Abstract:
:Previous studies indicated that the enantiomers of thalidomide and its analogue EM12 exhibit differing teratogenic potencies. Unfortunately, these substances proved to be unstable and racemised considerably, so that the intrinsic teratogenic potencies of the pure enantiomers were difficult to elucidate. We have therefore studied the teratogenicity of the enantiomers of 2-n-propyl-4-pentenoic acid (4-en-VPA), a metabolite of the human and animal teratogen valproic acid (VPA). Both enantiomers were prepared via asymmetric synthesis using (R)- and (S)-1-amino-2-(methoxymethyl)pyrrolidine (RAMP: SAMP). The determination of the absolute configuration and of the optical purities is described. They were administered as single intraperitoneal injections during early organogenesis in the mouse (day 8 of gestation), a period shown to be highly susceptible to interference with neural tube closure by VPA. S-(-)-4-en-VPA was significantly more teratogenic (formation of exencephaly) and embryotoxic (incidence of embryolethality and fetal growth retardation) than R-(+)-4-en-VPA. The rate of neural tube defects (exencephaly) produced by the S-enantiomer was about 4 times higher than that produced by the R-enantiomer. The S-enantiomer of 4-en-VPA is the first analogue of VPA with higher teratogenic potency than the parent drug. Our results show that racemic mixtures may consist of enantiomers with greatly differing teratogenic potencies. These findings may lead to the development of clinically useful drug enantiomers with low teratogenic potencies, and assist in studies of molecular mechanisms in drug and chemical teratogenesis.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Hauck RS,Nau Hdoi
10.1016/0378-4274(89)90099-4subject
Has Abstractpub_date
1989-10-01 00:00:00pages
41-8issue
1eissn
0378-4274issn
1879-3169pii
0378-4274(89)90099-4journal_volume
49pub_type
杂志文章abstract::We investigated the cytotoxic effects of formaldehyde (FA) on lymphocytes. FA-exposed mice showed a profound reduction not only in the number of natural killer (NK) cells but also in the expression of NK cell-specific receptors, but these mice did not exhibit decreases in the numbers of T or B lymphocytes. FA exposure...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2013.09.008
更新日期:2013-11-25 00:00:00
abstract::There are multiple lines of evidence showing that environmental toxicants including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a phenylpyrazole insecticide that acts on insect GABA receptors. Although the action of FPN is restricted to insect neuronal or muscular transmitter systems, a few stu...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2012.02.022
更新日期:2012-05-20 00:00:00
abstract::The effect of chlordimeform (CDM) treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment. After acute administration of chlordimeform (100 mg/kg, i.p., 1 hour before killing) differential effects were observed in various parameter...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90072-3
更新日期:1983-08-01 00:00:00
abstract::In this paper, the difficulties of genetic screening of occupationally exposed subjects for the evaluation of retrospective, and prospective, health risk assessments is illustrated with reference to glutathione S-transferase (GST) function. Individual differences in the magnitude and half-life of adduct levels, derive...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(02)00191-1
更新日期:2002-08-05 00:00:00
abstract::In the field of aquatic toxicology, quantitative structure-activity relationships (QSARs) have developed as scientifically credible tools for predicting the toxicity of chemicals when little or no empirical data are available. A fundamental understanding of toxicological principles has been considered an important com...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(95)03374-t
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND:Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induce...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.05.023
更新日期:2017-08-05 00:00:00
abstract::Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the biosphere. ERalpha regulates the expression of genes involved in growth and development, and plays an important role in breast cancer. The present study focuses attention on the effect of HCB (0.005, 0.05, 0.5, 5 microM) on cell prolifera...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2009.10.026
更新日期:2010-02-01 00:00:00
abstract::The toxic mechanism of endosulfan, a widely used organochlorine pesticide, was investigated in Saccharomyces cerevisiae and human cell lines. A concentration-dependent inhibition of cell growth was observed when S. cerevisiae was exposed to endosulfan, and its cytotoxicity (IC(50)) was found to be 49 microM and 86 mic...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.03.004
更新日期:2004-07-15 00:00:00
abstract::The people studied were male volunteers without occupational and dietary exposure to PAH: 27 smokers (10 cigarettes or more) and 27 non-smokers matched for age and socio-professional category. For each person, all the 24h voided urine samples were reassembled in a single sample. 1-Hydroxypyrene (1-OHPy) and 3-hydroxyb...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2005.09.019
更新日期:2006-04-10 00:00:00
abstract::Benzene is an occupational and environmental toxicant. The major health concern for humans is acute myelogenous leukemia. To exert its toxic effects, benzene must be metabolized by cytochrome P450 to phenol and subsequently to catechol and hydroquinone. Previous research has implicated CYP2E1 in the metabolism of phen...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(01)00441-6
更新日期:2001-12-15 00:00:00
abstract::Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immun...
