Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI
Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure—a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/10/2/56 |
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| author | DeAunne Denmark Ilene Ruhoy Bryan Wittmann Haleh Ashki Lorrin M. Koran |
| author_facet | DeAunne Denmark Ilene Ruhoy Bryan Wittmann Haleh Ashki Lorrin M. Koran |
| author_sort | DeAunne Denmark |
| collection | DOAJ |
| description | Despite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure—a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals (<i>n</i> = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended. |
| first_indexed | 2024-03-09T20:56:33Z |
| format | Article |
| id | doaj.art-8af0b64191f54bbf9269db476df39a63 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-09T20:56:33Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-8af0b64191f54bbf9269db476df39a632023-11-23T22:20:07ZengMDPI AGToxics2305-63042022-01-011025610.3390/toxics10020056Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRIDeAunne Denmark0Ilene Ruhoy1Bryan Wittmann2Haleh Ashki3Lorrin M. Koran4Department of Behavioral Neuroscience, Oregon Health & Science University, 3710 SW US Veterans Hospital Road, Mail Code R&D40, Portland, OR 97239, USAMount Sinai South Nassau Chiari-EDS Center, 1420 Broadway, Hewlett, NY 11557, USAOwlstone Medical, 600 Park Offices Drive, Suite 140, Research Triangle Park, NC 27709, USAPrime Genomics, Inc., 319 Bernardo Avenue, Mountain View, CA 94041, USADepartment of Psychiatry and Behavioral Sciences, OCD Clinic, Stanford University Medical Center, 401 Quarry Road, Stanford, CA 94305, USADespite the impressive safety of gadolinium (Gd)-based contrast agents (GBCAs), a small number of patients report the onset of new, severe, ongoing symptoms after even a single exposure—a syndrome termed Gadolinium Deposition Disease (GDD). Mitochondrial dysfunction and oxidative stress have been repeatedly implicated by animal and in vitro studies as mechanisms of Gd/GBCA-related toxicity, and as pathogenic in other diseases with similarities in presentation. Here, we aimed to molecularly characterize and explore potential metabolic associations with GDD symptoms. Detailed clinical phenotypes were systematically obtained for a small cohort of individuals (<i>n</i> = 15) with persistent symptoms attributed to a GBCA-enhanced MRI and consistent with provisional diagnostic criteria for GDD. Global untargeted mass spectroscopy-based metabolomics analyses were performed on plasma samples and examined for relevance with both single marker and pathways approaches. In addition to GDD criteria, frequently reported symptoms resembled those of patients with known mitochondrial-related diseases. Plasma differences compared to a healthy, asymptomatic reference cohort were suggested for 45 of 813 biochemicals. A notable proportion of these are associated with mitochondrial function and related disorders, including nucleotide and energy superpathways, which were over-represented. Although early evidence, coincident clinical and biochemical indications of potential mitochondrial involvement in GDD are remarkable in light of preclinical models showing adverse Gd/GBCA effects on multiple aspects of mitochondrial function. Further research on the potential contributory role of these markers and pathways in persistent symptoms attributed to GBCA exposure is recommended.https://www.mdpi.com/2305-6304/10/2/56gadolinium-based contrast agents (GBCAs)gadoliniummitochondrial diseasemetabolomicsoxidative stress |
| spellingShingle | DeAunne Denmark Ilene Ruhoy Bryan Wittmann Haleh Ashki Lorrin M. Koran Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI Toxics gadolinium-based contrast agents (GBCAs) gadolinium mitochondrial disease metabolomics oxidative stress |
| title | Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI |
| title_full | Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI |
| title_fullStr | Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI |
| title_full_unstemmed | Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI |
| title_short | Altered Plasma Mitochondrial Metabolites in Persistently Symptomatic Individuals after a GBCA-Assisted MRI |
| title_sort | altered plasma mitochondrial metabolites in persistently symptomatic individuals after a gbca assisted mri |
| topic | gadolinium-based contrast agents (GBCAs) gadolinium mitochondrial disease metabolomics oxidative stress |
| url | https://www.mdpi.com/2305-6304/10/2/56 |
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