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Open AccessArticle

The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species

1
Unit of Endocrinology, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis 15, 00135 Rome, Italy
2
Unit of Biochemistry, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis 15, 00135 Rome, Italy
3
Unit of Biology and Genetics, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Piazza Lauro de Bosis 15, 00135 Rome, Italy
4
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
5
Division of Rheumatic and Musculoskeletal Diseases, Leeds Institute of Molecular Medicine, University of Leeds, Woodhouse, Leeds LS2 9JT, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Antioxidants 2020, 9(9), 786; https://doi.org/10.3390/antiox9090786
Received: 5 August 2020 / Revised: 20 August 2020 / Accepted: 22 August 2020 / Published: 25 August 2020
(This article belongs to the Special Issue Redox-Active Molecules as Therapeutic Agents)
Systemic sclerosis (SSc) is a multi-system connective tissue disease characterized by the increased deposition of extracellular matrix proteins such as collagen and fibronectin. Although the pathogenesis is not completely understood, a number of studies suggest that free radicals could be the major contributors to the disease. Indeed, different studies demonstrated how oxidative stress could contribute to the fibrotic process activation at the level of the skin and visceral organs. Emerging evidences highlight the beneficial effects of sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), which protects different cell lines from the cell damage induced by reactive oxygen species (ROS). These data make sildenafil a good candidate for therapeutic treatment aimed to protect biological macromolecules against oxidative damage, thus preserving cell viability. The purpose of this study was to evaluate the sensitivity of SSc dermal fibroblasts to an oxidative insult and the ability for sildenafil to prevent/reduce the DNA damage due to ROS action. Additionally, we evaluated the capacity for sildenafil to influence redox homeostasis and cytotoxicity, as well as cell proliferation and cell cycle progression. We demonstrated that SSc fibroblasts have an increased sensitivity to a pro-oxidant environment in comparison to healthy controls. The sildenafil treatment reduced ROS-induced DNA damage, counteracted the negative effects of ROS on cell viability and proliferation, and promoted the activity of specific enzymes involved in redox homeostasis maintenance. To our knowledge, in this report, we demonstrate, for the first time, that sildenafil administration prevents ROS-induced instability in human dermal fibroblasts isolated by SSc patients. These results expand the use of PDE5i as therapeutic agents in SSc by indicating a protective role in tissue damage induced by oxidative insult. View Full-Text
Keywords: oxidative stress; sildenafil; DNA damage; systemic sclerosis oxidative stress; sildenafil; DNA damage; systemic sclerosis
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MDPI and ACS Style

Di Luigi, L.; Duranti, G.; Antonioni, A.; Sgrò, P.; Ceci, R.; Crescioli, C.; Sabatini, S.; Lenzi, A.; Caporossi, D.; Del Galdo, F.; Dimauro, I.; Antinozzi, C. The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species. Antioxidants 2020, 9, 786.

AMA Style

Di Luigi L, Duranti G, Antonioni A, Sgrò P, Ceci R, Crescioli C, Sabatini S, Lenzi A, Caporossi D, Del Galdo F, Dimauro I, Antinozzi C. The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species. Antioxidants. 2020; 9(9):786.

Chicago/Turabian Style

Di Luigi, Luigi; Duranti, Guglielmo; Antonioni, Ambra; Sgrò, Paolo; Ceci, Roberta; Crescioli, Clara; Sabatini, Stefania; Lenzi, Andrea; Caporossi, Daniela; Del Galdo, Francesco; Dimauro, Ivan; Antinozzi, Cristina. 2020. "The Phosphodiesterase Type 5 Inhibitor Sildenafil Improves DNA Stability and Redox Homeostasis in Systemic Sclerosis Fibroblasts Exposed to Reactive Oxygen Species" Antioxidants 9, no. 9: 786.

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