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Drug-Repurposing Strategy for Dimethyl Fumarate

Articolo
Data di Pubblicazione:
2023
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.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
diabetic retinopathy; dimethyl fumarate; heme oxygenase-1; retina; streptozotocin
Elenco autori:
Giunta, Salvatore; D'Amico, Agata Grazia; Maugeri, Grazia; Bucolo, Claudio; Romano, Giovanni Luca; Rossi, Settimio; Eandi, Chiara M; Pricoco, Elisabetta; D'Agata, Velia
Autori di Ateneo:
EANDI Chiara Maria
Link alla scheda completa:
https://iris.unito.it/handle/2318/1951052
Link al Full Text:
https://iris.unito.it/retrieve/handle/2318/1951052/1226952/Drug-Repurposing%20Strategy%20for%20Dimethyl%20Fumarate_Pharmaceuticals-16-00974_2023.pdf
Pubblicato in:
PHARMACEUTICALS
Journal
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