| Full text | |
| Author(s): Show less - |
Marin-Prida, Javier
;
Liberato, Jose Luiz
;
Llopiz-Arzuaga, Alexey
;
Stringhetta-Padovani, Karina
;
Pavon-Fuentes, Nancy
;
Machado Leopoldino, Andreia
;
Guirola Cruz, Osmany
;
Hernandez Gonzalez, Ignacio
;
Leon Perez, Mariela
;
Camins, Antoni
;
dos Santos, Wagner Ferreira
;
Akira Uyemura, Sergio
;
Pardo-Andreu, Gilberto L.
;
Penton-Rol, Giselle
Total Authors: 14
|
| Document type: | Journal article |
| Source: | CURRENT PHARMACEUTICAL DESIGN; v. 28, n. 14, p. 11-pg., 2022-01-01. |
| Abstract | |
Background: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options. Objective: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis. Methods: Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis of NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed. Results: C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurological deficit in a dose-dependent manner, and improved the exploratory activity of I/R rats. This biliprotein inhibited NOX2 expression, a crucial NADPH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-gamma, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-beta) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats. Conclusion: These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia. (AU) | |
| FAPESP's process: | 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer |
| Grantee: | Carlos Curti |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/00374-8 - Analysis of hnRNPK protein in cell lines NB4 and NB4-R2 of acute myeloid leukemia with emphasis in pathogenesis and cell differentiation by all-trans retinoic acid |
| Grantee: | Karina Stringhetta Padovani |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |