From the Cover: Comparative Numerical Modeling of Inhaled Nanoparticle Deposition in Human and Rat Nasal Cavities
This study bridges the in vitro exposure experiments and in vivo nanomaterials toxicity studies, and can contribute towards improving inter-species exposure extrapolation studies in the future. (Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Dong, J., Shang, Y., Inthavong, K., Tu, J., Chen, R., Bai, R., Wang, D., Chen, C. Tags: Modeling of Nanoparticles in Nasal Cavities Source Type: research
Editor's Highlight: Plasma miR-183/96/182 Cluster and miR-124 are Promising Biomarkers of Rat Retinal Toxicity
Retinal toxicity is one of the leading causes of attrition in drug development, and drug-induced retinal toxicity remains an issue in both drug discovery and postmarketed drugs. Derisking strategies to help with early identification of retinal injury utilizing a predictive retinal miRNA biomarker would greatly benefit decision-making in drug discovery programs, ultimately reducing attrition due to retinal toxicity. Our previous work demonstrated elevation of circulating retina-enriched miRNAs in a retinal toxicity model. To further validate our previous observation, 2 additional rat retinal injury models were utilized in t...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Peng, Q., Collette, W., Giddabasappa, A., David, J., Twamley, M., Kalabat, D., Aguirre, S. A., Huang, W. Tags: MicroRNA Biomarkers for Retinal Toxicity Source Type: research
MicroRNA Biomarkers of Toxicity in Biological Matrices
Biomarker measurements that reliably correlate with tissue injury and that can be measured within accessible biofluids offer benefits in terms of cost, time, and convenience when assessing chemical and drug-induced toxicity in model systems or human cohorts. MicroRNAs (miRNAs) have emerged in recent years as a promising new class of biomarker for monitoring toxicity. Recent enthusiasm for miRNA biomarker research has been fueled by evidence that certain miRNAs are cell-type specific and are released during injury, thus raising the possibility of using biofluid-based miRNAs as a "liquid biopsy" that may be obtained by sampl...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Harrill, A. H., McCullough, S. D., Wood, C. E., Kahle, J. J., Chorley, B. N. Tags: Editorials, Look Inside ToxSci, & Special Content Contemporary Review: Review of MicroRNA Biomarkers Source Type: research
Three Years After
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Miller, G. W. Tags: Editorials, Look Inside ToxSci, & Special Content Source Type: research
From the Editors Desk, Editors Highlights, Letters to the Editor
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Tags: Editorials, Look Inside ToxSci, & Special Content Source Type: research
Table of Contents
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Subscriptions
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Editorial Board
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Tags: Standing Material Source Type: research
Cover
(Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Tags: Cover Source Type: research
Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben
In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylp...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Boberg, J., Axelstad, M., Svingen, T., Mandrup, K., Christiansen, S., Vinggaard, A. M., Hass, U. Tags: Perinatal Butylparaben Perturbs Endocrine Function Source Type: research
Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards
In this study, the framework was applied to estimate MOEs for chemicals that can potentially cause developmental toxicity following a putative AOP for fetal vasculogenesis/angiogenesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe chemical disposition during pregnancy, fetal, neonatal, and infant to adulthood stages. Using this life-stage PBPK model, maternal exposures were estimated that would yield fetal blood levels equivalent to the chemical concentration that altered in vitro activity of selected HTS assays related to the most sensitive vasculogenesis/angiogenesis putative AOP. The re...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: El-Masri, H., Kleinstreuer, N., Hines, R. N., Adams, L., Tal, T., Isaacs, K., Wetmore, B. A., Tan, Y.-M. Tags: Integration of PBPK and AOPs for Environmental Hazard Assessment Source Type: research
Human Upcyte Hepatocytes: Characterization of the Hepatic Phenotype and Evaluation for Acute and Long-Term Hepatotoxicity Routine Testing
The capacity of human hepatic cell-based models to predict hepatotoxicity depends on the functional performance of cells. The major limitations of human hepatocytes include the scarce availability and rapid loss of the hepatic phenotype. Hepatoma cells are readily available and easy to handle, but are metabolically poor compared with hepatocytes. Recently developed human upcyte hepatocytes offer the advantage of combining many features of primary hepatocytes with the unlimited availability of hepatoma cells. We analyzed the phenotype of upcyte hepatocytes comparatively with HepG2 cells and adult primary human hepatocytes t...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Tolosa, L., Gomez-Lechon, M. J., Lopez, S., Guzman, C., Castell, J. V., Donato, M. T., Jover, R. Tags: Upcyte Hepatocytes for Toxicity Testing Source Type: research
Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21, -200c, and -423
Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD pa...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Pavkovic, M., Robinson-Cohen, C., Chua, A. S., Nicoara, O., Cardenas-Gonzalez, M., Bijol, V., Ramachandran, K., Hampson, L., Pirmohamed, M., Antoine, D. J., Frendl, G., Himmelfarb, J., Waikar, S. S., Vaidya, V. S. Tags: Urinary microRNA Biomarkers of Acute Kidney Injury Source Type: research
Copper Exposure Perturbs Brain Inflammatory Responses and Impairs Clearance of Amyloid-Beta
Copper promotes a toxic buildup of amyloid-beta (Aβ) and neurofibrillary tangle pathology in the brain, and its exposure may increase the risk for Alzheimer’s disease (AD). However, underlying molecular mechanisms by which copper triggers such pathological changes remain largely unknown. We hypothesized that the copper exposure perturbs brain inflammatory responses, leading to impairment of Aβ clearance from the brain parenchyma. Here, we investigated whether copper attenuated Aβ clearance by microglial phagocytosis or by low-density lipoprotein-related receptor protein-1 (LRP1) dependent transcytosis ...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Kitazawa, M., Hsu, H.-W., Medeiros, R. Tags: Impaired Amyloid-Beta Clearance in Copper-Exposed Tissues Source Type: research
Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies
Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daik...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Hattori, Y., Naito, M., Satoh, M., Nakatochi, M., Naito, H., Kato, M., Takagi, S., Matsunaga, T., Seiki, T., Sasakabe, T., Suma, S., Kawai, S., Okada, R., Hishida, A., Hamajima, N., Wakai, K. Tags: Metallothionein Polymorphisms in Diabetes and Renal Disease Source Type: research
