Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies
Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding...
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1994
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v49_n1_p43_Coirini http://hdl.handle.net/20.500.12110/paper_09600760_v49_n1_p43_Coirini |
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paper:paper_09600760_v49_n1_p43_Coirini2023-06-08T15:57:23Z Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies antiinflammatory agent corticosterone deflazacort dexamethasone glucocorticoid receptor methylprednisolone ornithine decarboxylase animal experiment animal tissue article brain drug receptor binding hypophysis intravenous drug administration liver nonhuman rat thymus Animal Anti-Inflammatory Agents, Steroidal Binding, Competitive Body Weight Brain Cerebral Cortex Corticosterone Dexamethasone Hippocampus In Vitro Liver Male Methylprednisolone Organ Weight Ornithine Decarboxylase Pituitary Gland, Anterior Prednisone Pregnenediones Rats Rats, Sprague-Dawley Receptors, Glucocorticoid Thymus Gland Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippopocampus and methyl-prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hipopocampus and liver, wheras IC50 the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippopocamus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti-inflammatory steroid during chronic therapeutic regimes. © 1994. 1994 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v49_n1_p43_Coirini http://hdl.handle.net/20.500.12110/paper_09600760_v49_n1_p43_Coirini |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
antiinflammatory agent corticosterone deflazacort dexamethasone glucocorticoid receptor methylprednisolone ornithine decarboxylase animal experiment animal tissue article brain drug receptor binding hypophysis intravenous drug administration liver nonhuman rat thymus Animal Anti-Inflammatory Agents, Steroidal Binding, Competitive Body Weight Brain Cerebral Cortex Corticosterone Dexamethasone Hippocampus In Vitro Liver Male Methylprednisolone Organ Weight Ornithine Decarboxylase Pituitary Gland, Anterior Prednisone Pregnenediones Rats Rats, Sprague-Dawley Receptors, Glucocorticoid Thymus Gland |
| spellingShingle |
antiinflammatory agent corticosterone deflazacort dexamethasone glucocorticoid receptor methylprednisolone ornithine decarboxylase animal experiment animal tissue article brain drug receptor binding hypophysis intravenous drug administration liver nonhuman rat thymus Animal Anti-Inflammatory Agents, Steroidal Binding, Competitive Body Weight Brain Cerebral Cortex Corticosterone Dexamethasone Hippocampus In Vitro Liver Male Methylprednisolone Organ Weight Ornithine Decarboxylase Pituitary Gland, Anterior Prednisone Pregnenediones Rats Rats, Sprague-Dawley Receptors, Glucocorticoid Thymus Gland Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| topic_facet |
antiinflammatory agent corticosterone deflazacort dexamethasone glucocorticoid receptor methylprednisolone ornithine decarboxylase animal experiment animal tissue article brain drug receptor binding hypophysis intravenous drug administration liver nonhuman rat thymus Animal Anti-Inflammatory Agents, Steroidal Binding, Competitive Body Weight Brain Cerebral Cortex Corticosterone Dexamethasone Hippocampus In Vitro Liver Male Methylprednisolone Organ Weight Ornithine Decarboxylase Pituitary Gland, Anterior Prednisone Pregnenediones Rats Rats, Sprague-Dawley Receptors, Glucocorticoid Thymus Gland |
| description |
Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippopocampus and methyl-prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hipopocampus and liver, wheras IC50 the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippopocamus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti-inflammatory steroid during chronic therapeutic regimes. © 1994. |
| title |
Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| title_short |
Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| title_full |
Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| title_fullStr |
Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| title_full_unstemmed |
Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies |
| title_sort |
binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. in vivo and in vitro studies |
| publishDate |
1994 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v49_n1_p43_Coirini http://hdl.handle.net/20.500.12110/paper_09600760_v49_n1_p43_Coirini |
| _version_ |
1768546217519742976 |