Abstract: PO2232
Pathophysiological Insult of the Liver by Gadolinium-Based Contrast Agent Treatment
Session Information
- Pathology and Lab Medicine: Basic
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1601 Pathology and Lab Medicine: Basic
Authors
- Deaguero, Joshua, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Howard, Tamara A., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Wagner, Brent, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Escobar, G. Patricia, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Group or Team Name
- Kidney Institute of New Mexico
Background
The advent and overuse of gadolinium-based contrast agents (GBCAs) lead to consequent iatrogenic systemic fibrosis. Gadolinium may accumulate in tissues in every organ. GBCA treatment induces dyslipidemia and insulin resistance (Do C et al, Toxicol Appl Pharmacol 2019 Jul 15;375: 32-45). Therefore, the impact of gadolinium on the liver was investigated.
Methods
Wild-type male and female C57/BL6 mice were randomized by age and weight to untreated (n = 20) or GBCA-treatment (n = 20) (Omniscan, 2.5mmol/kg, intraperitoneally, 20 doses over 4 weeks). Tissue were isolated, specimens fixed in glutaraldehyde or snap frozen in liquid nitrogen. Metabolites were profiled by capillary electrophoresis mass spectrometry (Human Metabolome Technologies, Japan).
Results
Liver from the GBCA group demonstrated ballooned hepatocytes, lipid-laden vacuoles, and reduction in glycogen. Furthermore, GBCA treatment promoted hepatic steatosis. Gadolinium reduced expression of lipid metabolism and transport metabolites g-butyrobetaine, prostaglandin E2, O-acetylcarnitine, malonylcarnitine, isobutyryl CoA divalent, hexanoic acid, lauroylcarnitine, and decanoic acid (P < 0.05). GBCA treatment alters metabolite expression of metabolites from other pathways, including glycolysis, histidine metabolism, and purine metabolism. Furthermore, gadolinium treatment altered the urea cycle.
Conclusion
GBCA treatment alters several metabolic pathways, particularly lipid metabolism and lipid transport pathway intermediates. GBCA treatment induces ultrastructural and metabolic disruptions that mimic nonalcoholic fatty liver disease. These studies are the first to demonstrate GBCA mediates metabolic perturbations in the liver. GBCAs are not biologically inert.
Funding
- NIDDK Support
