Abstract：
:The antidepressants, imipramine and mianserin, have been reported to cause liver damage. We investigated a role of cytochrome P450 (CYP)-mediated formation of a reactive metabolite in antidepressant-induced acute cell injury using hepatocytes isolated from male and female Wistar rats, and male Dark Agouti rats, which have different relative abundance of CYP enzymes. Culture of the hepatocytes with imipramine and mianserin caused a marked decrease in glutathione followed by protein thiol, which preceded lactate dehydrogenase leakage. The decreases in glutathione and protein thiol contents by imipramine were significantly slower in hepatocytes from male Dark Agouti rats than those from male Wistar rats, whereas no significant sex difference in Wistar rats was observed. The decrease in thiol by mianserin was significantly slower in hepatocytes from female Wistar than those from male Wistar rats, whereas no significant differences were found between Wistar and Dark Agouti males. Results consistent with alteration of the thiols were obtained for lactate dehydrogenase leakage induced by imipramine and mianserin. These findings indicated that CYP-mediated metabolic activation was involved in acute cell injury induced by the antidepressants; namely a CYP2D enzyme(s), which is deficient in Dark Agouti rats, and a male specific CYP enzyme(s) were suggested to be responsible for the cytotoxicity of imipramine and mianserin, respectively.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Masubuchi Y,Konishi M,Horie Tdoi
10.1007/s002040050599keywords:
subject
Has Abstractpub_date
1999-04-01 00:00:00pages
147-51issue
3eissn
0340-5761issn
1432-0738journal_volume
73pub_type
杂志文章abstract：:The aim of this study was to investigate the electrophilic tissue burden (ETB) formation, assessed as covalent binding of the ultimate carcinogen benzo( a)pyrene diolepoxide (BaPDE) with cellular proteins, in liver, lung and heart, as well as with haemoglobin (Hb) following repeated exposure to binary mixtures of benz...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0518-z
更新日期：2004-02-01 00:00:00
abstract：:Mouse liver CYP2A5 is induced by several structurally unrelated compounds. In intact mouse liver, pyrazole (PYR) and 4-hydroxypyrazole (4-OH) induce selectively the expression of CYP2A5 while expression of other CYPs is decreased. In this study we exposed mouse primary hepatocytes to PYR, 4-OH, 4-methylpyrazole (4Me; ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050511
更新日期：1998-05-01 00:00:00
abstract：:The covalent binding of 14C-1,1,2-trichloroethylene (14C-TRI) metabolites to calf thymus DNA in vitro and to RNA and DNA of mouse brain, lung, liver, kidney, spleen, pancreas, and testis after repeated i.p. injections has been studied. Hydrolysates of DNA reacted with 14C-TRI in vitro and hydrolysates of RNA and DNA f...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01239202
更新日期：1983-11-01 00:00:00
abstract：:Milacemide (2-n-pentylaminoacetamide) hydrochloride was administered by continuous i.v. infusion for up to 7 days, at 300 and 600 mg/kg per day to male Sprague-Dawley rats. This was intended to provide high and sustained exposure to evaluate the effect of a preterminal 24-h fast on liver lipid content. Liver lipid con...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050067
更新日期：1994-01-01 00:00:00
abstract：:Rodents are relatively insensitive to the neurotoxic effects of various organophosphorus compounds. The purpose of this investigation was to determine if differences in inactivation of CBDP could explain the strain differences in the sensitivity to neurotoxicity following administration of TOCP (tri-o-cresyl phosphate...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01973466
更新日期：1990-01-01 00:00:00
abstract：:Cadmium (Cd), an occupational and environmental pollutant, induces nephrotoxicity by primarily damaging renal proximal tubular cells. In this study, we hypothesized that pyroptosis, a caspase-1-dependent inflammatory programmed cell death mechanism, mediates Cd-induced nephrotoxicity. Human proximal tubular epithelial...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02415-8
更新日期：2019-04-01 00:00:00
abstract：:Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to i...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1673-3
更新日期：2017-01-01 00:00:00
abstract：:Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs un...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-016-1727-6
更新日期：2016-07-01 00:00:00
abstract：:Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concerns associated with BFRs argue for replacement by safe(r) alternatives. Though previous research identified the nervous system as a sensitive target organ for BFRs, the (neuro...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1187-1
更新日期：2014-04-01 00:00:00
abstract：:Forty-eight hours after a single dose of 14C-imipramine to rats, 14C-radioactivity could be measured in the following organs: liver greater than kidney greater than serum greater than fat greater than spleen greater than duodenum greater than lung greater than muscle and brain. Liver microsomes contained the main part...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00353357
更新日期：1976-12-23 00:00:00
abstract：:Teratogenic effects caused by a new nitroimidazopyridazine were examined in Wistar (WU) rats after repeated oral administration of 0, 2.5, 10, and 40 mg/kg, given on days 6-17 post coitum (p.c.) (Day of mating = Day 0) in a regular study on embryo-fetal development according to ICH S5A. At day 20 p.c., fetuses were re...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0057-5
更新日期：2006-07-01 00:00:00
abstract：:Airway smooth muscle (ASM) cell phenotypic switching played an important role in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell phenotypic switching from a mature to pro-remodeling phenotype, but the mechanism remained incompletely understood. This study was to explore the...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-012-1008-y
更新日期：2013-05-01 00:00:00
abstract：:Okadaic acid (OA) is produced by several types of dinoflagellates (marine plankton) and has been implicated as the causative agent of diarrhetic shellfish syndrome. Previous studies have shown that okadaic acid is a tumor promoter and a specific potent inhibitor of protein phosphatases and protein synthesis. These eff...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0460-0
更新日期：2003-11-01 00:00:00
abstract：:Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined....
