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Article ; Online: Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats.

Marín-Prida, Javier / Liberato, José Luiz / Llópiz-Arzuaga, Alexey / Stringhetta-Padovani, Karina / Pavón-Fuentes, Nancy / Leopoldino, Andréia Machado / Cruz, Osmany Guirola / González, Ignacio Hernández / Pérez, Mariela León / Camins, Antoni / Ferreira Dos Santos, Wagner / Uyemura, Sergio Akira / Pardo-Andreu, Gilberto L / Pentón-Rol, Giselle

Current pharmaceutical design

2022 Volume 28, Issue 14, Page(s) 1187–1197

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 ...

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-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-β) 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.
MeSH term(s)	Animals ; Brain Ischemia/drug therapy ; Brain Ischemia/metabolism ; Disease Models, Animal ; Molecular Docking Simulation ; NADPH Oxidases/metabolism ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Phycocyanin/pharmacology ; Phycocyanin/therapeutic use ; Rats ; Reperfusion Injury/drug therapy
Chemical Substances	Neuroprotective Agents ; Phycocyanin (11016-15-2) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2022-05-15
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612828666220506145542
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Article ; Online: Immunogenicity profile in African green monkeys of a vaccine candidate based on a mutated form of human Interleukin-15.

Rodríguez-Álvarez, Yunier / Batista-Roche, Lino Gerardo / Llopiz-Arzuaga, Alexey / Puente-Pérez, Pedro / Martínez-Castillo, Rafael / Castro-Velazco, Jorge / Santos-Savio, Alicia

BMC immunology

2021 Volume 22, Issue 1, Page(s) 79

Abstract: Background: Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based ... ...

Abstract	Background: Interleukin (IL)-15 is a proinflammatory T-cell growth factor overexpressed in several autoimmune diseases such as rheumatoid arthritis. Our initial strategy to neutralize the increased levels of IL-15 consisted in a vaccine candidate based on the recombinant modified human IL-15 (mhIL-15) mixed with the alum adjuvant. A previous study in non-human primates Macaca fascicularis has shown that vaccination induces neutralizing antibodies against native IL-15, without affecting animal behavior, clinical status, or the percentage of IL-15-dependent cell populations. However, the mhIL-15 used as an antigen was active in the IL-2-dependent cytotoxic T-cell line CTLL-2, which could hinder its therapeutic application. The current article evaluated the immunogenicity in African green monkeys of a vaccine candidate based on IL-15 mutant D8SQ108S, an inactive form of human IL-15. Results: IL-15 D8SQ108S was inactive in the CTLL-2 bioassay but was able to competitively inhibit the biological activity of human IL-15. Immunization with 200 µg of IL-15 mutant combined with alum elicited anti-IL-15 IgG antibodies after the second and third immunizations. The median values of anti-IL-15 antibody titers were slightly higher than those generated in animals immunized with 200 µg of mhIL-15. The highest antibody titers were induced after the third immunization in monkeys vaccinated with 350 µg of IL-15 D8SQ108S. In addition, sera from immunized animals inhibited the biological activity of human IL-15 in CTLL-2 cells. The maximum neutralizing effect was observed after the third immunization in sera of monkeys vaccinated with the highest dose of the IL-15 mutant. These sera also inhibited the proliferative activity of simian IL-15 in the CTLL-2 bioassay and did not affect the IL-2-induced proliferation of the aforementioned T-cell line. Finally, it was observed that vaccination neither affects the animal behavior nor the general clinical parameters of immunized monkeys. Conclusion: Immunization with inactive IL-15 D8SQ108S mixed with alum generated neutralizing antibodies specific for human IL-15 in African green monkeys. Based on this fact, the current vaccine candidate could be more effective than the one based on biologically active mhIL-15 for treating autoimmune disorders involving an uncontrolled overproduction of IL-15.
MeSH term(s)	Alum Compounds ; Animals ; Antibodies, Neutralizing/metabolism ; Cell Proliferation ; Chlorocebus aethiops ; Cytotoxicity, Immunologic ; Humans ; Immunization ; Immunogenicity, Vaccine ; Interleukin-15/genetics ; Interleukin-15/immunology ; Mice ; Mutation/genetics ; T-Lymphocytes/immunology ; Vaccines/immunology
Chemical Substances	Alum Compounds ; Antibodies, Neutralizing ; Interleukin-15 ; Vaccines ; aluminum sulfate (34S289N54E)
Language	English
Publishing date	2021-12-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041500-X
ISSN	1471-2172 ; 1471-2172
ISSN (online)	1471-2172
ISSN	1471-2172
DOI	10.1186/s12865-021-00470-4
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Article ; Online: The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.

