Abstract：
:The peripheral-type benzodiazepine receptor (PBR), a putative receptor in Leydig cells, modulates steroidogenesis. Since benzodiazepines are commonly used in regional anesthesia, their peripheral effects need to be defined. Therefore, this study set out to investigate in vitro effects of the benzodiazepine midazolam (MDZ) on Leydig cell steroidogenesis, and the possible underlying mechanisms. The effects of MDZ on steroidogenesis in primary mouse Leydig cells and MA-10 Leydig tumor cells were determined by radioimmunoassay. PBR, P450scc, 3beta-HSD and StAR protein expression induced by MDZ was determined by Western blotting. Inhibitors of the signal transduction pathway and a MDZ antagonist were used to investigate the intracellular cascades activated by MDZ. In both cell types, MDZ-stimulated steroidogenesis in dose- and time-dependent manners, and induced the expression of PBR and StAR proteins, but had no effect on P450scc and 3beta-HSD expressions. Moreover, H89 (PKA inhibitor) and GF109203X (PKC inhibitor) attenuated MDZ-stimulated steroid production. Interestingly, the MDZ antagonist (flumazenil) did not decrease MDZ-induced steroid production in both cell types. These results highly indicated that MDZ-induced steroidogenesis in mouse Leydig cells via PKA and PKC pathways, along with the expression of PBR and StAR proteins. In addition, MDZ at high dosages induced rounding-up, membrane blebbing, and then death in MA-10 cells. In conclusion, midazolam could induce Leydig tumor cell steroidogenesis, and high dose of midazolam could induce apoptosis in Leydig tumor cells.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
So EC,Chang YT,Hsing CH,Poon PW,Leu SF,Huang BMdoi
10.1016/j.toxlet.2009.10.017subject
Has Abstractpub_date
2010-02-01 00:00:00pages
169-78issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(09)01472-6journal_volume
192pub_type
杂志文章abstract：:Asthma is a common chronic inflammatory disease which severely reduces the quality of life in patients. Studies have demonstrated that both PM2.5 and cold stress contribute to the development of asthma. However, the combined effects of these two risking factors are unknown. In this study, we investigated the combined ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.09.011
更新日期：2019-11-01 00:00:00
abstract：:Cisplatin, a widely used chemotherapeutic drug, causes ototoxicity in a large percentage of patients. The purpose of this study was to determine the efficacy of epicatechin (EC) as an otoprotective agent to prevent cisplatin toxicity and to investigate the molecular mechanism of EC. The effects of EC on cisplatin-indu...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.09.013
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(95)80008-2
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abstract：:A single intravenous injection of 4-hydroxyaminoquinoline 1-oxide in a dose of 9 mg/kg induced exocrine adenomas of the pancreas in a significantly higher rate in male than in female rats. Castration following HAQO administration diminished the incidence of the pancreatic tumors in male rats. A combined treatment with...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90009-6
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pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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更新日期：1989-12-01 00:00:00
abstract：:Primary cultures of rat hepatocytes were exposed to various concentrations of L-asparaginase derived from Escherichia Coli. Protein synthesis was inhibited by about 33% and cellular glutamine was reduced proportionally to the enzyme concentration. However, protein synthesis was inhibited only by amounts of enzyme able...
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pub_type： 杂志文章
doi：10.1016/0378-4274(86)90113-x
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.03.015
更新日期：2018-06-01 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
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更新日期：2003-04-11 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(00)00220-4
更新日期：2000-08-16 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2003.09.003
更新日期：2003-12-15 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.02.001
更新日期：2013-04-26 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2015.07.012
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2014.06.020
更新日期：2014-09-02 00:00:00
abstract：:Short- and medium-term rodent bioassays have been proposed under ICH guidelines for use in testing for the carcinogenic potential of pharmaceuticals. Further evaluation of these models is needed urgently and coordinated efforts are in progress worldwide to expand the available database. Models currently being investig...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00227-1
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abstract：:Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rat...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.11.016
更新日期：2018-02-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are ubiquitous environmental pollutants found in tobacco smoke, air pollution, and grilled foods. Reactive metabolites and reactive oxygen species generated during PAH metabolism are detoxified by reactions involving glutathione (GSH). Early life...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.11.017
更新日期：2014-10-15 00:00:00
abstract：:In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We car...
journal_title：Toxicology letters
pub_type： 历史文章,杂志文章
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更新日期：2018-09-01 00:00:00
abstract：:Central nervous system dysfunctions (most notably microencephaly and mental retardation) are among the most significant effects of in utero exposure to ethanol. Ethanol causes alterations of both neuronal and glial cells. In particular, ethanol has been shown to inhibit proliferation of astroglial cells stimulated by ...
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pub_type： 杂志文章,评审
doi：10.1016/j.toxlet.2003.12.020
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.06.012
更新日期：2012-09-03 00:00:00
abstract：:In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 microg of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurem...
journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00188-5
更新日期：2000-01-05 00:00:00
abstract：:Benzodiazepines have wide-spread used in pharmacotherapy for their anxiolytic, myorelaxant, hypnotic, amnesic and anticonvulsive properties. Despite benzodiazepines are used in clinics over 50 years, they have not been surprisingly tested for capability to induce major drug-metabolizing cytochromes P450. In the curren...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.01.004
更新日期：2010-03-15 00:00:00
abstract：:Troglitazone (Tro) is a thiazolidinedione antidiabetic drug that was withdrawn from the market due to its association with idiosyncratic severe liver injury. Tro has never induced liver injury in experimental animals in vivo. It was assumed that the species differences between human and experimental animals in the pha...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.08.001
更新日期：2012-10-02 00:00:00
