Parallelogram approach using rat-human In vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans

The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...

Genomic diversity within the enterobacter cloacae complex

Background: Isolates of the Enterobacter cloacae complex have been increasingly isolated as nosocomial pathogens, but phenotypic identification of the E. cloacae complex is unreliable and irreproducible. Identification of species based on currently available genotyping tools is already superior to phenotypic identification, but the taxonomy of...

Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents. II. Neurobehavioral effects of white spirit in rat and human

To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in...

Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

Aims/hypothesis: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods: Chronic hepatic steatosis and hepatic insulin resistance were...

Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents. I. Validation of methods with ethanol

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to...

Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice

The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma. Whereas LDLR deficiency in mice results in the...

Embryotoxicity and teratogenicity study with α-cyclodextrin in rabbits

In a standard embryotoxicity/teratogenicity study, α-cyclodextrin (α-CD) was administered to groups of sixteen, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. An additional group received a diet containing 20% lactose. Treatment started on day 0 of gestation and ended on day 29 when the animals...

Disposition of 14C-α-cyclodextrin in germ-free and conventional rats

The absorption, disposition, metabolism, and excretion of uniformly 14C-labeled α-cyclodextrin (14C-α-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, 14C-α-CD (25μCi, 50mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, 14C-α-CD (25μCi, 200mg/kg bw) was given...

Embryotoxicity and teratogenicity study with α-cyclodextrin in rats

The embryotoxicity/teratogenicity of α-cyclodextrin (α-CD) was examined in Wistar Crl:(WI)WU BR rats. α-CD was fed at dietary concentrations of 0, 1.5, 5, 10, or 20% to groups of 25 pregnant female rats from day 0 to 21 of gestation. An additional group received a diet with 20% lactose. The additions to the diet of α-CD and lactose were made at...

Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats

Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of rats fed the HFFO diets compared with rats fed...

Long-term, low-level exposure of guinea pigs and marmosets to sarin vapor in air: Lowest observable effect level

Realistic scenarios for low-level exposure to nerve agents will often involve exposures over several hours to extremely low doses of agent. In order to expose animals to the lowest controllable concentrations of agent and to increase exposure times until a lowest observable effect level (LOEL) becomes measurable, a validated system was developed...

Cell culture techniques in biotransformation studies

The use of liver cell cultures derived from different mammalian species in in vitro toxicological studies: implementation in extrapolation models?

In vitro techniques can be applied to obtain insight into the organotoxic potential of compounds and in the underlying mechanisms of action. During the last few decades the applicability of these techniques in toxicology has been demonstrated for an increasing number of cell types. Cultured hepatocytes have been shown to provide convenient in...