Histopathological Evaluation of Toxicity of 6-Sulfanilamidoindazole in Lipopolysaccharide (LPS)-Sensitive and -Resistant Mice

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6-Sulfanilamidoindazole (6SAI) is a sulfonamide that induces acute, self-limiting arthritis in rats, and it is reported that endotoxin may modify the sensitivity to 6SAI in rats. In this study, detailed pathological changes were examined in lipopolysaccharide (LPS)- hyporesponsive C3H/HeJ (Lpsd) and LPS-normoresponsive C3H/HeN (Lpsn) mice orally administered with 6SAI (500, 1000 mg/kg) daily for 2 wk. There was no joint swelling observed in any animals treated with 6SAI. Histopathologically, 6SAI-treated mice from both strains showed the same changes such as hypertrophy of hepatocytes, mural thickening of hepatic artery, thickening of adrenal cortex, hypertrophy of thyroid epithelium and hypertrophy of intestinal mucosa. In one animal of the high-dose group of C3H/HeJ strain showed focal epicarditis and capsulitis of thymus and lungs. In the synovium of tarsal joints, there were no changes observed in any 6SAI-treated animals. From this study, it is confirmed that hepatic artery, hepatocytes, thyroid epithelium and intestinal mucosa are target sites of 6SAI in mice. 6SAI-induced toxicity in mice is considered not to be correlated with LPS sensitivity.