Modulatory Effects of Reducing Agents on Aryl Hydrocarbon Receptor Activity in Mice

Background and Objective: The aryl hydrocarbon receptor (AhR) is a Fundamental environmental sensor and essential transcription factor that in vitro and in vivo modes andstudy on patients show AhR plays inevitable roles in cellular processes as detoxification of xenobiotics and cell proliferation, apoptosis that are important in malignancies. AhR also affects on invasion and migration of cells that is important in metastasis of tumors. AhR is also important for the physiological conditions of some vital organs as liver, gonads, immune system and cardiovascular systems. Dysfunction in AhR can cause disorder in this vital organ which can lead to a kind of disease or death. Recently, AhR seems to be sensitive to oxidative alteration. However, there is little information about the effects of stress, especially oxidative stress, on the aryl hydrocarbon receptor signaling. Therefore, in this study, we investigated the effects of oxidizing compounds on aryl hydrocarbon receptors performance in mice. Materials and Methods: Male BALB/c albino mice liver were exposed to the suggested endogenous ligand of AhR, 6-formylindolo [3, 2-b] carbazole (FICZ) alone or in combination with cadmium (Cd), mercury (Hg) and buthionine-(S, R)-sulfoximine (BSO). Findings :For the first time, a clear association between CYP1A1 transcription and changes in the cellular oxidative state was shown. In vivo findings demonstrated that the time course of AhR activation/inhibition is characterized by an increase/decrease in the GSH/GSSG ratio. Conclusion: Based on these findings, we propose that many environmental pollutants and oxidants by an alteration in the intracellular oxidative potential may interfere with the normal function of AhR target genes and caused any disorder in many physiological cell processes and dysfunction in some vital organ as liver and gonad and causes some important diseases as cancer or immune system disease.

کلیدواژه های Modulatory Effects of Reducing Agents on Aryl Hydrocarbon Receptor Activity in Mice:

Aryl hydrocarbon receptors ، reducting agent ، FICZ ، NAC ، GSH / GSSG ratio