Role of Nitric Oxide and Metallothionein in Cytotoxic Activity of Cadmium in Caco-2 Cells

Cadmium (Cd) induces carcinogenicity and cytotoxicity through a variety of mechanisms. Metallothioneins (MTs) play critical roles in metal detoxification and radical scavenging. Here we evaluated the possible involvement of NO and MT in Cd-induced toxicity and resistance development. By utilizing Cd-resistant Caco-2 cells as a model of chronic exposure to Cadmium, we observed that Cd decreased Caco-2 cell proliferation, whereas Cd-resistant cells showed a lower sensitivity to Cd cytotoxicity. L-NAME as an iNOS inhibitor and cPTIO as an NO scavenger induced a significant reduction in Cd-mediated toxicity of parent Caco-2 in spite of resistant cells. In resistant cells, iNOS mRNA expression was declined; however, MT protein synthesis was increased following acute and chronic Cd exposure. It seems that NO synthesis involves in Cd-induced cytotoxicity, while elevated MT expression is associated with Cd detoxification and resistance.