Abstract：
:Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study the kinetics of absorption of topically applied drugs. Their skin has structural properties very similar to human skin. However, regional distribution differences in esterase activity from site-to-site could influence cross-species extrapolation. Investigation of the regional site variation of minipig skin esterase activity will facilitate standardization of topically applied drug studies. Furthermore, the characterization of regional skin variation, will aid in translation of minipig results to better predictions of human esterase activity. Here we report the variation in rates of hydrolysis by minipig skin taken from different regional sites, using the esterase-selective substrates: phenyl valerate (carboxylesterase), phenyl acetate (arylesterase) and p-nitrophenyl acetate (general esterase). Skin from ears and back of male minipig showed higher activity than female. Skin from minipig ears and the back showed the highest level of esterase activity and was similar to human breast skin used in vitro absorption studies. These results suggest that skin from the minipig back is an appropriate model for preclinical human skin studies, particularly breast skin. This study supports the use of the minipig, with topical application to the back, as a model for the investigation of pharmacokinetics and metabolism of ester prodrugs.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Jewell C,Prusakiewicz JJ,Ackermann C,Payne NA,Fate G,Williams FMdoi
10.1016/j.toxlet.2007.07.004subject
Has Abstractpub_date
2007-09-10 00:00:00pages
118-23issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(07)00786-2journal_volume
173pub_type
杂志文章abstract：:The mammalian xenobiotic-metabolizing sulfotransferases are cytosolic enzymes, which form a gene superfamily (SULT). Ten distinct human SULT forms are known. Two SULT forms represent splice variants, the other forms are encoded by separate genes. Common functional polymorphisms of the transcribed region are known for ...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(99)00214-3
更新日期：2000-03-15 00:00:00
abstract：:This study involved an attempt to establish a new photosafety screening system for dermally-applied chemicals consisting of a reactive oxygen species (ROS) assay and an in vitro skin permeation test. The ROS assay was undertaken to evaluate photoreactivity of six test compounds, acridine (ACD), furosemide (FSM), hexac...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.09.016
更新日期：2019-12-15 00:00:00
abstract：:Exercising volunteers exposed in chambers to as little as 80 ppb O3 for several hours exhibit impaired lung function and irritative lower airway symptoms. Comparable changes occur among children and young adults exposed to summer smog containing O3. Intensity of the response is reproducible but varies widely among ind...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(95)03565-6
更新日期：1995-12-01 00:00:00
abstract：:A study has been made of the effect of cadmium chloride and zinc acetate on the adherence of Streptococcus faecalis, Escherichia coli and Candida albicans to buccal cells from man. Cadmium led to a significant decrease in the adherence of the three microorganisms tested. Zinc increased the adherence of S. faecalis and...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90207-2
更新日期：1983-02-01 00:00:00
abstract：:Pyrethroids are neurotoxic insecticides showing significant selective toxicity on insects over mammals, but effects on mammalian nervous system are not negligible. These substances act on the voltage-gated sodium channel, prolonging the duration of the open state. The present study focused on the effect of the pyrethr...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2016.12.012
更新日期：2017-02-05 00:00:00
abstract：:The main objective of this work was to assess the potentiality of in vitro models to study and understand the uranium-induced cytotoxicity on renal cells. Cytotoxicity and morphological studies were performed in a tubular proximal original established cell line (LLC-PK1 cell line). Dose-dependent cytotoxicity response...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00371-3
更新日期：1999-02-22 00:00:00
abstract：:Xenobiotic exposure is a risk factor in the etiology of neurodegenerative disease. It was recently hypothesized that restricted exposure during brain development could predispose for a neurodegenerative disease later in life. As neuroinflammation contributes to progressive neurodegeneration, it is suspected that neuro...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.02.001
更新日期：2014-10-15 00:00:00
abstract：:Methylglyoxal (MG) is a metabolite of glucose. The serum MG level is increased in diabetic patients, and MG is implicated in diabetic complications related to embryonic development injury. We previously reported cytotoxic effects of MG on mouse embryonic stem cells and blastocysts, and a further association with defec...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.01.007
更新日期：2010-04-01 00:00:00
abstract：:Effects of vitamin E on cell morphology and cellular protein thiols under oxidative stress was investigated in cultured rat hepatocytes with different vitamin E status. Hepatocytes were incubated in the presence or absence of 100 microM alpha-tocopherol succinate for 24 h then treated with 1.5 mM t-butyl hydroperoxide...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(96)03793-9
更新日期：1996-12-16 00:00:00
abstract：:Triphenyltin (TPT) is an organotin compound and may be an endocrine disruptor, impairing the male reproductive system. However, the effect of short-term TPT exposure on stem Leydig cell regeneration later on remains unknown. Here, we show that TPT affects stem Leydig cell regeneration in the adult rat testis. Adult ma...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2019.02.010
更新日期：2019-05-15 00:00:00
abstract：:A previous study revealed that a single i.p. administration of 6 mg/kg body wt. of mercuric chloride (MC) durably inhibits the rat cerebral microvascular Na+/K(+)-ATPase activity [1]. In this study, cerebral microvessels isolated 18 h after MC treatment were compared to those obtained from control rats and subsequentl...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(94)90127-9
更新日期：1994-02-15 00:00:00
abstract：:The modern environmental awareness leads to the realisation that the human metabolism is stressed by a huge number of chemical substances. Generally, these background exposures, consisting predominantly from natural and partly from industrial as well as life style sources, are tolerated without any adverse effects. Pe...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(99)00040-5
