Pedro Nobre Azevedo

Scopus Publications

Fluoxetine Reshapes Macrophage Membrane Sphingolipids and Inflammatory Response Without Affecting Extracellular Vesicle Biogenesis upon Inactivated SARS-CoV-2 Stimulation
Jonatan C. S. de Carvalho, Pedro Nobre-Azevedo, Pedro V. da Silva-Neto, Bianca T. M. Oliveira, Lucas A. Tavares, Diana M. Toro, Andrews O. Borges, Murillo A. Nascimento, Eurico Arruda, Ronaldo B. Martins, Fausto Almeida, Carlos A. Sorgi
Membranes, 2026
Sphingolipids (SL) are essential structural and bioactive components of cell membranes, remarkably involved in inflammatory signaling and membrane dynamics. Dysregulation of SL metabolism contributes to pathological inflammation and cellular stress. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FXT), are known inhibitors of acid sphingomyelinase (aSMase), although their impact on macrophage SL remodeling and inflammatory responses remains unclear. Here, we investigated the modulation of FXT on SL species composition and inflammatory activation in THP-1-derived macrophages stimulated with inactivated SARS-CoV-2 particles, which is a model of viral-induced inflammation. Sphingolipidomic profiling revealed that FXT pre-treatment markedly reduced ceramide (Cer) species while increasing sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels, consistent with inhibition of the aSMase-Cer axis. These changes were accompanied by attenuation of proinflammatory components, including interleucin (IL)-6, IL-1β, and matrix metalloproteinase (MMP)-9, indicating that SL remodeling correlates with reduced macrophage activation. Despite pronounced alterations in membrane lipid composition, the quantification of extracellular vesicles (EVs) released by FXT-treated macrophages remained unchanged, however the EVs size distribution was smaller compared to non-treated cells. Altogether, our findings demonstrate that FXT reshapes SL metabolism and lipid membrane composition, thereby diminishing macrophage activation without affecting EVs biogenesis. This study emphasizes the immunometabolic role of SL on membrane reprogramming as a mechanism by which pharmacological aSMase inhibition modulates viral inflammation responses.
Enhanced lipidomics workflows for plasma and extracellular vesicles through advanced liquid chromatography-tandem mass spectrometry integrated
Adriana F.L. Vilela, Miguel R. Patrício, Pedro Nobre-Azevedo, Jonatan C.S. de Carvalho, Thiago V. Defelippo-Felippe, Nathan N.H. Pontes, Daniel L. Rodrigues, Bianca T.M. Oliveira, Pedro V. da Silva-Neto, Viviani Nardini, Ana P.M. Fernandes, Fausto Almeida, Lucia H. Faccioli, Carlos A. Sorgi
Talanta, 2025
High-resolution targeted mass spectrometry for comprehensive quantification of sphingolipids: clinical applications and characterization of extracellular vesicles
Thiago V.D. Felippe, Diana M. Toro, Jonatan C.S. de Carvalho, Pedro Nobre-Azevedo, Luiz F.M. Rodrigues, Bianca T.M. Oliveira, Pedro V. da Silva-Neto, Adriana F.L. Vilela, Fausto Almeida, Lúcia H. Faccioli, Carlos A. Sorgi
Analytical Biochemistry, 2025
Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19
Diana Mota Toro, Pedro V. da Silva-Neto, Jonatan C. S. de Carvalho, Carlos A. Fuzo, Malena M. Pérez, Vinícius E. Pimentel, Thais F. C. Fraga-Silva, Camilla N. S. Oliveira, Glaucia R. Caruso, Adriana F. L. Vilela, Pedro Nobre-Azevedo, Thiago V. Defelippo-Felippe, Jamille G. M. Argolo, Augusto M. Degiovani, Fátima M. Ostini, Marley R. Feitosa, Rogerio S. Parra, Fernando C. Vilar, Gilberto G. Gaspar, José J. R. da Rocha, Omar Feres, Gabriel P. Costa, Sandra R. C. Maruyama, Elisa M. S. Russo, Ana Paula M. Fernandes, Isabel K. F. M. Santos, Adriana Malheiro, Ruxana T. Sadikot, Vânia L. D. Bonato, Cristina R. B. Cardoso, Marcelo Dias-Baruffi, Átila A. Trapé, Lúcia H. Faccioli, Carlos A. Sorgi, and
Cells, 2023
SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a “lipid storm”, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

