Cardiotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure through lactation in mice.

Abstract

Dioxins are a group of structurally related chemicals that persist in the environment. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener, is a suspected risk factor for cardiac diseases in humans. TCDD induces signs of cardiotoxicity in various animals. Mouse models of TCDD exposure suggest cardiotoxicity phenotypes develop differently depending on the timing and time-course of exposure. In order to clarify and characterize the TCDD-induced cardiotoxicity in the developing period, we utilized mouse pups exposed to TCDD. One day after delivery, groups of nursing C57BL/6J dams were orally administered TCDD at a dose of 0 (Control), 20 (TCDD-20), or 80 μg/kg (TCDD-80) body weight (BW). On postnatal days (PNDs) 7 and 21, pups hearts were examined by histological and gene expression analyses. The TCDD-80 group was found to have a left ventricular remodeling on PND 7, and to develop heart hypertrophy on PND 21. It was accompanied by fibrosis and increased expression of associated genes, such as those for atrial natriuretic peptide (ANP), β-myosin heavy chain (β-MHC), and endothelin-1 (ET-1). These results revealed that TCDD directly induces cardiotoxicity in the postnatal period represented by progressive hypertrophy in which ANP, β-MHC, and ET-1 have potentials to mediate the cardiac hypertrophy and heart failure.