Marín-Prida, Javier / Rodríguez-Ulloa, Arielis / Besada, Vladimir / Llopiz-Arzuaga, Alexey / Batista, Nathália Vieira / Hernández-González, Ignacio / Pavón-Fuentes, Nancy / Marciano Vieira, Érica Leandro / Falcón-Cama, Viviana / Acosta, Emilio F / Martínez-Donato, Gillian / Cervantes-Llanos, Majel / Lingfeng, Dai / González, Luis J / Fernández-Massó, Julio Raúl / Guillén-Nieto, Gerardo / Pentón-Arias, Eduardo / Amaral, Flávio Almeida / Teixeira, Mauro Martins /

Pentón-Rol, Giselle

Frontiers in immunology

2023 Volume 14, Page(s) 1227268

Abstract: Introduction: The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of ... ...

Abstract	Introduction: The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis. Methods: Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization. Results and discussion: C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology. Conclusions: These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.
MeSH term(s)	Humans ; Mice ; Animals ; Phycocyanin/adverse effects ; Nociception ; Proteome ; Neutrophil Infiltration ; Mice, Inbred C57BL ; Neuroblastoma ; Arthritis, Experimental ; Arthritis, Rheumatoid/drug therapy ; Inflammation/drug therapy ; Gene Expression ; Cytokines/pharmacology ; Pain
Chemical Substances	phycocyanobilin (36NUT04V2K) ; Phycocyanin (11016-15-2) ; Proteome ; Cytokines
Language	English
Publishing date	2023-10-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1227268
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Article ; Online: Phycocyanobilin reduces brain injury after endothelin-1- induced focal cerebral ischaemia.

Pavón-Fuentes, Nancy / Marín-Prida, Javier / Llópiz-Arzuaga, Alexey / Falcón-Cama, Viviana / Campos-Mojena, Rosario / Cervantes-Llanos, Majel / Piniella-Matamoros, Beatriz / Pentón-Arias, Eduardo / Pentón-Rol, Giselle

Clinical and experimental pharmacology & physiology

2019 Volume 47, Issue 3, Page(s) 383–392

Abstract: Pharmacological therapies for interrupting biochemical events of the ischaemic cascade and protecting against stroke in humans are as yet unavailable. Up to now, the neuroprotective activity in cerebral ischaemia of phycocyanobilin (PCB), a tetrapyrrolic ...

