Prevention of Simvastatin-Induced Inhibition of Tendon Cell Proliferation and Cell Cycle Progression by Geranylgeranyl Pyrophosphate
Statins have been reported to induce tendinopathy and even tendon rupture. The present study was designed to investigate the potential molecular mechanism underlying the adverse effect of simvastatin on tendon cells. An in vitro tendon healing model was performed using tendon cells isolated from rat Achilles tendons. The viability of tendon cells and cell cycle progression were examined by the MTT assay and flow cytometric analysis, respectively. Immunofluorescent staining for Ki-67 was used to assess the proliferation activity of tendon cells. Western blot analysis and coimmunoprecipitation was used to determine the ...
Source: Toxicological Sciences - January 25, 2016 Category: Toxicology Authors: Tsai, W.-C., Yu, T.-Y., Lin, L.-P., Cheng, M.-L., Chen, C.-L., Pang, J.-H. S. Tags: Mitigation of Statin Adverse Effects by Isoprenoid Derivatives Source Type: research
Dose and Effect Thresholds for Early Key Events in a PPAR{alpha}-Mediated Mode of Action
Current strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di (2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP)...
Source: Toxicological Sciences - January 25, 2016 Category: Toxicology Authors: Lake, A. D., Wood, C. E., Bhat, V. S., Chorley, B. N., Carswell, G. K., Sey, Y. M., Kenyon, E. M., Padnos, B., Moore, T. M., Tennant, A. H., Schmid, J. E., George, B. J., Ross, D. G., Hughes, M. F., Corton, J. C., Simmons, J. E., McQueen, C. A., Hester, S Tags: Thresholds of Key Events in PPAR[alpha ] Mode of Action Source Type: research
2,3',4,4',5-Pentachlorobiphenyl Induces Inflammatory Responses in the Thyroid Through JNK and Aryl Hydrocarbon Receptor-Mediated Pathway
In this study, we explored the influences of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on inflammatory responses and its underlying mechanisms in the thyroid. Wistar rats were administered PCB118 intraperitoneally at 0, 10, 100, and 1000 μg/kg/d, 5 days a week for 13 weeks; rat thyroid FRTL-5 cells were treated with PCB118 (0, 0.25, 2.5, and 25 nM) for indicated time. Results revealed that PCB118 promoted the generation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) in a time- and dose-related manner and decreased sodium/iodide symporter (NIS) protein ...
Source: Toxicological Sciences - January 25, 2016 Category: Toxicology Authors: Xu, B., Yang, H., Sun, M., Chen, H., Jiang, L., Zheng, X., Ding, G., Liu, Y., Sheng, Y., Cui, D., Duan, Y. Tags: PCB-Induced Thyroid Dysfunction Signaling Source Type: research
Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells
Our previously published data show that As+3 in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As+3 metabolite, monomethylarsonous acid (MMA+3), was responsible for the observed pre-B cell toxicity caused by As+3. Interleukin-7 (IL-7) is the primary growth factor responsible for pre-lymphoid development in mouse and human bone marrow, and Signal Transducer and Activator of Transcription 5 (STAT5) is a transcriptional factor in the IL-7 signaling pathway. We found that MMA+3 inhibited STAT5 phosphorylation at a c...
Source: Toxicological Sciences - January 25, 2016 Category: Toxicology Authors: Ezeh, P. C., Xu, H., Lauer, F. T., Liu, K. J., Hudson, L. G., Burchiel, S. W. Tags: Immunotoxicity of Trivalent Arsenic Species Source Type: research
Elevated Lifetime Lead Exposure Impedes Osteoclast Activity and Produces an Increase in Bone Mass in Adolescent Mice
This study accentuates the dose dependent variation in Pb exposure and consequent effects on skeletal health. (Source: Toxicological Sciences)
Source: Toxicological Sciences - January 25, 2016 Category: Toxicology Authors: Beier, E. E., Holz, J. D., Sheu, T.-J., Puzas, J. E. Tags: Lead Exposure and Bone Homeostatis Source Type: research
