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Article Dans Une Revue Fundamental & Clinical Pharmacology Année : 2022

Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model

Perle Totoson
Célian Peyronnel
  • Fonction : Auteur
Martin Pédard
  • Fonction : Auteur
Marina Cefis
  • Fonction : Auteur
Laurent Bermont
  • Fonction : Auteur
Anne Prigent-Tessier
  • Fonction : Auteur
Clément Prati
  • Fonction : Auteur
Maude Tournier
  • Fonction : Auteur
Daniel Wendling
Christine Marie
  • Fonction : Auteur

Résumé

Abstract This study aimed to explore the effect of Tofacitinib on endothelial dysfunction and cerebral levels of brain‐derived neurotrophic factor (BDNF) in the adjuvant‐induced arthritis (AIA) rat model. Tofacitinib (10 mg/kg twice a day) or vehicle was administered from the first signs of inflammation. Arthritis scores were daily monitored while other parameters including endothelial function assessed from aortic rings, radiographic scores, blood pressure, heart rate, circulating levels of triglycerides, cholesterol, and interleukin (IL)‐1β, tumor necrosis factor‐α (TNF‐α), IL‐17A, and cerebral BDNF levels were determined after 3 weeks of treatment. A group of non‐AIA rats served as controls. In AIA rats, as compared with vehicle, Tofacitinib significantly reduced arthritis and radiographic scores, decreased total cholesterol and low‐density lipoprotein cholesterol (LDL‐C), but changed neither blood pressure nor heart rate and proinflammatory cytokines levels. It also fully restored acetylcholine (Ach)‐induced relaxation ( p < 0.05) through increased nitric oxide (NO) synthase activity, reduced BH 4 deficiency and O 2 −° production, decreased cyclo‐oxygenase‐2 (COX‐2)/arginase activities, and enhanced endothelium‐derived hyperpolarizing factor (EDHF) production. These effects translated into a decrease in atherogenic index and an elevation of BDNF levels in the prefrontal cortex ( p < 0.05) and hippocampus ( p < 0.001). The present study identified Tofacitinib as an efficient therapeutic option to reduce cardiovascular risk and improve BDNF‐dependent cognition in arthritis.
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Dates et versions

hal-04241432 , version 1 (13-10-2023)

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Citer

Perle Totoson, Célian Peyronnel, Aurore Quirié, Martin Pédard, Marina Cefis, et al.. Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model. Fundamental & Clinical Pharmacology, 2022, 36 (2), pp.363-374. ⟨10.1111/fcp.12731⟩. ⟨hal-04241432⟩
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