Cadmium-induced injury of duodenal epithelial cells in mice and its mechanism / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of cadmium (Cd) exposure in vivo and in vitro on duodenal epithelial cells in mice and the mechanism. METHODS In vivo, C57BL/6 mice were ig administered with CdCI210 mg-kg" once per day for 30 d to establish a chronic cadmium poisoning model, or were ig administered with a single dose of CdCh 80 mg • kg-1 to establish an acute cadmium poisoning model before the survival status and survival rate of mice were observed. Duodenal epithelial cells of acute and chronic cadmium poisoning mice were isolated and cultured. The cells were identified as epithelial cells by E-cadherin immunofluorescence. Then, the content of cadmium ion in duodenal epithelial cells was detected by confocal laser microscopy. In vitro, duodenal epithelial cells of normal C57BL/6 mice were isolated and cultured, and incubated with CdCI2 2.5-100 pmol-L-1 for 24 h. CellTiter-Blue was used to detect cell viability. Subsequently, the duodenal epithelial cells of normal mice were incubated with CdCI215 Mmol • L-1 for 24 h, and cell cycle was detected by flow cytometry. Then, the duodenal epithelial cells of normal C57BL76 mice were incubated with CdCI230 Mmol-L'1 for 3-12 h and the expression of cleaved-caspase 3 was detected by Western blotting. RESULTS Compared with the control group, the activities of mice with chronic cadmium poisoning were all normal. The mice with acute cadmium poisoning showed depression, less food intake and death. At the 5th day of acute cadmium exposure, the survival rate of mice decreased to 40%. The content of cadmium ion in duodenal epithelial cells of acute and chronic cadmium poisoning mice increased significantly (F<0.01). Furthermore, CdCI2 inhibited the viability of duodenal epithelial cells cultured in vitro and the half inhibitory concentration (IC50) was (24.55±0.84) pmol-L-1. Compared with the control group, CdCI2 blocked the cell cycle of duodenal epithelial cells at Go/G, phase (P<0.05), and the expression of cleaved-caspase 3 in duodenal epithelial cells was significantly increased after CdCI2 treatment for 6, 9 and 12 h (P<0.05, P<0.01). CONCLUSION Cadmium that enters the body through the digestive tract can be absorbed by duodenal epithelial cells and cause damage to the cells. The mechanism of cadmium-induced damage may be related to cell cycle arrest and caspase 3-mediated apoptosis.