Abstract
Prazosin, a selective alpha(1) adrenergic receptor antagonist, with documented anti-inflammatory potential, was evaluated for its antiarthritic efficacy by targeting specifically TNF-alpha. The antiarthritic attribute of prazosin validated through in vitro screening comprised thermally provoked denaturation of bovine serum albumin (BSA) and egg albumin along with membrane stabilization evaluation at a concentration of 100-6400 mu g/mL, while in vivo screening comprised formaldehyde-instigated arthritis at the doses of 5, 10, and 20 mg/kg and complete Freund's adjuvant (CFA)-induced arthritis at 20 mg/kg dose. Paw swelling, body weight, arthritic score, hematological parameters, and histological and radiographic examination of ankle joints were assessed for a period of 28 days after CFA immunization. Moreover, the proinflammatory cytokine TNF-alpha level was also assessed through quantitative real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Prazosin revealed significant antiarthritic effect evident through protein denaturation inhibition in the egg albumin and the BSA model, stabilization of red blood cell membrane in the membrane stabilizing assay, and reduction in paw volume in formaldehyde-induced arthritis. Likewise, prazosin exhibited propitious antiarthritic effects in the CFA-provoked arthritis model manifested by paw volume and arthritic score alleviation, substantial weight loss prevention, and preservation of the normal hematological and biochemical profile. Histological and X-ray investigation unveiled no substantive structural alterations in treated rat's ankle joints. The TNF-alpha expression level was also reduced. Thus, the current study is suggestive that prazosin exhibits a strong antiarthritic potential possibly through inhibition of TNF-alpha.