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Drug-Repurposing Strategy for Dimethyl Fumarate.
Giunta, Salvatore; D'Amico, Agata Grazia; Maugeri, Grazia; Bucolo, Claudio; Romano, Giovanni Luca; Rossi, Settimio; Eandi, Chiara M; Pricoco, Elisabetta; D'Agata, Velia.
Afiliação
  • Giunta S; Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • D'Amico AG; Department of Drug and Health Sciences, University of Catania, 95123 Catania, Italy.
  • Maugeri G; Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Bucolo C; Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Romano GL; Center for Research in Ocular Pharmacology (CERFO), University of Catania, 95123 Catania, Italy.
  • Rossi S; Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • Eandi CM; Center for Research in Ocular Pharmacology (CERFO), University of Catania, 95123 Catania, Italy.
  • Pricoco E; Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", 80131 Napoli, Italy.
  • D'Agata V; Department of Ophthalmology, University of Lausanne, Fondation Asile des Aveugles, Jules Gonin Eye Hospital, 1004 Lausanne, Switzerland.
Pharmaceuticals (Basel) ; 16(7)2023 Jul 07.
Article em En | MEDLINE | ID: mdl-37513886
ABSTRACT
In the area of drug discovery, repurposing strategies represent an approach to discover new uses of approved drugs besides their original indications. We used this approach to investigate the effects of dimethyl fumarate (DMF), a drug approved for relapsing-remitting multiple sclerosis and psoriasis treatment, on early injury associated with diabetic retinopathy (DR). We used an in vivo streptozotocin (STZ)-induced diabetic rat model. Diabetes was induced by a single injection of STZ in rats, and after 1 week, a group of animals was treated with a daily intraperitoneal injection of DMF or a vehicle. Three weeks after diabetes induction, the retinal expression levels of key enzymes involved in DR were evaluated. In particular, the biomarkers COX-2, iNOS, and HO-1 were assessed via Western blot and immunohistochemistry analysis. Diabetic rats showed a significant retinal upregulation of COX-2 and iNOS compared to the retina of normal rats (non-diabetic), and an increase in HO-1 was also observed in the STZ group. This latter result was due to a mechanism of protection elicited by the pathological condition. DMF treatment significantly induced the retinal expression of HO-1 in STZ-induced diabetic animals with a reduction in iNOS and COX-2 retinal levels. Taken together, these results suggested that DMF might be useful to counteract the inflammatory process and the oxidative response in DR. In conclusion, we believe that DMF represents a potential candidate to treat diabetic retinopathy and warrants further in vivo and clinical evaluation.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article