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-018-2192-1
更新日期：2018-07-01 00:00:00
abstract：:Prudhoe Bay crude oil (PBCO) and its aliphatic, aromatic and heterocyclic fractions were tested on the developing chick embryo for (i) embryotoxicity (ii) their ability to induce hepatic and renal cytochrome P450 levels as well as hepatic, renal and pulmonary aryl hydrocarbon hydroxylase activities. On the basis of it...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00302389
更新日期：1987-08-01 00:00:00
abstract：:Reduced gluconeogenesis due to decreased activity of key gluconeogenic enzymes in liver, together with feed refusal, has been suggested to play an important role in 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-induced lethality in rats. This study was carried out to further analyse the toxicological significance of red...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050626
更新日期：1999-08-01 00:00:00
abstract：:The effect of culture medium on glutathione (GSH) dependent detoxification defence system of primary cultured hepatocyte from either male or female rats was studied. Intracellular reduced (GSH) and oxidized glutathione (GSSG), and six GSH-related enzyme activities, including GSH peroxidase (GSH Px), GSH reductase (GSH...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050345
更新日期：1996-01-01 00:00:00
abstract：:Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and de...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-015-1633-3
更新日期：2015-12-01 00:00:00
abstract：:The reversibility of quinolone-induced cartilage lesions has not been studied in detail. We treated five groups of five to seven juvenile Wistar rats (male and female; age: 5 weeks) with 2 x 600 mg ofloxacin/kg by gastric intubation on 1 day only (9:00 a.m. and 5:00 p.m.) and studied the knee joints histologically 3 d...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050301
更新日期：1996-01-01 00:00:00
abstract：:Chemical formation of dichlorvos (2, 2-dichlorovinyl dimethyl phosphate) was found to occur in mouse brain after i.p. injection of metrifonate (2, 2, 2-trichloro-1-hydroxyethyl dimethyl phosphonate). A mass fragmentographic technique was used. Different isotopic variants were used both as internal standards and to com...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00351767
更新日期：1978-10-13 00:00:00
abstract：:The comet assay is a versatile, reliable, cost-efficient, and fast technique for detecting DNA damage and repair in any tissue. It is useable in almost any cell type and applicable to both eukaryotic and prokaryotic organisms. Instead of highlighting one of the numerous specific aspects of the comet assay, the present...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-016-1767-y
更新日期：2016-10-01 00:00:00
abstract：:People living in damp buildings are typically exposed to spore and mycelial fragments of the fungi that grow on damp building materials. There is experimental evidence that this exposure to triple-helical (1, 3)-β-D glucan and low molecular weight toxins may be associated with non-atopic asthma observed in damp and mo...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1042-4
更新日期：2013-10-01 00:00:00
abstract：:Fulminant hepatitis is a serious inflammatory condition of the liver characterized by massive necrosis of liver parenchyma following excessive immune cell infiltration into the liver, and possibly causing sudden hepatic failure and medical emergency. However, the underlying mechanisms are not fully understood. Here, w...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02633-0
更新日期：2020-02-01 00:00:00
abstract：:Previous studies indicate that benzanthrone, an anthraquinone dye intermediate, caused significant depletion of ascorbic acid (AsA). In this investigation the effect of benzanthrone on the status of different forms of AsA and other bio-antioxidants such as glutathione (GSH) was studied. Oral administration of benzanth...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040100222
更新日期：2001-06-01 00:00:00
abstract：:The effect of methantheline, a quaternary ammonium compound, on the reactivation by HI 6 of soman-inhibited human erythrocyte acetylcholinesterase (AChE) was investigated in vitro using purified human erythrocyte AChE or washed human erythrocytes. Methantheline itself was found to be a mixed competitive/non-competitiv...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050243
更新日期：1995-01-01 00:00:00
abstract：:We studied the incorporation of cocaine (COC), benzoylecgonine (BE) and ecgonine methyl ester (EME) into hair from blood. At first, the time courses of three drugs in rat plasma following i.p. administration of cocaine were investigated over 360 min. AUCs of COC, BE and EME in plasma were 14.2, 60.7 and 53.4 microgram...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02035137
更新日期：1992-01-01 00:00:00
abstract：:Pulmonary fibrosis is a poorly understood pathologic condition. Carbon nanotubes (CNTs) are nanomaterials with potentials for broad applications. CNTs can induce pulmonary fibrosis in animals, a cause for concern for exposed workers and consumers. Given the large number of CNTs available on the market and the seemingl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-018-2306-9
更新日期：2018-11-01 00:00:00
abstract：:Many carcinogens and mutagens are electrophilic in nature and will react with nucleophilic sites in protein and nucleic acid. Determination of the extent of formation of these adducts of genotoxic agents with protein provides a practical method of monitoring human exposure and of determining the possible risk associat...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00296978
更新日期：1987-01-01 00:00:00
abstract：:The main purpose of this study was to verify the hypothesis that cognitive dysfunctions induced by arsenic exposure were related to the changes of D-serine metabolism in the hippocampus of offspring mice. Mother mice and their offsprings were exposed to 0, 15, 30 or 60 mg/L sodium arsenite (NaAsO2) through drinking wa...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-019-02616-1
更新日期：2020-01-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent tumor promoter ever tested in rodents. Although it is known that most of the effects of TCDD are mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact inhibition ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0601-0
更新日期：2005-01-01 00:00:00