RECENT SCHOLAR PUBLICATIONS

Fluoxetine Reshapes Macrophage Membrane Sphingolipids and Inflammatory Response Without Affecting Extracellular Vesicle Biogenesis upon Inactivated SARS-CoV-2 Stimulation
JCS de Carvalho, P Nobre-Azevedo, PV da Silva-Neto, BTM Oliveira, ...
Membranes 16 (3), 98 , 2026
2026.0
Citations: 1
EXTRATOS DAS FOLHAS E CASCAS DE RHIZOPHORA MANGLE: ATIVIDADE ANTIOXIDANTE E IMUNOMODULADORA EM MACRÓFAGOS NUM CENÁRIO DE PROFILAXIA ANTI-INFLAMATÓRIA
MA Nascimento, A Borges, P Azevedo, LFM Rodrigues, C Sorgi, ...
Anais do Congresso Brasileiro de Iniciação Científica, 33-39 , 2025
2025.0
Enhanced lipidomics workflows for plasma and extracellular vesicles through advanced liquid chromatography-tandem mass spectrometry integrated
AFL Vilela, MR Patrício, P Nobre-Azevedo, JCS de Carvalho, ...
Talanta 291, 127847 , 2025
2025.0
Citations: 3
High-resolution targeted mass spectrometry for comprehensive quantification of sphingolipids: clinical applications and characterization of extracellular vesicles
TVD Felippe, DM Toro, JCS de Carvalho, P Nobre-Azevedo, ...
Analytical Biochemistry 698, 115732 , 2025
2025.0
Citations: 8
Correlation of matrix metalloproteinases and inflammation parameters in postmenopausal women
KNB Gato, PN Azevedo, AP Silva, C Moraes, ÁA Trapé, J Fiamoncini, ...
Abstracts , 2025
2025.0
Optimizing Lipidomics Analysis Workflows for Biological Fluids and Extracellular Vesicles with Integrated Liquid Chromatography Tandem Mass Spectrometry Approaches
AFL Vilela, MR Patrício, TV Defelippo-Felippe, V Nardini, NNH Pontes, ...
bioRxiv, 2024.11. 08.622653 , 2024
2024.0
Citations: 1
High-resolution targeted mass spectrometry for comprehensive quantification of sphingolipids: clinical applications and characterization of extracellular vesicles
TVD Felippe, DM Toro, J de Carvalho, P Nobre-Azevedo, LFM Rodrigues, ...
Analytical Biochemistry 698, 12 , 2024
2024.0
Plasma sphingomyelin disturbances: unveiling its dual role as a crucial Immunopathological factor and a severity prognostic biomarker in COVID-19
DM Toro, PV da Silva-Neto, JCS de Carvalho, CA Fuzo, MM Perez, ...
Cells 12 (15), 1938 , 2023
2023.0
Citations: 11
Produção de etanol de segunda geração a partir da celulose contida no coco verde
MA Nascimento, P Azevedo, L Menezes, L Duarte, T Correa, S Ramos
Revista Processando o Saber 15, 16-31 , 2023
2023.0
High-Resolution Targeted Mass Spectrometry for Quantification of Sphingolipids: Clinical Applications and Characterization of Extracellular Vesicles
DM Toro, TV Defelippo-Felippe, J Carvalho, P Nobre-Azevedo, ...
Available at SSRN 4992085 , 0

MOST CITED SCHOLAR PUBLICATIONS

Plasma sphingomyelin disturbances: unveiling its dual role as a crucial Immunopathological factor and a severity prognostic biomarker in COVID-19
DM Toro, PV da Silva-Neto, JCS de Carvalho, CA Fuzo, MM Perez, ...
Cells 12 (15), 1938 , 2023
2023.0
Citations: 11
High-resolution targeted mass spectrometry for comprehensive quantification of sphingolipids: clinical applications and characterization of extracellular vesicles
TVD Felippe, DM Toro, JCS de Carvalho, P Nobre-Azevedo, ...
Analytical Biochemistry 698, 115732 , 2025
2025.0
Citations: 8
Enhanced lipidomics workflows for plasma and extracellular vesicles through advanced liquid chromatography-tandem mass spectrometry integrated
AFL Vilela, MR Patrício, P Nobre-Azevedo, JCS de Carvalho, ...
Talanta 291, 127847 , 2025
2025.0
Citations: 3
Fluoxetine Reshapes Macrophage Membrane Sphingolipids and Inflammatory Response Without Affecting Extracellular Vesicle Biogenesis upon Inactivated SARS-CoV-2 Stimulation
JCS de Carvalho, P Nobre-Azevedo, PV da Silva-Neto, BTM Oliveira, ...
Membranes 16 (3), 98 , 2026
2026.0
Citations: 1
Optimizing Lipidomics Analysis Workflows for Biological Fluids and Extracellular Vesicles with Integrated Liquid Chromatography Tandem Mass Spectrometry Approaches
AFL Vilela, MR Patrício, TV Defelippo-Felippe, V Nardini, NNH Pontes, ...
bioRxiv, 2024.11. 08.622653 , 2024
2024.0
Citations: 1
EXTRATOS DAS FOLHAS E CASCAS DE RHIZOPHORA MANGLE: ATIVIDADE ANTIOXIDANTE E IMUNOMODULADORA EM MACRÓFAGOS NUM CENÁRIO DE PROFILAXIA ANTI-INFLAMATÓRIA
MA Nascimento, A Borges, P Azevedo, LFM Rodrigues, C Sorgi, ...
Anais do Congresso Brasileiro de Iniciação Científica, 33-39 , 2025
2025.0
Correlation of matrix metalloproteinases and inflammation parameters in postmenopausal women
KNB Gato, PN Azevedo, AP Silva, C Moraes, ÁA Trapé, J Fiamoncini, ...
Abstracts , 2025
2025.0
High-resolution targeted mass spectrometry for comprehensive quantification of sphingolipids: clinical applications and characterization of extracellular vesicles
TVD Felippe, DM Toro, J de Carvalho, P Nobre-Azevedo, LFM Rodrigues, ...
Analytical Biochemistry 698, 12 , 2024
2024.0
Produção de etanol de segunda geração a partir da celulose contida no coco verde
MA Nascimento, P Azevedo, L Menezes, L Duarte, T Correa, S Ramos
Revista Processando o Saber 15, 16-31 , 2023
2023.0
High-Resolution Targeted Mass Spectrometry for Quantification of Sphingolipids: Clinical Applications and Characterization of Extracellular Vesicles
DM Toro, TV Defelippo-Felippe, J Carvalho, P Nobre-Azevedo, ...
Available at SSRN 4992085 , 0