The aim of the present paper was to investigate the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to collagen-induced arthritis. Lewis rats developed an erosive hind paw arthritis when immunized with an emulsion of bovine type II collagen (CII) and incomplete Freund's adjuvant. Macroscopic clinical evidence of type II collagen-induced arthritis (CIA) first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 35 in the C11challenged rats; and CIA severity progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathology of CIA included an hyperplastic synovium that invaded and eroded articular cartilage at the joint margins, and subchondral bone resorption associated with bone-derived, multinucleated cell-containing granulomatous lesions in the rat hind paw. Treatment of rats with tempol (10 mg/kg daily i.p.) starting at the onset of arthritis (day 25), delayed the development of the clinical signs at days 26-35 and improved histological status in the knee and paw. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in inflamed joints from collagen-treated rats. Joints tissue sections from collagen -treated rats also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen -treated rats which had received tempol. Furthermore, radiographic evidence of protection from bone resorption, osteophyte formation and soft tissue swelling was apparent in the tibiotarsai joints of tempol-treated rat. This study provides the first evidence that tempol, a small molecule which permeates biological membranes and scavenges ROS, attenuates the degree of chronic inflammation and tissue damage associated with collagen-induced arthritis in the rat.
Effects of tempol, a membrane-permeable radical scavenger, in a rodent model of collagen-induced arthritis
Britti D;
1999-01-01
Abstract
The aim of the present paper was to investigate the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to collagen-induced arthritis. Lewis rats developed an erosive hind paw arthritis when immunized with an emulsion of bovine type II collagen (CII) and incomplete Freund's adjuvant. Macroscopic clinical evidence of type II collagen-induced arthritis (CIA) first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 35 in the C11challenged rats; and CIA severity progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathology of CIA included an hyperplastic synovium that invaded and eroded articular cartilage at the joint margins, and subchondral bone resorption associated with bone-derived, multinucleated cell-containing granulomatous lesions in the rat hind paw. Treatment of rats with tempol (10 mg/kg daily i.p.) starting at the onset of arthritis (day 25), delayed the development of the clinical signs at days 26-35 and improved histological status in the knee and paw. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in inflamed joints from collagen-treated rats. Joints tissue sections from collagen -treated rats also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen -treated rats which had received tempol. Furthermore, radiographic evidence of protection from bone resorption, osteophyte formation and soft tissue swelling was apparent in the tibiotarsai joints of tempol-treated rat. This study provides the first evidence that tempol, a small molecule which permeates biological membranes and scavenges ROS, attenuates the degree of chronic inflammation and tissue damage associated with collagen-induced arthritis in the rat.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
