Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression
The pathogenesis of priapism in sickle cell disease (SCD) is closely linked to oxidative stress and reduced bioavailability of nitric oxide (NO) in penile tissue. Resveratrol, a potent natural antioxidant, has demonstrated protective effects in various vascular disorders. To evaluate the therapeutic...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1551533/full |
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| author | Carolina Oliveira Splendore Tammyris Helena Rebecchi Silveira Dalila Andrade Pereira Beatriz Pereira Bossarino Mariana Gonçalves de Oliveira Fabiano Beraldi Calmasini Arthur L. Burnett Fernando Ferreira Costa Fábio Henrique Silva |
| author_facet | Carolina Oliveira Splendore Tammyris Helena Rebecchi Silveira Dalila Andrade Pereira Beatriz Pereira Bossarino Mariana Gonçalves de Oliveira Fabiano Beraldi Calmasini Arthur L. Burnett Fernando Ferreira Costa Fábio Henrique Silva |
| author_sort | Carolina Oliveira Splendore |
| collection | DOAJ |
| description | The pathogenesis of priapism in sickle cell disease (SCD) is closely linked to oxidative stress and reduced bioavailability of nitric oxide (NO) in penile tissue. Resveratrol, a potent natural antioxidant, has demonstrated protective effects in various vascular disorders. To evaluate the therapeutic effects of resveratrol on priapism, oxidative stress markers, and NO-cGMP signaling in the penile tissue of transgenic SCD mice. Male wild-type (C57BL/6) and transgenic SCD mice were treated with resveratrol (100 mg/kg/day, gavage) or vehicle for 2 weeks. Functional studies were conducted on CC strips mounted in organ baths to assess relaxation responses to acetylcholine (ACh), sodium nitroprusside (SNP), and nitrergic stimulation (electrical field stimulation, EFS). The oxidative stress markers (NOX-2, 4-HNE, and 3-NT), cGMP levels, and the mRNA expression of endothelial nitric oxide synthase (eNOS) and phosphodiesterase type 5 (PDE5) were evaluated. Resveratrol treatment decreased exaggerated ACh-, SNP-, and EFS-induced relaxation responses in SCD mice. It also reduced oxidative stress markers (NOX-2, 4-HNE, and 3-NT) and normalized eNOS and PDE5 mRNA expression in the CC of SCD mice. Additionally, cGMP levels in the CC were significantly increased by resveratrol treatment. These effects were specific to SCD mice and not observed in wild-type mice. In conclusion, resveratrol reduces oxidative stress and restores NO-cGMP signaling in the penile tissue, reducing the exaggerated cavernosal relaxation characteristic of priapism in SCD. These findings highlight resveratrol as a promising therapeutic candidate for managing priapism in patients with SCD. |
| format | Article |
| id | doaj-art-8b5b0a838cbf4863bec4735e6ec92cde |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-8b5b0a838cbf4863bec4735e6ec92cde2025-08-20T03:19:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15515331551533Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expressionCarolina Oliveira Splendore0Tammyris Helena Rebecchi Silveira1Dalila Andrade Pereira2Beatriz Pereira Bossarino3Mariana Gonçalves de Oliveira4Fabiano Beraldi Calmasini5Arthur L. Burnett6Fernando Ferreira Costa7Fábio Henrique Silva8Laboratory of Pharmacology, São Francisco University Medical School, São Paulo, BrazilLaboratory of Pharmacology, São Francisco University Medical School, São Paulo, BrazilLaboratory of Pharmacology, São Francisco University Medical School, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista de Medicina, Department of Pharmacology, São Paulo, BrazilLaboratory of Pharmacology, São Francisco University Medical School, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista de Medicina, Department of Pharmacology, São Paulo, BrazilThe James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine, Baltimore, MD, United StatesHematology and Hemotherapy Center, University of Campinas, São Paulo, BrazilLaboratory of Pharmacology, São Francisco University Medical School, São Paulo, BrazilThe pathogenesis of priapism in sickle cell disease (SCD) is closely linked to oxidative stress and reduced bioavailability of nitric oxide (NO) in penile tissue. Resveratrol, a potent natural antioxidant, has demonstrated protective effects in various vascular disorders. To evaluate the therapeutic effects of resveratrol on priapism, oxidative stress markers, and NO-cGMP signaling in the penile tissue of transgenic SCD mice. Male wild-type (C57BL/6) and transgenic SCD mice were treated with resveratrol (100 mg/kg/day, gavage) or vehicle for 2 weeks. Functional studies were conducted on CC strips mounted in organ baths to assess relaxation responses to acetylcholine (ACh), sodium nitroprusside (SNP), and nitrergic stimulation (electrical field stimulation, EFS). The oxidative stress markers (NOX-2, 4-HNE, and 3-NT), cGMP levels, and the mRNA expression of endothelial nitric oxide synthase (eNOS) and phosphodiesterase type 5 (PDE5) were evaluated. Resveratrol treatment decreased exaggerated ACh-, SNP-, and EFS-induced relaxation responses in SCD mice. It also reduced oxidative stress markers (NOX-2, 4-HNE, and 3-NT) and normalized eNOS and PDE5 mRNA expression in the CC of SCD mice. Additionally, cGMP levels in the CC were significantly increased by resveratrol treatment. These effects were specific to SCD mice and not observed in wild-type mice. In conclusion, resveratrol reduces oxidative stress and restores NO-cGMP signaling in the penile tissue, reducing the exaggerated cavernosal relaxation characteristic of priapism in SCD. These findings highlight resveratrol as a promising therapeutic candidate for managing priapism in patients with SCD.https://www.frontiersin.org/articles/10.3389/fphar.2025.1551533/full3-nitrotyrosinecGMPhemoglobinreactive oxygen speciescorpus cavernosum |
| spellingShingle | Carolina Oliveira Splendore Tammyris Helena Rebecchi Silveira Dalila Andrade Pereira Beatriz Pereira Bossarino Mariana Gonçalves de Oliveira Fabiano Beraldi Calmasini Arthur L. Burnett Fernando Ferreira Costa Fábio Henrique Silva Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression Frontiers in Pharmacology 3-nitrotyrosine cGMP hemoglobin reactive oxygen species corpus cavernosum |
| title | Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression |
| title_full | Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression |
| title_fullStr | Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression |
| title_full_unstemmed | Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression |
| title_short | Resveratrol attenuates the priapism phenotype in sickle cell mice by restoring NO-cGMP-PDE5 signaling and reducing NADPH oxidase 2 expression |
| title_sort | resveratrol attenuates the priapism phenotype in sickle cell mice by restoring no cgmp pde5 signaling and reducing nadph oxidase 2 expression |
| topic | 3-nitrotyrosine cGMP hemoglobin reactive oxygen species corpus cavernosum |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1551533/full |
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