Showing papers in "Toxicology and Applied Pharmacology in 2010"

TL;DR: The results indicate that Ag NPs in D. melanogaster induce heat shock stress, oxidative stress, DNA damage and apoptosis, which suggests that the organism is stressed and thus warrants more careful assessment ofAg NPs using in vivo models to determine if chronic exposure presents developmental and reproductive toxicity.

TL;DR: Overall, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer, and there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients.

TL;DR: In conclusion, switching on and off of Nrf2 combined with promoting an auto-regulatory loop between them regulates activation/deactivation of defensive genes leading to protection of cells against adverse effects of oxidative and electrophilic stress and promote cell survival.

TL;DR: Because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of NRF2 on the kinetics of drugs and other Xenobiotics should also be considered, with a special emphasis on metabolism and Excretion.

TL;DR: The example of Aristolochia and aristolochic acids is used to highlight the challenges related to safety assessment, and the opportunities that exist to more accurately elucidate the toxicity of herbal medicines.

TL;DR: This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H(2)O(2), act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells and proposed cellular adaptive response to oxidative stress challenge.

TL;DR: A luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes and results indicate a good predictive value of this approach for hazard identification.

TL;DR: Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

TL;DR: The experimental data show that oxidative stress may be a key route in inducing the cytotoxicity of ZnO nanoparticles in colon carcinoma cells, and the study of the relationship between toxicological effects and physico-chemical characteristics of particles suggests that surface area does not play a primary role in the cyttoxicity.

TL;DR: In this article, the authors performed a kinetic study in mice with different sizes of PEG-coated gold nanoparticles and found that small AuNPs transiently activated CYP1A1 and 2B, phase I metabolic enzymes, in liver tissues from 24h to 7 days, which mirrored with elevated gold levels in the liver.

TL;DR: The data suggest that the JNK inhibitor SP600125 protects against APAP-induced liver injury in part by attenuation of mitochondrial Bax translocation but mainly by preventing mitochondrial oxidant stress and peroxynitrite formation and thereby preventing the mitochondrial permeability transition pore opening, a key event in APAP -induced cell necrosis.

TL;DR: The functions of Nrf2 suggest a hormetic factor that has evolved empirically over time based on environmental and oxidative challenge, while highlighting the versatility and protective abilities elicited upon activation.

TL;DR: The role of Nrf2 in airways is addressed based on emerging evidence from experimental oxidative disease models and human studies and association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 andNRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRf2 in these lung diseases.

TL;DR: The metabolomics platform is reviewed with particular emphasis on applications involving drug-induced hepatotoxicity and nephrotoxicity, with emphasis on recent work in the field.

TL;DR: NPs accumulated within bile canaliculi to a limited extent, which suggests that NPs can be eliminated within biles, in keeping with the finding that gold NPs were eliminated in bile following intravenous injection into rats.

TL;DR: By adaptively upregulating antioxidant enzymes, oxidative stress may inadvertently attenuate ROS signals that mediate physiological processes, resulting in aberrations of cellular functions and adverse consequences, and the premise that dietary antioxidant supplements is generally beneficial to human health is re-examine.

TL;DR: The intracellular ROS generation and cytokine production induced cytotoxicity point towards the mechanistic pathway of cell death upon exposure to PAMAM dendrimers.

TL;DR: Data derived from cell-based studies and knockout mice are reviewed in an attempt to define the role and regulation of Nrf1 in oxidative stress response and other functions.

TL;DR: No adverse effects from gold NPs were observed in a triple cell co-culture model simulating the alveolar lung epithelium, and chronic studies under in vivo conditions are needed to entirely exclude adverse effects.

TL;DR: This study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems, and augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gbeta1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress.

TL;DR: The initial data shows that this platform is a robust alternative to animal and other in vitro models for the prediction of the developmental toxicity of chemicals that may also provide invaluable information about the underlying biochemical pathways.

TL;DR: Due to the high sensitivity of human hepatocytes and currently MCLR-only based risk calculations, the actual risk of human MC-intoxication and ensuing liver damage could be underestimated in freshwater cyanobacterial blooms where MCLW and-LF predominate.

TL;DR: It was shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenum status.

TL;DR: The purpose of this paper is to review the head and neck tract cancer-related data on exposure to heavy metals via smoking and working exposure and to study the major mechanisms underlying some toxic metals carcinogenesis.

TL;DR: A dual toxicological effect of DON is demonstrated on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and a possible link between them through diminished synthesis of the tight junction constituent claudin-4 is suggested.

TL;DR: Observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

TL;DR: It is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity.

TL;DR: A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort to verify that automated measurements were comparable to those of traditional observational studies.

TL;DR: It is demonstrated that SMN reduced, delayed onset, or prevented toxic effects of Dox which are typically associated with hydroxyl radical production, and performed as an antioxidant limiting oxidative stress, and raised the possibility that such protection may extend to other organs during Dox treatment including the heart.

TL;DR: An iron chelator, desferrioxamine, suppressed all the above Ferucarbotran-induced actions, demonstrating an important role of free iron in the inhibition of osteogenic differentiation that is mediated by the promotion of cell mobilization, involving the activation of a specific signaling pathway.