In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis

Hafiz Muhammad Irfan; Awais Anjum; Mulazim Hussain Asim; Saeed Ur Rasheed; Alamgeer; Farzana Siddique

doi:10.1007/s10787-024-01553-5

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis

Inflammopharmacology. 2024 Aug 27. doi: 10.1007/s10787-024-01553-5. Online ahead of print.

Authors

Hafiz Muhammad Irfan¹, Awais Anjum², Mulazim Hussain Asim², Saeed Ur Rasheed², Alamgeer³, Farzana Siddique⁴

Affiliations

¹ College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan. muhammad.irfan@uos.edu.pk.
² College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan.
³ Punjab University College of Pharmacy, University of the Punjab, Lahore, 54000, Pakistan.
⁴ Institute of Science and Nutrition, University of Sargodha, Sargodha, 40100, Pakistan.

PMID: 39192161
DOI: 10.1007/s10787-024-01553-5

Abstract

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

Keywords: Animal model; CFA; ELISA; Fluoxetine; INF-γ; RT-PCR.