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
abstract::Administration of carcinogenic doses of urethane to male rats (for 30 days) and to females (for 45 days) caused degranulation of microsomes of livers and lungs to approx. 15 and 35%, respectively. The cholesterol levels also declined more than 50% in urethane-treated rats when compared with controls. Studies on struct...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(83)90170-4
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVES:Determine uptake of furan, a potential human carcinogen, in waterpipe tobacco (WPT) smokers in home settings. METHODS:We analysed data from a US convenience sample of 50 exclusive WPT smokers, mean age 25.3 years, and 25 non-smokers, mean age 25.5 years. For WPT smokers, data were collected at a home visit ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2020.08.002
更新日期:2020-10-15 00:00:00
abstract::Treatment of pregnant C57BL/6N mice with 2,3,7,8-tetrachlorodibenzofuran (TCDF) (0, 250, 500, and 1000 micrograms/kg on gestation day 10 or 0, 10, 30, 50, and 100 micrograms/kg on gestation days 10-13) results in dose-related increases in isolated cleft palates and hydronephrotic kidneys in the offspring. TCDF is tera...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90145-0
更新日期:1984-02-01 00:00:00
abstract::Heart rate (HR) and body core temperature (Tco) were monitored in unanesthetized, unrestrained adult Sprague-Dawley rats following intraperitoneal administration of 0, 10, 30, or 60 mg/kg of the pesticide chlordimeform (CDM). Significant non-dose-related decreases were observed in both HR and Tco in all treated groups...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90208-6
更新日期:1987-02-01 00:00:00
abstract::To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard IS...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2016.09.012
更新日期:2016-11-16 00:00:00
abstract::The necessity to protect humans from the adverse effects of chemicals on structure and function of the developing and/or mature nervous system is increasingly recognized among regulatory bodies throughout the world. Whereas structural changes dominated much of neurotoxicological research in the past, functional marker...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/0378-4274(92)90195-p
更新日期:1992-12-01 00:00:00
abstract::Ethanolamine, a positively charged hydrophilic component of the phosphatidylethanolamine (PE) which is also a precursor of phosphatidylcholine (PC), enhances the repair processes 24 h after carbon tetrachloride (CCl4) intoxication of mouse liver. Ethanolamine quickly reduced aminotransferase activity released in the s...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(97)00112-4
更新日期:1998-01-31 00:00:00
abstract::Most studies on the adverse effects of air pollution have focused on respiratory and cardiovascular diseases, and there are relatively few studies on eye diseases following exposure of ambient particulate matter (PM). Epidemiological and clinical researches correlating the eye and PMs have recently received attention....
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2017.12.012
更新日期:2018-03-01 00:00:00
abstract::Male mice (Q strain) received a single i.p. injection of 14 organophosphorus compounds, including 11 insecticides, administered on separate occasions. After a recovery period of 10 to 15 days, the cytogenic effects were analyzed in primary spermatocytes at diakinesis-metaphase I corresponding to the treatment of A4-B ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90090-0
更新日期:1984-06-01 00:00:00
abstract::The effect of a single intravenous (i.v.) injection of cadmium nitrate was investigated in livers of male Wistar rats. A significant increase in liver weight, accompanied by an elevation of total hepatic DNA content was observed. DNA synthesis as measured by the incorporation of [3H]thymidine, was found to be 6 times ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(84)90020-1
更新日期:1984-12-01 00:00:00
abstract::Single doses of primaquine did not produce methemoglobinemia in beagle bitches. Repeated daily administration for 12 days produced a gradually rising level of methemoglobin over that time period, unaccompanied by depletion of erythrocytic reduced glutathione. Primaquine was mutagenic in the Ames test in Salmonella typ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(87)90197-4
更新日期:1987-05-01 00:00:00
abstract::Diethanolamine (DEA), a secondary amine found in a number of consumer products, reportedly induces liver tumors in mice. In an attempt to define the tumorigenic mechanism of DEA, N-nitrosodiethanolamine (NDELA) formation in vivo and development of choline deficiency were examined in mice. DEA was administered with or ...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(99)00197-6
更新日期:2000-04-03 00:00:00
abstract::The effects of menadione on activities and expression of cytochrome P450 (CYP) 1A subfamily (CYP1A) isozymes in rat hepatic tissue were examined. When rats were treated orally with 15 mg/kg menadione for 4 days, the elevation of hepatic CYP1A1/1A2 specific activities in microsomal preparations was detected with approx...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2004.10.001
更新日期:2005-02-15 00:00:00
abstract::Pregnant mice of C57BL/6 and DBA/2 inbred strains were exposed to cigarette smoke during days 1-18 of pregnancy. Both mothers and offspring were killed at the age of 21-22 weeks, and ovaries were studied with respect to the number of primordial follicles and small primary follicles. In additional studies, 7,12-dimethy...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/0378-4274(85)90103-1
更新日期:1985-04-01 00:00:00
abstract::Occupational exposure to thallium (Tl+) is known to be responsible for severe neurological manifestations in humans, including ataxia and paralysis; however, little is known yet about the precise mechanism of toxicity elicited by this heavy metal at sublethal doses and its brain distribution after chronic or subchroni...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00200-9
更新日期:2000-07-27 00:00:00
abstract::The purpose of the study was to investigate the neurotoxic effect of multi-walled carbon nanotubes (MWCNTs) on the properties of glutamatergic synaptic transmission in rat's hippocampal slices using whole-cell patch clamp technique. The amplitude and frequency of excitatory postsynaptic current (EPSC) were accessed on...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2014.06.036
更新日期:2014-09-17 00:00:00
abstract::The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick's laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, u...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.03.005
更新日期:2008-05-30 00:00:00
abstract::Epidemiological studies have demonstrated a clear association between betel nut chewing and an increased risk for oral mucosal lesions. Arecoline, the most abundant betel alkaloid, is considered the most important etiologic factor in betel nuts. In addition, most betel nut chewers are also smokers. In order to elucida...
journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/s0378-4274(00)00262-9
更新日期:2000-12-20 00:00:00
abstract::Nerve agent toxicity is primarily due to the synaptic build up of toxic levels of acetylcholine. The acute lethal effects of the nerve agents are generally attributed to respiratory failure caused by a combination of effects at both central and peripheral levels and are further complicated by copious secretions, muscl...
journal_title:Toxicology letters
pub_type: 杂志文章,评审
doi:10.1016/j.toxlet.2011.09.022
更新日期:2012-01-05 00:00:00