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

  • Farnaz Malekmarzban Department of Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
  • Mohammad Seyedabad Department of Pharmacology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
  • Mohammad Hossein Ghahreman 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 Mail Department of Toxicology and Pharmacology, School of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Heavy metal, Detoxification, Free radical, iNOS, Colon carcinoma


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.


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How to Cite
Malekmarzban F, Seyedabad M, Ghahreman MH, Aliebrahimi S, Habibollahi P, Tavajohi S, Ostad SN. Role of Nitric Oxide and Metallothionein in Cytotoxic Activity of Cadmium in Caco-2 Cells. Acta Med Iran. 56(5):287-294.
Original Article(s)