SYSTEMIC HISTOPATHOLOGY OF RATS TREATED WITH 6-SULFANILAMIDOINDAZOLE,A NOVEL ARTHRITOGENIC SULFONAMIDE

6-Sulfanilamidoindazole (6SAI) is a sulfonamide that induces acute, se lf-limiting arthritis in rats, and 6SAI-induced arthritis is thought t o be a model for testing anti-inflammatory agents. In this study, in o rder to clarify the location of arthritis and relationships between ar thritis and other changes in this model, we have investigated the deta iled pathologic changes in rats administered orally with 6SAI (125, 25 0, 500 mg/kg) daily for 4 wk in a time-course experiment. Moderate to severe arthritis was observed in rats of middle- and high-dose groups. Histologically, in the affected ankle, exudative synovitis and periar thritis were observed at 1 wk, granulation tissue formation with angio genesis and periosteal new bone formation at 2 wk, and marked fibrosis of affected area at 4 wk, respectively. In addition to these changes, in periarticular and periosteal tissues of affected ankles, subendoth elial insudation of small-sized arteries and medial fibrinoid degenera tion of medium-sized arteries were observed at 1 and 2 wk and intimal thickening and medial hypertrophy at 4 wk, respectively. No arterial c hanges were observed in the unaffected ankles. Similar arterial change s were often observed in the liver, thyroid glands, and lungs and rare ly in various organs and tissues. Acute inflammation of serous tissues such as mesentery, mediastinum, and capsule of spleen or thymus were also present in 6SAI-treated groups, and it was sometimes accompanied by arteritis. In addition, in 6SAI-treated rats, follicular hyperplasi a of thyroid glands and pituitary changes, which are thought to be rel ated to depression of thyroid hormone production by 6SAI, were observe d. These results show that 6SAI induces not only arthritis but also ar teritis, serositis, and thyroid change, and it is necessary to take th e interaction between these changes into consideration when anti-infla mmatory agents are tested in this model.