Deflazacort induced stronger immunosuppression than expected |
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Authors: | Rocio E Gonzalez-Castañeda Estela Adriana Castellanos-Alvarado Maria Rosa Flores-Marquez Oscar Gonzalez-Perez Sonia Luquin Joaquin Garcia-Estrada Cesar Ramos-Remus |
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Institution: | (1) Neuroscience Division, Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico;(2) Department of Pathology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico;(3) Department of Neurosciences, Centro Universitario en Ciencias de la Salud de la Universidad de Guadalajara, Guadalajara, México;(4) Department of Rheumatology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Mexico;(5) Present address: Colomos 2292, Providencia, Guadalajara, Jalisco 44620, Mexico |
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Abstract: | Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic
glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic
administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats
were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally,
and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions
due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed
rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation
of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that
the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed
infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11
times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased
in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells
in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent
licensed dose produced a stronger immunosuppressive effect—systemic and in brain tissue—than PDN, but induced less neuronal
damage. The immunesuppressant magnitude of DFZ should be further studied in clinical settings. |
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Keywords: | Deflazacort Immunosuppression Prednisone |
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