Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: modulation of oxidative stress and inflammatory mediators.
Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10mg/kg/day p.o. for 21days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α & IL-6), and eicosanoids (PGE2 & LTB4) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids.
Biochemistry Division, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif, Saudi Arabia. hany_h_arab@yahoo.com
Hany H
HH
Arab
Maha M
MM
El-Sawalhi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002465:Cell Movement / Q000187:drug effects; D015232:Dinoprostone / Q000097:blood; D004487:Edema / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002227:Carbazoles; D018836:Inflammation Mediators; D011412:Propanolamines; D000077261:Carvedilol; D007975:Leukotriene B4; D015232:Dinoprostone