Figure 2.
Phospho-non-steroidal anti-inflammatory drugs (NSAIDs) prevent the development of rat adjuvant arthritis. (A–C) Phospho-aspirin prevents the development of rat adjuvant arthritis. Arthritis was induced in rats by injecting Freund's adjuvant (FA) into their tail. Rats were treated daily by oral gavage for 18 days with phospho-aspirin (P-A; 110 mg·kg−1) or aspirin (ASA; 35 mg·kg−1; equimolar doses) suspended in corn oil. (A) The hind paw weight (left) and inflammation (clinical) score (right) of the various study groups. Data are expressed as mean ± standard deviation; n= 5 rats per group. *Significantly different compared with FA/vehicle-treated group; P < 0.03. (B) Histological evaluation of hind paw joints. Formalin-fixed decalcified tissue from affected joints was stained with haematoxylin and eosin and examined under an Olympus BX41 microscope (20×; Olympus, Center Valley, PA, USA) and photographed with an Olympus DP25 digital camera. FA induced oedema and infiltration with inflammatory cells, endothelial cell proliferation and synovial thickening, obliterating the free joint space (compare with normal). phospho-aspirin greatly reduced the inflammatory infiltrate and tissue oedema, restoring the free joint space. aspirin had a similar but less pronounced effect. (C) Bone resorption and inflammation were scored. Values are mean ± SEM. *significantly different compared with FA/vehicle-treated group; *P < 0.03; **P < 0.07. (D, E) Phospho-ibuprofen and phospho-sulindac prevented the development of rat adjuvant arthritis. Arthritis was induced by injecting Freund's adjuvant (FA) into the tail of the rat. Rats were treated with phospho-ibuprofen (P-I; 300 mg·kg−1) or phospho-sulindac (P-S; 150 mg·kg−1), suspended in corn oil, given daily by oral gavage for 18 days. D: Representative photographs of resected hind paws (left panel) and tails (right panel) from the various experimental groups are shown. Red arrow: area of necrosis. E: Hind paw weight (left panel) and (clinical) inflammation score (right panel) of phospho-sulindac and phospho-ibuprofen-treated rats. Values are mean ± standard deviation. *Significantly different compared with FA-treated group; P < 0.01.