Abstract	Pharmacological therapies for interrupting biochemical events of the ischaemic cascade and protecting against stroke in humans are as yet unavailable. Up to now, the neuroprotective activity in cerebral ischaemia of phycocyanobilin (PCB), a tetrapyrrolic natural antioxidant, has not been fully examined. Here, we evaluated if PCB protects PC12 neuronal cells against oxygen and glucose deprivation plus reperfusion, and its protective effects in a rat model of endothelin-1-induced focal brain ischaemia. PCB was purified from the cyanobacteria Spirulina platensis and characterized by spectrophotometric, liquid and gas chromatography and mass spectrometry techniques. In Wistar rats, PCB at 50, 100 and 200 μg/kg or phosphate-buffered saline (vehicle) was administered intraperitoneally at equal subdoses in a therapeutic schedule (30 minutes, 1, 3 and 6 hours after the surgery). Brain expression of myelin basic protein (MBP) and the enzyme CNPase was determined by immunoelectron microscopy. PCB was obtained with high purity (>95%) and the absence of solvent contaminants and was able to ameliorate PC12 cell ischaemic injury. PCB treatment significantly decreased brain infarct volume, limited the exploratory behaviour impairment and preserved viable cortical neurons in ischaemic rats in a dose-dependent manner, compared to the vehicle group. Furthermore, PCB at high doses restored the MBP and CNPase expression levels in ischaemic rats. An improved PCB purification method from its natural source is reported, obtaining PCB that is suitable for pharmacological trials showing neuroprotective effects against experimental ischaemic stroke. Therefore, PCB could be a therapeutic pharmacological alternative for ischaemic stroke patients.
MeSH term(s)	Animals ; Brain Injuries/chemically induced ; Brain Injuries/drug therapy ; Brain Injuries/pathology ; Brain Ischemia/chemically induced ; Brain Ischemia/drug therapy ; Brain Ischemia/pathology ; Endothelin-1/toxicity ; Male ; PC12 Cells ; Phycobilins/therapeutic use ; Phycocyanin/therapeutic use ; Rats ; Rats, Wistar
Chemical Substances	Endothelin-1 ; Phycobilins ; Phycocyanin (11016-15-2) ; phycocyanobilin (36NUT04V2K)
Language	English
Publishing date	2019-12-06
Publishing country	Australia
Document type	Journal Article
ZDB-ID	189277-0
ISSN	1440-1681 ; 0305-1870 ; 0143-9294
ISSN (online)	1440-1681
ISSN	0305-1870 ; 0143-9294
DOI	10.1111/1440-1681.13214
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Zs.A 990: Show issues

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Article ; Online: Obtention and characterization of the recombinant simian Interleukin-15 in Escherichia coli for the preclinical assessment of an IL-15-based therapeutic vaccine.

Rodríguez-Álvarez, Yunier / Martínez-Cordovez, Klaudia / Llopiz-Arzuaga, Alexey / Ramos-Gómez, Yassel / Besada-Pérez, Vladimir / García-Lines, Dayana / Santos-Savio, Alicia

Preparative biochemistry & biotechnology

2017 Volume 47, Issue 9, Page(s) 889–900

Abstract: Recombinant simian IL-15 (siIL-15) was obtained for the preclinical assessment of an anti-human IL-15 vaccine. For this purpose, the cDNA from peripheral blood mononuclear cells of a Macaca fascicularis monkey was cloned into a pIL-2 vector. The siIL-15 ... ...

Abstract	Recombinant simian IL-15 (siIL-15) was obtained for the preclinical assessment of an anti-human IL-15 vaccine. For this purpose, the cDNA from peripheral blood mononuclear cells of a Macaca fascicularis monkey was cloned into a pIL-2 vector. The siIL-15 was expressed in Escherichia coli strain W3110 as an insoluble protein which accounted for 13% of the total cellular proteins. Inclusion bodies were solubilized in an 8 M urea solution, which was purified by ion exchange and reverse phase chromatography up to 92% purity. The protein identity was validated by electrospray ionization-mass spectrometry, confirming the presence of the amino acids which distinguish the siIL-15 from human IL-15. The purified siIL-15 stimulates the proliferation of cytotoxic T-lymphocytes line (CTLL)-2 and Kit 225 cells with EC
Language	English
Publishing date	2017-10-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1322522-4
ISSN	1532-2297 ; 1082-6068
ISSN (online)	1532-2297
ISSN	1082-6068
DOI	10.1080/10826068.2017.1365238
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Article ; Online: Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice.

