Toxicology

Endogenous Dopamine is Involved in the Herbicide Paraquat-Induced Dopaminergic Cell Death
The herbicide paraquat is an environmental factor that may be involved in the etiology of Parkinson disease. Systemic exposure of mice to paraquat causes a selective loss of dopaminergic neurons in the substantia nigra pars compacta, although paraquat is not selectively incorporated in dopaminergic neurons. Here, we report a contribution of endogenous dopamine to paraquat-induced dopaminergic c...


Cross-Linking of beta-Lactoglobulin Enhances Allergic Sensitization Through Changes in Cellular Uptake and Processing
Cross-linking of proteins has been exploited by the food industry to change food texture and functionality but the effects of these manipulations on food allergenicity still remain unclear. To model the safety assessment of these food biopolymers, we created cross-linked bovine β-lactoglobulin (CL-BLG) by laccase treatment. of the present study was to compare the immunogenicity and allerge...
Structures of Exocyclic R,R- and S,S-N6,N6-(2,3-Dihydroxybutan-1,4-diyl)-2′-Deoxyadenosine Adducts Induced by 1,2,3,4-Diepoxybutane
1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N6 position of adenine in DNA. Two enantiomers of bis-N6-dA adducts of DEB have been identified: R,R-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (...


Mechanism of an indirect effect of aqueous cigarette smoke extract on the adhesion of monocytic cells to endothelial cells in an in vitro assay revealed by transcriptomics analysis
The adhesion of monocytic cells to the “dysfunctional” endothelium constitutes a critical step in the initiation of atherosclerosis. Cigarette smoke (CS) has been shown to contribute to this process, the complex mechanism of which still needs to be unraveled. We developed an in vitro adhesion assay to investigate the CS-induced adhesion of monocytic MM6 cells to human umbilical vein endothe...
How useful are clinical liver function tests in in vitro human hepatotoxicity assays?
In preclinical hepatotoxicity testing cell based assays are frequently employed. However, prediction of clinical drug induced liver injury (DILI) remains a major challenge. Here we examined the usefulness of frequently employed markers of hepatocellular injury in cultures of primary human hepatocytes (PHH) in response to treatment with either paracetamol, rifampicin, petadolex and/or amiodarone...


Direct and indirect air particle cytotoxicity in human alveolar epithelial cells
Air particulate matter has been associated with adverse impact on the respiratory system leading to cytotoxic and proinflammatory effects. The biological mechanisms behind these associations may be initiated by inhaled small size particles, particle components (soluble fraction) and/or mediators released by particle-exposed cells (conditioned media). The effect of Urban Air Particles from Bueno...
Generation and Characterization of Gsuα:EGFP Transgenic Zebrafish for Evaluating Endocrine-Disrupting Effects
The glycoprotein subunit α (gsuα) gene encodes the shared α subunit of the three pituitary heterodimeric glycoprotein hormones: follicle-stimulating hormone β (Fshβ), luteinizing hormone β (Lhβ) and thyroid stimulating hormone β (Tshβ). In our current study, we identified and characterized the promoter region of zebrafish gsuα and generated a stable gsuα:EGFP transgenic line, which r...

Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors α and γ agonist, following oral administration to Sprague Dawley rats for 94-101 weeks
Ckd-501 is a peroxisome proliferator-activated receptor (PPAR) agonist. The current study was conducted in Sprague Dawley (SD) rats for 94–101 weeks to investigate the carcinogenic potential of CKD-5060 males received 0, 0.03, 0.12, or 1.0 mg/kg/day, which was changed after 66 weeks to 0.24 mg/kg/day due to increased mortality, while 60 females received 0, 0.03, 0.06, or 0.12 mg/kg/day throug...
Human Health Risk Assessment of Nitrosamines and Nitramines for potential application in CO2 capture
Emission and accumulation of carbon dioxide (CO2) in the atmosphere exert an environmental and climate change challenge. An attempt to deal with this challenge is made at Mongstad by application of amines for CO2 capture and storage (CO2 capture Mongstad (CCM) project). As part of the CO2 capture process, nitrosamines and nitramines may be emitted. Toxicological testing of nitrosamines and nitr...

Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats
To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats chall...
Bacteriological quality assessment of drinking water available at the flood affected areas of Peshawar
Monsoon flooding occurred in the main areas of the Khyber Pakhtunkhwa, Punjab, and Balochistan as well as parts of Gilgit Baltistan of Pakistan and Azad Jammu Kashmir in July 2010. Water-borne diseases such as cholera, enteric fever, and dysentery were common among the inhabitants of flood-affected areas which were selected for sample collection. In the present study, 10 sites in District Pesha...

Identification of a Novel Mutation in the Presenilin 1 Gene in a Chinese Alzheimer’s Disease Family
This study has identified a gene mutation in a Chinese family with Alzheimer’s disease (AD). Family members were screened by a set of medical examinations and neuropsychological tests. Their DNA was extracted from blood cells and sequenced for gene mutation in the amyloid precursor protein (APP), the presenilin 1 (PS1) and the presenilin 2 (PS2) genes. Genetic analysis showed that the AD pati...
Antidepressant and Antioxidative Effect of Ibuprofen in the Rotenone Model of Parkinson’s Disease
Idiopathic Parkinson’s disease is a neurodegenerative disorder that affects approximately 1 % of the population over 55 years of age. The disease manifests itself through motor and nonmotor symptoms induced mainly by the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The possible mechanisms involved in this pathology include mitochondrial dysfunction...
PACAP Protects Against Inflammatory-Mediated Toxicity in Dopaminergic SH-SY5Y Cells: Implication for Parkinson’s Disease
There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson’s disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown to possess neurotrophic as well as neuroprotective properties. In this study...
Acute Methotrexate Ingestions in Adults: A Report of Serious Clinical Effects and Treatments
Limited reported data have reports effects after acute ingestion of methotrexate. Treatment recommendations do not differentiate between exposure routes. Our objective was to determine the frequency of significant toxicity effects and use of therapy after methotrexate ingestion in adults. Methods. We performed a retrospective study on adult cases reported to 6 poison centers over 6 years (2000...