title: Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells.
abstract: Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.
authors.affiliation: Department of Movement, Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Rome, Italy.
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Duranti
authors.affiliation: Department of Movement, Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Rome, Italy. roberta.ceci@uniroma4.it.|Department of Movement, Human and Health Sciences, Università degli Studi di Roma "Foro Italico", Piazza Lauro de Bosis, 6, I-00135, Rome, Italy. roberta.ceci@uniroma4.it.
authors.forename: Roberta
authors.identifier: 0000-0002-8900-8839
authors.initials: R
authors.lastname: Ceci
authors.affiliation: Department of Movement, Human and Health Sciences, Unit of Endocrinology, Università degli Studi di Roma "Foro Italico", Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sgrò
authors.affiliation: Department of Movement, Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Sabatini
authors.affiliation: Department of Movement, Human and Health Sciences, Unit of Endocrinology, Università degli Studi di Roma "Foro Italico", Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Luigi
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000068581:Tadalafil / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D058986:Phosphodiesterase 5 Inhibitors; D017382:Reactive Oxygen Species; D000068581:Tadalafil; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: C2C12 skeletal muscle cells; Oxidative metabolism; PDE5Is; Redox status; Tadalafil