Pentón-Rol, Giselle / Lagumersindez-Denis, Nielsen / Muzio, Luca / Bergami, Alessandra / Furlan, Roberto / Fernández-Massó, Julio R / Nazabal-Galvez, Marcelo / Llópiz-Arzuaga, Alexey / Herrera-Rolo, Tania / Veliz-Rodriguez, Tania / Polentarutti, Nadia / Marín-Prida, Javier / Raíces-Cruz, Ivette / Valenzuela-Silva, Carmen / Teixeira, Mauro Martins / Pentón-Arias, Eduardo

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2016 Volume 11, Issue 1, Page(s) 153–167

Abstract: Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina ... ...

Abstract	Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.p.) or IFN-beta (2000 IU, s.c.) was administered daily once a day or every other day, respectively, starting at disease onset, which differ among EAE mice between 11 and 15 days postinduction. Histological and immunohistochemistry (anti-Mac-3, anti-CD3 and anti-APP) assessments were performed in spinal cord in the postinduction time. Global gene expression in the brain was analyzed with the Illumina Mouse WG-6_V2 BeadChip microarray and the expression of particular genes, assessed by qPCR using the Fast SYBR Green RT-PCR Master Mix. Oxidative stress parameters (malondialdehyde, peroxidation potential, CAT/SOD ratio and GSH) were determined spectrophoto-metrically. Results showed that C-Pc ameliorates the clinical deterioration of animals, an effect that expresses the reduction of the inflammatory infiltrates invading the spinal cord tissue, the axonal preservation and the down-regulation of IL-17 expression in brain tissue and serum. C-Pc and IFN-beta improved the redox status in mice subjected to EAE, while microarray analysis showed that both treatments shared a common subset of differentially expressed genes, although they also differentially modulated another subset of genes. Specifically, C-Pc mainly modulated the expression of genes related to remyelination, gliogenesis and axon-glia processes. Taken together, our results indicate that C-Pc has significant therapeutic effects against EAE, mediated by the dynamic regulation of multiple biological processes.
MeSH term(s)	Animals ; Anti-Inflammatory Agents/pharmacology ; Brain/drug effects ; Brain/pathology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Gene Expression/drug effects ; Immunohistochemistry ; Interferon-beta/pharmacology ; Mice ; Mice, Inbred C57BL ; Nerve Regeneration/drug effects ; Neuroprotective Agents/pharmacology ; Oligonucleotide Array Sequence Analysis ; Oxidative Stress/drug effects ; Phycocyanin/pharmacology ; Real-Time Polymerase Chain Reaction ; Spinal Cord/drug effects ; Spinal Cord/pathology
Chemical Substances	Anti-Inflammatory Agents ; Neuroprotective Agents ; Phycocyanin (11016-15-2) ; Interferon-beta (77238-31-4)
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-015-9642-9
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Article: Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

Marín-Prida, Javier / Pavón-Fuentes, Nancy / Llópiz-Arzuaga, Alexey / Fernández-Massó, Julio R / Delgado-Roche, Liván / Mendoza-Marí, Yssel / Santana, Seydi Pedroso / Cruz-Ramírez, Alieski / Valenzuela-Silva, Carmen / Nazábal-Gálvez, Marcelo / Cintado-Benítez, Alberto / Pardo-Andreu, Gilberto L / Polentarutti, Nadia / Riva, Federica / Pentón-Arias, Eduardo / Pentón-Rol, Giselle

Toxicology and applied pharmacology. 2013 Oct. 1, v. 272, no. 1

2013

Abstract: Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of ... ...

Abstract	Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H₂O₂ and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.
Keywords	brain ; carotid arteries ; cell viability ; gene expression ; gene expression regulation ; genes ; glutamic acid ; hydrogen peroxide ; inflammation ; oxidative stress ; rats ; reverse transcriptase polymerase chain reaction ; stroke ; superoxide dismutase
Language	English
Dates of publication	2013-1001
Size	p. 49-60.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2013.05.021
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: C-Phycocyanin is neuroprotective against global cerebral ischemia/reperfusion injury in gerbils.

