The anti-inflammatory and apoptotic effects of atorvastatin in combination with celecoxib in adjuvant-induced arthritis in rats

Abstract

Rowaida Refaat, Mona Salama, Maher A Kamel and Sherihan Salah EL Din

Statins seem to have anti-inflammatory effects independent of their lipid-lowering abilities. Previous studies demonstrated a strong synergy between statins and non-steroidal anti-inflammatory drugs in growth inhibition and apoptosis induction in cultured cancer cells. This study aimed at evaluating the combined anti-inflammatorty and apoptotic effects of atorvastatin and celecoxib in adjuvant-induced arthritis in rats. Adjuvant arthritis was induced in Sprague-Dawley rats by intradermal injection of 0.1 ml suspension of heat-killed Mycobacterium butyricum (12 mg/ml) in incomplete Freund’s adjuvant. Rats were treated orally with atorvastatin (10 mg/kg/day), celecoxib (3 mg/kg/day) and their combination from day 12 to day 27 post-adjuvant injection. Arthritis progression was assessed by hind paw swelling and arthrogram scores. Serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) were measured. Caspase-3 activity and DNA fragmentation were determined in tibiotarsal joints tissue to evaluate apoptosis. Celecoxib proved to be more effective, than atorvastatin in suppressing clinical severity of arthritis, reducing serum levels of VEGF, CRP and TNF-α and increasing serum levels of IL-10. Caspase-3 activity and DNA fragmentation were more significantly enhanced by atorvastatin. Combining atorvastatin and celecoxib provided higher efficacy, in reducing inflammation and inducing apoptosis, than either agent alone.

Share this article