula,
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摘要:
A 13-wk whole-body inhalation study was conducted with Sprague-Dawley CD rats (16/sex/group) exposed to a light catalytic reformed naphtha distillate (LCRN-D, CAS number 64741-63-5) at target concentrations of 0, 750, 2500, and 7500 ppm for 6 h/d, 5 d/wk. Sixteen rats per sex in the control and high-dose groups were maintained after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, throughout exposure and after the recovery period. Neuropathology was evaluated at termination. No test-related mortality or effects on physical signs, body weight, food consumption, or clinical chemistry were observed. In males exposed to 7500-ppm LCRN-D, a statistically significant decrease in white blood cell counts and lymphocyte counts was observed at the termination of exposure that was not present in animals after the 4-wk recovery period. However, mean corpuscular volume was slightly decreased in high-dose males after the recovery period. Statistically significant increases in kidney weights relative to body weights in 7500-ppm male rats correlated with microscopically observed hyaline droplet formation and renal tubule dilation, indicative of light hydrocarbon nephropathy, a condition in male rats that is not toxicologically significant for humans. Statistically significant decrease in absolute and relative spleen weights in 7500-ppm male rats correlated with decreases in hematologic parameters but had no microscopic correlate and was not observed in animals after 4 wk of recovery. This mild, reversible effect in white blood cell populations may relate to the presence of aromatics in the distillate. The only effect of LCRN-D on neurobehavioral parameters was significantly higher motor activity counts among high-dose (7500 ppm) males after the 4-wk recovery period, suggesting a possible delayed effect of LCRN-D. However, there was no evidence of hyperactivity or abnormal behavior from the functional observational battery evaluations, and there were no microscopic changes in neural tissue to support this observation. The no-observed-adverse-effects level (NOAEL) for LCRN-D was 2500 ppm for both subchronic toxicity and neurotoxicity. The no-observed-effects level (NOEL) was 750 ppm.
ISSN:1528-7394
DOI:10.1080/00984100050079557
出版商:Informa UK Ltd
年代:2000
数据来源: Taylor
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