Investigation of potential adverse central nervous system effects after long term oral administration of gadolinium in mice.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Central Nervous System/*drug effects ; Gadolinium/*administration & dosage ; Gadolinium/*adverse effects; Administration, Oral ; Animals ; Female ; Locomotion/drug effects ; Mice ; Mice, Inbred C57BL

Objectives: To examine potential gadolinium (Gd) accumulation in the brain of healthy mice after long-term oral administration of Gd-containing food pellets and to investigate whether Gd leads to adverse central nervous system (CNS) effects, specifically focussing on locomotor impairment in Gd exposed compared to control animals.
Materials and Methods: The local Animal Experimental Ethics Committee approved all procedures and applications. Fifteen female C57Bl/6 mice were orally exposed to a daily intake of 0.57 mmol Gd chloride/ kg body weight over a period of 90 weeks from the age of 4 weeks on. Gd-free, but otherwise equivalent experimental diets were given to the control group (N = 13). The animals were monitored daily by animal caretakers regarding any visible signs of distress and evaluated clinically every four weeks for the first 60 weeks and afterwards every two weeks for a better temporal resolution of potential long-term effects regarding impairment of motor performance and loss of body weight. The individual Gd content was measured using mass spectrometry in a sub-cohort of N = 6 mice.
Results: The absolute brain Gd levels of the Gd-exposed mice were significantly increased compared to control mice (0.033± 0.009 vs. 0.006± 0.002 nmol Gd/ g brain tissue). Long-term oral Gd exposure over almost the entire life-span did not lead to adverse CNS effects including locomotor changes (rotarod performance, p = 0.1467) in healthy mice throughout the study period. Gd-exposed mice showed less increased body weight compared to control mice during the study period (p = 0.0423). Histopathological alterations, such as hepatocellular vacuolization due to fatty change in the liver and a loss of nucleated cells in the red pulp of the spleen, were found in peripheral organs of both groups.
Conclusions: Low levels of intracerebral Gd caused by chronic oral exposure over almost the entire life span of mice did not lead to alterations in locomotor abilities in healthy mice throughout the normal aging process.
Competing Interests: T.F. und H.P. are employees of Bayer AG and are currently conducting research sponsored by this company. For our study, T.F. and H.P. contributed primarily to the methodology of intracerebral Gd measurements by ICP-MS. The research is, however, not financially supported by industry. The commercial affiliation to Bayer AG does not alter our adherence to PLOS ONE policies on sharing data and materials.

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AU0V1LM3JT (Gadolinium)

Date Created: 20200424 Date Completed: 20200713 Latest Revision: 20200713

20240105

PMC7179865

10.1371/journal.pone.0231495

32324769