Camellia sinensis tea melanin suppresses transformation of the aryl hydrocarbon receptor and prevents against dioxin-induced toxicity in mice

Abstract

The suppressive effects of Camellia sinensis tea melanin (CSTM) on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were disclosed for the first time. CSTM strongly inhibited TCDD-induced toxicity with IC50 equalling 20.4 mu g mL(-1). Daily administration of CSTM (40 mg kg(-1), p.o.) prevented TCDD-induced body weight loss, ameliorated TCDD-induced mortality and prevented TCDD-induced hepatomegaly and thymic atrophy. Co-administration of CSTM significantly inhibited TCDD-induced hepatic CYP1 A1 activity. CSTM retarded transformation of AhR in vitro. In animals treated with CSTM, the antibody-secreting cells produced significantly (P < 0.05) more antibodies (32-34%) than the antigen control. Administration of TCDD caused a suppression of antibody-forming cells of 29-33% against the antigen control level. Co-administration of CSTM restored immunity to the control level. We demonstrated that CSTM directly competed with TCDD during the transformation of AhR and suppressed the downstream activation of genes associated with TCDD toxicity.