Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation

Int Immunopharmacol. 2017 Sep;50:243-250. doi: 10.1016/j.intimp.2017.07.004. Epub 2017 Jul 12.


Background and aim: Rheumatoid arthritis treatment aims to control joint damage and any associated complications such as cardiovascular disease. Most anti-inflammatory drugs have a high tendency to cause gastro-intestinal irritation. The present study is designed to investigate the anti-inflammatory effect of carvedilol and to study its effect on gastric mucosa.

Experimental approach: Lornoxicam (1.3mg/kg) or carvedilol (10mg/kg) was administrated orally 1h before histamine injection into animals of a histamine-induced paw edema model and orally daily for 11days into animals of a formaldehyde-induced arthritis model. Tumor necrosis factor-α and prostaglandin E2 were measured in animals of the formaldehyde-induced arthritis model. The effect of lornoxicam and carvedilol on gastric mucosa was assessed in normal rats and after induction of cold stress ulcer.

Results: Carvedilol succeeded in reducing hind paw edema in both histamine-induced paw edema and formaldehyde-induced arthritis and in reducing the elevated level of tumor necrosis factor-α and prostaglandin E2 nearly with near equal efficacy compared with lornoxicam. Carvedilol did not show any ulcerative effect on the gastric mucosa of normal rats, and its use was associated with an improvement of both the gross and histopathological pictures of gastric ulcers in animals of the cold stress ulcer model compared with lornoxicam treated rats.

Conclusion: The current findings support the use of carvedilol both in the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. The use of carvedilol was not associated with any gastro-intestinal tract irritation.

Keywords: Arthritis; Carvedilol; Gastric ulceration; Lornoxicam.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Rheumatoid / drug therapy*
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Dinoprostone / blood
  • Disease Models, Animal
  • Edema / chemically induced
  • Edema / drug therapy*
  • Formaldehyde
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / immunology
  • Gastric Mucosa / pathology
  • Histamine
  • Humans
  • Male
  • Propanolamines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Stomach Ulcer / drug therapy*
  • Tumor Necrosis Factor-alpha / blood


  • Anti-Inflammatory Agents
  • Carbazoles
  • Propanolamines
  • Tumor Necrosis Factor-alpha
  • Carvedilol
  • Formaldehyde
  • Histamine
  • Dinoprostone