Enhancement of Dioxin Toxicity with an Anti-Stress Drug, Carbenoxolone, in Mice

Abstract

The effect of the carbenoxolone (CBX) on the subacute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in C57BL/6J mice. The loss of body weight due to TCDD was enhanced by simultaneous treatment with CBX. In agreement with the change in body weight, CBX failed to improve TCDD-induced hepatic hypertrophy and thymic atrophy. Co-treatment of CBX with TCDD tended to cause hepatic hypertrophy more extensively than did TCDD alone, and combined treatment induced significant renal hypertrophy and splenic atrophy which were not seen in mice treated with TCDD or CBX alone. CBX had no effect on the TCDD-mediated induction of hepatic ethoxyresorufin O-deethylase activity, a marker for aryl hydrocarbon receptor (AhR)-linked gene expression. These results suggest that CBX enhances TCDD toxicity by a mechanism(s) distinct from activation of the AhR.