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

• Main Authors: Farnaz Malekmarzban, Mohammad Seyedabad, Mohammad Hossein Ghahreman, Shima Aliebrahimi, Peiman Habibollahi, Shohreh Tavajohi, Seyed Nasser Ostad
• Format: Article
• Language: English
• Published: Tehran University of Medical Sciences 2018-05-01
• Series: Acta Medica Iranica
• Subjects: Heavy metal; Detoxification; Free radical; iNOS; Colon carcinoma
• Online Access: https://acta.tums.ac.ir/index.php/acta/article/view/6118

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.