Paradoxical patterns of sinusoidal obstruction syndrome-like liver injury in aged female CD-1 mice triggered by cannabidiol-rich cannabis extract and acetaminophen co-administration

Authors

Laura E. Ewing, University of Arkansas for Medical Sciences
Mitchell R. McGill, University of Arkansas for Medical Sciences
Eric U. Yee, University of Arkansas for Medical Sciences
Charles M. Quick, University of Arkansas for Medical Sciences
Charles M. Skinner, University of Arkansas for Medical Sciences
Stefanie Kennon-McGill, University of Arkansas for Medical Sciences
Melissa Clemens, University of Arkansas for Medical Sciences
Joel H. Vazquez, University of Arkansas for Medical Sciences
Sandra S. McCullough, University of Arkansas for Medical Sciences
D. Keith Williams, University of Arkansas for Medical Sciences
Kristy R. Kutanzi, University of Arkansas for Medical Sciences
Larry A. Walker, University of Mississippi School of Pharmacy
Mahmoud A. ElSohly, University of Mississippi School of Pharmacy
Laura P. James, University of Arkansas for Medical Sciences
Bill J. Gurley, University of Arkansas for Medical Sciences
Igor Koturbash, University of Arkansas for Medical Sciences

Document Type

Article

Publication Date

6-17-2019

Abstract

© 2019 The Authors. Environmental Toxicology published by Wiley Periodicals, Inc. Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.

Relational Format

journal article

Recommended Citation

Ewing, L. E., McGill, M. R., Yee, E. U., Quick, C. M., Skinner, C. M., Kennon-McGill, S., Clemens, M., Vazquez, J. H., McCullough, S. S., Williams, D. K., Kutanzi, K. R., Walker, L. A., ElSohly, M. A., James, L. P., Gurley, B. J., & Koturbash, I. (2019). Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration. Molecules, 24(12), 2256. https://doi.org/10.3390/molecules24122256

DOI

10.3390/molecules24122256