Pentón-Rol, Giselle / Marín-Prida, Javier / Pardo-Andreu, Gilberto / Martínez-Sánchez, Gregorio / Acosta-Medina, Emilio Felino / Valdivia-Acosta, Alain / Lagumersindez-Denis, Nielsen / Rodríguez-Jiménez, Efraín / Llópiz-Arzuaga, Alexey / López-Saura, Pedro Antonio / Guillén-Nieto, Gerardo / Pentón-Arias, Eduardo

Brain research bulletin

2011 Volume 86, Issue 1-2, Page(s) 42–52

Abstract: Although the huge economic and social impact and the predicted incidence increase, neuroprotection for ischemic stroke remains as a therapeutically empty niche. In the present study, we investigated the rationale of the C-Phycocyanin (C-PC) treatment on ... ...

Abstract	Although the huge economic and social impact and the predicted incidence increase, neuroprotection for ischemic stroke remains as a therapeutically empty niche. In the present study, we investigated the rationale of the C-Phycocyanin (C-PC) treatment on global cerebral ischemia/reperfusion (I/R) injury in gerbils. We demonstrated that C-PC given either prophylactically or therapeutically was able to significantly reduce the infarct volume as assessed by triphenyltetrazolium chloride (TTC) staining and the neurological deficit score 24h post-stroke. In addition, C-PC exhibited a protective effect against hippocampus neuronal cell death, and significantly improved the functional outcome (locomotor behavior) and gerbil survival after 7 days of reperfusion. Malondialdehyde (MDA), peroxidation potential (PP) and ferric reducing ability of plasma (FRAP) were assayed in serum and brain homogenates to evaluate the redox status 24h post-stroke. The treatment with C-PC prevented the lipid peroxidation and the increase of FRAP in both tissue compartments. These results suggest that the protective effects of C-PC are most likely due to its antioxidant activity, although its anti-inflammatory and immuno-modulatory properties reported elsewhere could also contribute to neuroprotection. To our knowledge, this is the first report of the neuroprotective effect of C-PC in an experimental model of global cerebral I/R damage, and strongly indicates that C-PC may represent a potential preventive and acute disease modifying pharmacological agent for stroke therapy.
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; Brain Ischemia/mortality ; Brain Ischemia/pathology ; Brain Ischemia/physiopathology ; Gerbillinae ; Hippocampus/cytology ; Hippocampus/drug effects ; Hippocampus/pathology ; Humans ; Lipid Peroxidation/drug effects ; Male ; Malondialdehyde/metabolism ; Motor Activity/drug effects ; Motor Activity/physiology ; Neurons/drug effects ; Neurons/pathology ; Neuroprotective Agents/pharmacology ; Oxidation-Reduction ; Oxidative Stress ; Phycocyanin/pharmacology ; Random Allocation ; Reperfusion Injury/pathology ; Reperfusion Injury/prevention & control ; Survival Rate
Chemical Substances	Neuroprotective Agents ; Phycocyanin (11016-15-2) ; Malondialdehyde (4Y8F71G49Q)
Language	English
Publishing date	2011-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2011.05.016
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Zs.A 1243: Show issues

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Article ; Online: Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats.

