Toxicology

Hippocampal ER stress and learning deficits following repeated pyrethroid exposure
Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3...


Application of high-throughput sequencing to circulating microRNAs reveals novel biomarkers for drug-induced liver injury
Drug-induced liver-injury (DILI) is a leading cause of acute liver failure and the major reason for withdrawal of drugs from the market. Preclinical evaluation of drug candidates has failed to detect about 40% of potentially hepatotoxic compounds in humans. At the onset of liver injury in humans, currently used biomarkers have difficulty differentiating severe DILI from mild, and/or predict the...
Central IKKß inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes
Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (...


Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection
Exposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity. Neonatal mic...
Role of Calcium and Calpain in the Downregulation of Voltage-Gated Sodium Channel Expression by the Pyrethroid Pesticide Deltamethrin
Voltage-gated sodium channels (Nav) are essential for initiation and propagation of action potentials. Previous in vitro studies reported that exposure to the Nav toxins veratridine and α scorpion toxin cause persistent downregulation of Nav mRNA in vitro. However the mechanism of this downregulation is not well characterized. Here, we report that the type-II pyrethroid deltamethrin, which has...


Poisoning by Ipomoea asarifolia in lambs by the ingestion of milk from ewes that ingest the plant
Two experiments, each with 10 pregnant ewes (8 treated and 2 controls) were performed to determine if nursing lambs of lactating ewes become intoxicated when the ewes ingest Ipomoea asarifolia but do not show clinical signs themselves. In the first experiment the sheep grazed I. asarifolia in the field while in the second, sheep were maintained in individual bays consuming dry I. asarifolia at ...
Epithelium specific ETS transcription factor, ESE-3, of Protobothrops flavoviridis snake venom gland transactivates the promoters of venom phospholipase A2 isozyme genes
Protobothrops flavoviridis (habu) (Crotalinae, Viperidae) is a Japanese venomous snake, and its venom contains the enzymes with a variety of physiological activities. The phospholipases A2 (PLA2s) are the major components and exert various toxic effects. They are expressed abundantly in the venom gland. It is thought that the venom gland-specific transcription factors play a key role for activa...

Optimal Allocation of Cell-Phone and Landline Respondents in Dual-Frame Surveys
Dual-frame telephone surveys that sample from both landline and cell-phone frames have become common because the US population is increasingly abandoning landline phones. Designing a dual-frame telephone survey requires a decision on the sample allocation, and ultimately the allocation of respondents, from each of the two frames. The allocation of the sample to the two frames influences the une...
Evaluation of Levodopa and Carbidopa Antioxidant Activity in Normal Human Lymphocytes In Vitro: Implication for Oxidative Stress in Parkinson’s Disease
The main pathochemical hallmark of Parkinson’s disease (PD) is the loss of dopamine in the striatum of the brain, and the oral administration of levodopa (l-dopa) is a treatment that partially restores the dopaminergic transmission. In vitro assays have demonstrated both toxic and protective effects of l-dopa on dopaminergic cells, while in vivo studies have not provided any convincing data. ...

Acute Toxicity of Subcutaneously Administered Vitamin E Isomers Delta- and Gamma-Tocotrienol in Mice
The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection si...
Toxicodynamic and Toxicokinetic Descriptors of Combined Chromium (VI) and Nickel Toxicity
After repeated intraperitoneal injections of nickel and chromium (VI) salts to rats, we found, and confirmed by mathematical modeling, that their combined subchronic toxicity can either be of additive type or depart from it (predominantly toward subadditivity) depending on the effect assessed. Against the background of moderate systemic toxicity, the combination under study proved to possess a ...

The sub-chronic oral toxicity of dearomatized hydrocarbon solvents in Sprague–Dawley rats
Dearomatized hydrocarbon solvents in the C9–C14 aliphatic carbon number range were developed as alternatives to traditional solvents such as mineral spirits, but with lower aromatic content. Previous subchronic toxicity studies (both published and unpublished) have shown minimal to no systemic effects with exposure to dearomatized solvents, with the exception of rat-specific renal effects tha...
Toxicological assessment of kretek cigarettes. Part 7: The impact of ingredients added to kretek cigarettes on inhalation toxicity
The biological activity of mainstream smoke from experimental kretek cigarettes with and without three mixes of ingredients was assessed in a 90-day rat inhalation study and in a 4-day in vivo micronucleus assay. 350 ingredients, commonly used in various combinations and in a limited number in a given brand in the manufacture of marketed kretek cigarettes, were applied at a low and a high targe...
Hep-2 cell based indirect immunofluorescence assay for antinuclear antibodies as a potential diagnosis of drug-induced autoimmunity in nonclinical toxicity testing
Antinuclear antibodies (ANAs) are important biomarkers in the diagnosis of autoimmune diseases in humans; however, the diagnostic performance of ANA in nonclinical safety studies are not well understood. Here, we studied the use of ANAs as potential nonclinical biomarkers for drug-induced autoimmunity (DIA) using a Hep-2 based indirect immunofluorescence assay (IFA). Initially, MRL-faslpr/J mic...
Purification, characterization and anti-diabetic activity of a polysaccharide from mulberry leaf
In the present study, a high-purity polysaccharide from mulberry leaf (MLP) was purified and characterized, and its anti-diabetic effects were investigated in streptozotocin (STZ)-induced diabetic rats. Our results showed that the obtained MLP (purity 99.8%) was determined to be composed of d-arabinose, d-xylose, d-glucose, d-rhamnose and d-mannose with molar ratio of 1:2.13:6.53:1.04:8.73. Ora...