更新日期：1999-06-30 00:00:00
abstract：:Dimethocaine (DMC), a synthetic derivative of cocaine, is distributed and consumed as "new psychoactive substance" (NPS) without any safety testing at the forefront. It is mainly metabolized by N-acetylation, N-deethylation or hydroxylation. Therefore, the aim of the presented study was to determine the human NAT and ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.11.033
更新日期：2014-02-10 00:00:00
abstract：:Although building constructions are a recurring part of urbanization, the health risk of particulate matters (PM) originating from such activities have seldom been subjected to detailed studies. We sought to characterize the relative risk of air borne PM collected from different heights (ground and top floor) of a bui...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.08.002
更新日期：2015-11-04 00:00:00
abstract：:1,2-Dioxetanes, very reactive and high energy molecules, are involved as labile intermediates in dioxygenase-activated aerobic metabolism and in physiological processes. Various toxicological tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonuclease-sensitive s...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(93)90045-y
更新日期：1993-04-01 00:00:00
abstract：:The interaction of zinc(II) on the toxicokinetics of 2,5-hexanedione (2,5-HD), the ultimate toxic metabolite of n-hexane, was performed by quantifying the changes of two urinary biomarkers, free 2,5-HD and pyrrole derivatives, in rats exposed to 2,5-HD and to 2,5-HD plus zinc acetate. Eight groups of Wistar rats were ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(00)00298-8
更新日期：2001-02-03 00:00:00
abstract：:The metabolic activity of pre-implantation blastocysts recovered from delayed mice before and after administration of lead was estimated by measuring their oxygen consumption using a spectrophotometer technique. Normal blastocysts, activated for implantation, increased their oxygen consumption by about 50% compared wi...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(91)90163-z
更新日期：1991-05-01 00:00:00
abstract：:Eugenol, a natural phenolic constituent of clove oil, has a wide range of applications in medicine as a local antiseptic and anesthetic. However, the effect of eugenol on human glioblastoma is unclear. This study examined whether eugenol elevated intracellular free Ca(2+) levels ([Ca(2+)]i) and induced apoptosis in DB...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2014.10.023
更新日期：2015-01-05 00:00:00
abstract：:Blood lead concentrations (Pb-B, microgram/100 ml) was measured in children and adults, both sexes, living in and around Liège (control group, n = 859) and in the urban center of Verviers (exposed group, n = 568) where houses with lead piping are supplied with corrosive drinking water. In control children, the mean Pb...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90077-1
更新日期：1981-01-01 00:00:00
abstract：:Intraperitoneal injection (50 mg/kg) of 2-nitropropane (2-NP) induced lipid accumulation, centrilobular necrosis, degranulation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum and mitochondrial abnormalities in rat liver 24 h after exposure. These pathological changes were accompanied by ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(81)90156-9
更新日期：1981-11-01 00:00:00
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journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90013-c
更新日期：1990-02-01 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：:The carcinogenicity of dichloromethane (DCM) has been demonstrated by mutagenicity studies using bacteria and yeasts and using animal bioassays. Epidemiological studies indicate that exposure to DCM increases the incidences of liver and pancreas cancers. In the present study, we determine whether DCM generates DNA dam...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.09.002
更新日期：2010-12-15 00:00:00
abstract：:A concern among hospital personnel is their exposure to mutagenic drugs and in the incidental exposures that could occur in caring for the patients. In a recent published study the mutagenicity of urine from patients administered antineoplastic drugs was determined and techniques were developed to chemically inactivat...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90049-5
更新日期：1988-03-01 00:00:00
abstract：:Chloropicrin is an aliphatic volatile nitrate compound that is mainly used as a pesticide. It has several toxic effects in animals and can cause irritating and other health problems in exposed humans. Since the mode of chloropicrin action is poorly understood, the aim of this study was to investigate molecular respons...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.04.002
更新日期：2012-06-20 00:00:00
abstract：:Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer - the skin's main barrier against xenobiotic penetratio...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2013.03.005
更新日期：2013-05-23 00:00:00
abstract：:A single, 50 mg/kg i.p. dose of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) to mice significantly inhibited glutathione reductase activity in liver within 10 min, and in lung and heart within 30 min. Maximal inhibition was reached at 4 h in all tissues and glutathione reductase activity remained significantly depress...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90036-x
更新日期：1983-06-01 00:00:00
abstract：:Mouse neuroblastoma cells exposed to 2.5 and 5.0 microM methylmercury for 24 h appeared rounded with the loss of processes. Immunohistochemical staining directed against beta-tubulin revealed severe alterations in microtubular architecture. Non-membrane-bound condensation product was visualized ultrastructurally in th...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90226-c
更新日期：1990-03-01 00:00:00
abstract：:Two groups, each of 4 rabbits, 17 and 4 months old, respectively, were given s.c. administrations of cadmium (Cd) at a dose level of 0.5 mg/kg/day 6 times per week for up to 32 weeks. In 17-month-old rabbits, low-molecular-weight proteinuria appeared in the 3rd week, proteinuria, glycosuria and anemia in the 6th week;...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(80)90123-x
更新日期：1980-09-01 00:00:00
abstract：:Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. However, in vivo studies in various, soman poisoned animal species showed a therapeutic effect of oximes, with the exac...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.10.005
更新日期：2018-09-01 00:00:00
