Role of Nitric Oxide and Metallothionein in Cytotoxic Activity of Cadmium in Caco-2 Cells
-
Farnaz Malekmarzban
,
Mohammad Seyedabadi
,
Mohammad Hossein Ghahremani
,
Shima Aliebrahimi
,
Peiman Habibollahi
,
Shohreh Tavajohi
,
Seyed Nasser Ostad
Abstract
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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| Files | ||
| Issue | Vol 56, No 5 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Heavy metal Detoxification Free radical iNOS Colon carcinoma | ||
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