Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis
Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical to the development and functional maintenance of the c...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-08-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00115/full |
| _version_ | 1819092228157472768 |
|---|---|
| author | Noriyuki Koibuchi Winda Ariyani Toshiharu Iwasaki Toshiharu Iwasaki Wataru Miyazaki Erdene Khongorzul Takahito Nakajima Satomi Kameo Hiroshi Koyama Yoshito Tsushima |
| author_facet | Noriyuki Koibuchi Winda Ariyani Toshiharu Iwasaki Toshiharu Iwasaki Wataru Miyazaki Erdene Khongorzul Takahito Nakajima Satomi Kameo Hiroshi Koyama Yoshito Tsushima |
| author_sort | Noriyuki Koibuchi |
| collection | DOAJ |
| description | Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical to the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and thyroid hormone-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. In contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8–10−6 M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 – 10−4 M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10-9 M T4 was augmented by low-dose Gd-DTPA-BMA (10−7 M) but was suppressed by higher dose (10−5 M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10-9 M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10-5 M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker than that of the other compounds. These results indicate that exposure to specific GBCAs may, at least in part, cause toxic effects in the brain by disrupting the action of THs on TRs. The toxic effects of GBCAs may depend on the chemical structure of GBCA and the dose. Thus, it is very important to choose appropriate GBCAs for imaging to prevent adverse side effects. |
| first_indexed | 2024-12-21T22:52:17Z |
| format | Article |
| id | doaj.art-210fa2646dc64a1db09519ce0eeec99d |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T22:52:17Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-210fa2646dc64a1db09519ce0eeec99d2022-12-21T18:47:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922016-08-01710.3389/fendo.2016.00115204371Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesisNoriyuki Koibuchi0Winda Ariyani1Toshiharu Iwasaki2Toshiharu Iwasaki3Wataru Miyazaki4Erdene Khongorzul5Takahito Nakajima6Satomi Kameo7Hiroshi Koyama8Yoshito Tsushima9Department of Integrative Physiology, Gunma University Graduate School of MedicineDepartment of Integrative Physiology, Gunma University Graduate School of MedicineDepartment of Integrative Physiology, Gunma University Graduate School of MedicineDepartment of Liberal Arts and Human Development, Kanagawa University of Human ServiceDepartment of Integrative Physiology, Gunma University Graduate School of MedicineDepartment of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of MedicinDepartment of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of MedicinDepartment of Public Health, Gunma University Graduate School of MedicineDepartment of Public Health, Gunma University Graduate School of MedicineDepartment of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of MedicinGadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical to the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and thyroid hormone-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. In contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8–10−6 M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 – 10−4 M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10-9 M T4 was augmented by low-dose Gd-DTPA-BMA (10−7 M) but was suppressed by higher dose (10−5 M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10-9 M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10-5 M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker than that of the other compounds. These results indicate that exposure to specific GBCAs may, at least in part, cause toxic effects in the brain by disrupting the action of THs on TRs. The toxic effects of GBCAs may depend on the chemical structure of GBCA and the dose. Thus, it is very important to choose appropriate GBCAs for imaging to prevent adverse side effects.http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00115/fullCerebellumdevelopmentendocrine disruptionNeurotoxicologyT3T4 |
| spellingShingle | Noriyuki Koibuchi Winda Ariyani Toshiharu Iwasaki Toshiharu Iwasaki Wataru Miyazaki Erdene Khongorzul Takahito Nakajima Satomi Kameo Hiroshi Koyama Yoshito Tsushima Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis Frontiers in Endocrinology Cerebellum development endocrine disruption Neurotoxicology T3 T4 |
| title | Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis |
| title_full | Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis |
| title_fullStr | Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis |
| title_full_unstemmed | Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis |
| title_short | Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis |
| title_sort | effects of gadolinium based contrast agents on thyroid hormone receptor action and thyroid hormone induced cerebellar purkinje cell morphogenesis |
| topic | Cerebellum development endocrine disruption Neurotoxicology T3 T4 |
| url | http://journal.frontiersin.org/Journal/10.3389/fendo.2016.00115/full |
| work_keys_str_mv | AT noriyukikoibuchi effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT windaariyani effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT toshiharuiwasaki effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT toshiharuiwasaki effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT watarumiyazaki effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT erdenekhongorzul effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT takahitonakajima effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT satomikameo effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT hiroshikoyama effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis AT yoshitotsushima effectsofgadoliniumbasedcontrastagentsonthyroidhormonereceptoractionandthyroidhormoneinducedcerebellarpurkinjecellmorphogenesis |