Tehran University of Medical Sciences Acta Medica Iranica 0044-6025 56 5 2018 05 20 287 294 EN Farnaz Malekmarzban Department of Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. Mohammad Seyedabadi Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran. Mohammad Hossein Ghahremani Department of Toxicology and Pharmacology, School of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran. Shima Aliebrahimi Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. Peiman Habibollahi Department of Toxicology and Pharmacology, School of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran. Shohreh Tavajohi Department of Toxicology and Pharmacology, School of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran. Seyed Nasser Ostad Department of Toxicology and Pharmacology, School of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2017 01 03 2017 05 17 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. https://acta.tums.ac.ir/index.php/acta/article/view/6118 https://acta.tums.ac.ir/index.php/acta/article/download/6118/5086