Toxicology and applied pharmacology

2013 Volume 272, Issue 1, Page(s) 49–60

Abstract	Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Brain Chemistry/drug effects ; Brain Chemistry/genetics ; Cell Survival/drug effects ; Cerebrovascular Disorders/drug therapy ; Cerebrovascular Disorders/physiopathology ; Coloring Agents ; Cytokines/biosynthesis ; Genes, MHC Class II/drug effects ; Glutamic Acid/metabolism ; Hydrogen Peroxide/pharmacology ; Inflammation/genetics ; Male ; Microarray Analysis ; Oxidation-Reduction ; Oxidative Stress/drug effects ; PC12 Cells ; Phycobilins/isolation & purification ; Phycobilins/pharmacology ; Phycocyanin/isolation & purification ; Phycocyanin/pharmacology ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction ; Spirulina/chemistry ; Tetrazolium Salts ; Thiazoles ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Biomarkers ; Coloring Agents ; Cytokines ; Phycobilins ; Tetrazolium Salts ; Thiazoles ; Vascular Endothelial Growth Factor A ; Phycocyanin (11016-15-2) ; phycocyanobilin (36NUT04V2K) ; Glutamic Acid (3KX376GY7L) ; Hydrogen Peroxide (BBX060AN9V) ; thiazolyl blue (EUY85H477I)
Language	English
Publishing date	2013-10-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2013.05.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: C-Phycocyanin protects SH-SY5Y cells from oxidative injury, rat retina from transient ischemia and rat brain mitochondria from Ca2+/phosphate-induced impairment.

Marín-Prida, Javier / Pentón-Rol, Giselle / Rodrigues, Fernando Postalli / Alberici, Luciane Carla / Stringhetta, Karina / Leopoldino, Andréia Machado / Naal, Zeki / Polizello, Ana Cristina Morseli / Llópiz-Arzuaga, Alexey / Rosa, Marcela Nunes / Liberato, José Luiz / Santos, Wagner Ferreira Dos / Uyemura, Sergio Akira / Pentón-Arias, Eduardo / Curti, Carlos / Pardo-Andreu, Gilberto L

Brain research bulletin

2012 Volume 89, Issue 5-6, Page(s) 159–167

Abstract: Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, ... ...

Abstract	Oxidative stress and mitochondrial impairment are essential in the ischemic stroke cascade and eventually lead to tissue injury. C-Phycocyanin (C-PC) has previously been shown to have strong antioxidant and neuroprotective actions. In the present study, we assessed the effects of C-PC on oxidative injury induced by tert-butylhydroperoxide (t-BOOH) in SH-SY5Y neuronal cells, on transient ischemia in rat retinas, and in the calcium/phosphate-induced impairment of isolated rat brain mitochondria (RBM). In SH-SY5Y cells, t-BOOH induced a significant reduction of cell viability as assessed by an MTT assay, and the reduction was effectively prevented by treatment with C-PC in the low micromolar concentration range. Transient ischemia in rat retinas was induced by increasing the intraocular pressure to 120mmHg for 45min, which was followed by 15min of reperfusion. This event resulted in a cell density reduction to lower than 50% in the inner nuclear layer (INL), which was significantly prevented by the intraocular pre-treatment with C-PC for 15min. In the RBM exposed to 3mM phosphate and/or 100μM Ca(2+), C-PC prevented in the low micromolar concentration range, the mitochondrial permeability transition as assessed by mitochondrial swelling, the membrane potential dissipation, the increase of reactive oxygen species levels and the release of the pro-apoptotic cytochrome c. In addition, C-PC displayed a strong inhibitory effect against an electrochemically-generated Fenton reaction. Therefore, C-PC is a potential neuroprotective agent against ischemic stroke, resulting in reduced neuronal oxidative injury and the protection of mitochondria from impairment.
MeSH term(s)	Animals ; Brain/drug effects ; Brain/metabolism ; Calcium Phosphates/toxicity ; Cell Line, Tumor ; Humans ; Ischemia/chemically induced ; Ischemia/metabolism ; Ischemia/prevention & control ; Male ; Mitochondria/drug effects ; Mitochondria/metabolism ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Phycocyanin/pharmacology ; Phycocyanin/therapeutic use ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Retina/drug effects ; Retina/metabolism ; Retinal Vessels/drug effects ; Retinal Vessels/metabolism ; tert-Butylhydroperoxide/toxicity
Chemical Substances	Calcium Phosphates ; Reactive Oxygen Species ; Phycocyanin (11016-15-2) ; tert-Butylhydroperoxide (955VYL842B) ; calcium phosphate (97Z1WI3NDX)
Language	English
Publishing date	2012-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2012.08.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

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