Several polyphenols have been shown to activate the aryl hydrocarbon receptor (AHR) in spite of the fact that they bind to the receptor with low affinity. The aim of this study was to investigate whether quercetin (QUE), resveratrol (RES), and curcumin (CUR) interfere with the metabolic degradation of the suggested endogenous AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ) and thereby indirectly activate the AHR. Using recombinant human enzyme, we confirmed earlier reported inhibitory effects of the polyphenols on cytochrome P4501A1 (CYP1A1) activity, and inhibition of metabolic clearance of FICZ was documented in FICZ-treated immortalized human keratinocytes (HaCaT). CYP1A1 activity was induced in HaCaT cells by all three compounds, and when they were added together with FICZ, a prolonged activation was observed after a dose-dependent inhibition period. The same pattern of responses was seen at the transcriptional level as determined with a CYP1A1 reporter assay in human liver hepatoma (HepG2) cells. To test the ability of the polyphenols to activate the AHR in the absence of FICZ, the cells were treated in medium, which in contrast to commercial batches of medium did not contain background levels of FICZ. Importantly, AHR activation was only observed in the commercial medium. Taken together, these findings suggest that QUE, RES, and CUR induce CYP1A1 in an indirect manner by inhibiting the metabolic turnover of FICZ. Humans are exposed to these compounds through the diet and nutritional supplements, and we propose that altered systemic levels of FICZ caused by such compounds may have physiological consequences.

There has been a great deal of attention and research devoted on nanoparticels (NPs) over the last 10 years. From current knowledge in the field of nanotoxicology, it has become evident that the most NPs, if not all are more toxic than bulk materials. The rapid progress and developing has been leading to concerns about the potential risk associated with the use and application of NPs on human health and the environment. Silver nanoparticles (SNPs) are one of the most available and commercially distributed nanomaterials around the world. In order to understand how human health can be affected by SNPs, quantification and detection of SNPs in biological systems have to be conducted in different models. It seems that respiratory and gastrointestinal systems as well as the skin are the major routes of SNPs penetration into the body. Research on SNPs toxicity is mostly conducted in vitro, and the available human and animal data are relatively limited. This review attempts to focus on the characterization and quantification of the potential harmful effects of SNPs on human health.

Long-term exposure to even low levels of H2S in workplaces may have potential harmful effects on human health.

The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0.01nM-1 µM) alone or in combination with 50 nM of the CYP1A1 inhibitor 3'methoxy-4'nitro-flavone (MNF). CYP1A1 enzyme activity, cell viability, oxidative stress, and several endpoints of apoptosis were measured. FICZ treatment at a high concentration or in combination with MNF induced sustained CYP1A1 activity and led to oxidative stress and activation of apoptosis via a mitochondrial-dependent pathway. In comparison with the wild-type Hepa-1 cells, c37 cells lacking CYP1A1 activity proliferated faster in normal medium which contains trace levels of FICZ. Besides, in HepG2 cells, FICZ stimulated cell growth at low concentrations but inhibited cell growth at high concentrations. Based on these findings, we propose that CYP1A1 inhibitors, by increasing the levels of the endogenous ligand FICZ, change the cell growth kinetics and trigger cell death and apoptosis through a mitochondrial-dependent pathway. Since AHR controls multiple cellular functions, a wide range of toxicity can be expected by disturbing its endogenous functions.