Granisetron and carvedilol can protect experimental rats againstadjuvant-induced arthritis

Abstract

Context: Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications.

Objective: We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT₃ receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats.

Materials and methods: Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving granisetron (2.5 mg/kg/day) and carvedilol (10 mg/kg/day). Serum-specific rheumatoid, immunological, inflammatory and oxidative stress biomarkers were assessed. A confirmatory histopathological study on joints and spleens was performed.

Results: Granisetron administration significantly improved all the measured biomarkers, with the values of rheumatoid factor, matrix metalloproteinase-3, cartilage oligomeric matrix protein, immunoglobulin G, antinuclear antibody and myeloperoxidase being restored back to normal levels. Carvedilol administration significantly improved all biomarkers, with serum MPO value restored back to normal levels.

Discussion and conclusions: Serotonin 5-HT₃ receptor blockers and adrenergic receptor blockers, represented by granisetron and carvedilol, may represent new promising protective strategies against RA, at least owing to immune-modulator, anti-inflammatory and antioxidant potentials.

Keywords: Rheumatoid arthritis; carvedilol; complete Freund's adjuvant; dexamethasone; granisetron; methotrexate.