Potential toxicity evaluation and comparison within multiple mice organs after repeat injections of linear versus macrocyclic gadolinium-based contrast agents: A comprehensive and time course study. (10th October 2021)

• Record Type: Journal Article
• Authors: Kong, Ying; Zhang, Shuai; Wang, Jiali; Han, Cuiping; Yu, Nana; Liu, Qi; Wang, Wentao; Xu, Kai
• Is Part Of: Toxicology letters. Volume 350(2021)
• Page Start: 152
• Page End: 161
• Publication Date: 2021-10-10
• Subjects: GBCAs gadolinium-based contrast agents -- NFS nephrogenic systemic fibrosis -- DCN deep cerebellar nuclei -- GP globus pallidus -- PWL paw withdraw latency -- PWT paw withdrawal threshold -- ICP-MS inductively coupled plasma-mass spectrometry -- TEM transmission electron microscopy -- WBC white blood cells -- RBC red blood cells -- HGB hemoglobin -- HCT hematocrit -- MCV mean corpuscular volume -- MCH mean corpuscular hemoglobin volume -- MCHC mean corpuscular hemoglobin concentration -- PLT platelet -- TP total protein -- ALB albumin -- ALT alanine aminotransferase -- AST aminotransferase -- UREA serum urea nitrogen -- CERA serum creatinine; Gadolinium-based contrast agents -- Multiple-organ/tissue -- Toxicity evaluation -- Time course; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2021.07.016
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs. In most case, linear GBCAs show faster accumulation and regression speed in examined tissues than macrocyclic GBCAs. Linear GBCAs can evoke transient increase of heat hyperalgesia and white blood cells. Gadodiamide can cause reversible vacuolar changes in the renal tubular epithelial cells. Long-term injection of gadodiamide induces severe skin lesion in mice tail. Abstract: As nephrogenic systemic fibrosis (NSF) and increased signal intensities in deep cerebellar nuclei (DCN) were successively discovered in renal insufficiency patients and healthy persons after gadolinium-based contrast agents (GBCAs) exposure, an awareness of potential toxicity with GBCAs exposure has been heightening. Herein, we performed a multi-organ/tissue toxicity assessment after different GBCAs administration with a large number of samples, and long-term, time-course schedule investigation. ICR mice were randomized to five exposure groups (n = 42/group) and received intravenous injection of GBCAs (2.5 mmol Gd/kg) or saline four time a week for 5 consecutive weeks. Gadolinium concentration detection, sensory tests, histological and hematological analyses were performed at corresponding timepoints (4th or 6th or 10th week). Our results showed that (i) gadodiamide could cause reversible vacuolar changes in the renal tubular epithelial cells, which appeared at 6th week and recovered at 10th week, and severe skin lesion in mice tail with consecutive injection for 10 weeks, that (ii) linear GBCAs (gadodiamide and gadopentetate dimeglumine) markedly elevated heat hyperalgesia and white blood cells of mice at 6th week and most of these changes could recovery at 10th week, and that (iii) linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs and in most case, linear GBCAs showed faster accumulation and regression speed in examined tissues than macrocyclic GBCAs excepting gadodiamide in skin which showed slowest regression speed. Collectively, macrocyclic GBCAs presents more stable, lower propensity to release Gd and safer profiles versus linear GBCAs.