Abstract：
:A subchronic oral toxicity study of disobutamide, a piperidine ring compound with antiarrhythmic activity, was conducted at doses of 30, 100, and 250 mg/kg in rats, 45 mg/kg in dogs, and 90 mg/kg in monkeys. Numerous vacuoles were observed in various organs such as the liver, kidneys, heart, lungs, spleen, thymus, stomach, and choroid plexus in these animals. The epithelium of the choroid plexus (CP), however, showed severe vacuolation in rats and monkeys but not in dogs. The vacuoles corresponded to enlarged and myelin-figured lysosomes observed by electron microscopy, revealing morphological characteristics which have been reported as drug-induced phospholipidosis. In a further study, the drug penetration to cerebrospinal fluid (CSF) and the drug concentration in CP were examined in these animals. Daily po doses of 250, 45, and 90 mg/kg were, respectively, administered to rats, dogs, and monkeys to maintain approximate equivalency in peak blood concentrations across species, over a course of 35 days. The concentration of the drug in the CP was higher in rats and monkeys than in dogs, and the CSF/serum ratio of the drug concentration was extremely high in rats. The uptake of the drug by the CP in vitro was high in rats, monkeys, and dogs, in this order. In dogs, both direct contact of the drug with the CP during incubation and intraventricular administration induced vacuolation in the epithelium. From these results it was concluded that differences of the drug's penetration into the CSF and its uptake by the choroid plexus epithelium are responsible for the species differences of CP vacuolation in the animals.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Koizumi H,Watanabe M,Numata H,Sakai T,Morishita Hdoi
10.1016/0041-008x(86)90421-7subject
Has Abstractpub_date
1986-06-15 00:00:00pages
125-48issue
1eissn
0041-008Xissn
1096-0333pii
0041-008X(86)90421-7journal_volume
84pub_type
杂志文章abstract：:Nucleoside analog reverse transcriptase inhibitors (NRTIs) are known to directly inhibit mitochondrial complex I activity as well as various mitochondrial kinases. Recent observations that complex I activity and superoxide production are modulated through cAMP-dependent phosphorylation suggests a mechanism through whi...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.08.015
更新日期：2008-01-01 00:00:00
abstract：:Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration....
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1995.1065
更新日期：1995-04-01 00:00:00
abstract：:High fetal and neonatal brain levels of methyl mercury (MeHg) have been associated with the abnormal migration of neurons within the cerebellar and cerebral cortices. How MeHg interferes with cellular proliferation, migration, and differentiation is poorly understood. In this study, a cell recognition/cohesion assay b...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(86)90363-7
更新日期：1986-12-01 00:00:00
abstract：:Chemicals from anthropogenic and natural origins enter animal feed, human food and water either as undesirable contaminants or as part of the components of a diet. Over the last five decades, considerable efforts and progress to develop methodologies to protect humans and animals against potential risks associated wit...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.taap.2012.03.013
更新日期：2013-08-01 00:00:00
abstract：:Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and many of their toxic effects, including their immunotoxicities, are mediated by the activation of aryl hydrocarbon receptor (AhR). We previously reported that Aroclor 1254, one of the most widely used PCB mixtures, increased DNA fragmentatio...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2002.9389
更新日期：2002-06-01 00:00:00
abstract：:The distribution of 14C-labeled clodronate (dichloromethylene bisphosphonate), a new bisphosphonate for the treatment of osteolytic bone metastases and hypercalcemia, was studied in mice by whole-body autoradiography and by measuring the 14C activities in various tissues [14C]Clodronate was administered into the tail ...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90050-0
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2018.01.021
更新日期：2018-03-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.09.011
更新日期：2012-11-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(85)90119-x
更新日期：1985-10-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2005-06-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2009.07.016
更新日期：2009-10-15 00:00:00
abstract：:An infamous poison, arsenic also has been used as a drug for nearly 2400 years; in recently years, arsenic has been effective in the treatment of acute promyelocytic leukemia. Increasing evidence suggests that opposite effects of arsenic trioxide (ATO) on tumors depend on its concentrations. For this reason, the mecha...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2008.08.015
更新日期：2008-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90239-q
更新日期：1990-11-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(03)00158-3
更新日期：2003-07-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1997.8136
更新日期：1997-06-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2004.04.010
更新日期：2004-11-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(87)90177-3
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90184-6
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(90)90343-s
更新日期：1990-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(92)90305-c
更新日期：1992-10-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1993.1186
更新日期：1993-10-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2012.08.036
更新日期：2012-12-01 00:00:00
abstract：:Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and alt...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2014.10.007
更新日期：2014-12-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/s0041-008x(88)80006-1
更新日期：1988-08-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2011.08.012
更新日期：2011-10-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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更新日期：2018-09-15 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.2000.8989
更新日期：2000-09-01 00:00:00
abstract：:This study was undertaken to characterize the long-term toxic and carcinogenic potential of a polybrominated biphenyl (PBB) mixture in rats and mice of both sexes. Fischer 344 rats and B6C3F1 mice were given 125 po doses of PBB over a 6-month period at 0 (control), 0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg body weight/day (5...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(83)90351-4
更新日期：1983-03-30 00:00:00
