The Protective Effects of Taurine, a Non-essential Amino Acid, Against Metals Toxicities: A Review Article.

Taurine is a non-proteinogenic amino acid derived from cysteine. It is involved in several phenomena such as the regulation of growth and differentiation, osmoregulation, neurohormonal modulation, and lipid metabolism. Taurine is important because of its high levels in several tissues such as the central nervous system (CNS), heart, skeletal muscles, retinal membranes, and platelets. In this report, we present the functional properties of taurine indicating that it has potential effects on various metal toxicities. Therefore, a comprehensive literature review was performed using the Scopus, PubMed, and Web of Science databases. According to the search keywords, 61 articles were included in the study. The results indicate that taurine protects tissues against metal toxicity through enhancement of enzymatic and non-enzymatic antioxidant capacity, modulation of oxidative stress, anti-inflammatory and anti-apoptotic effects, involvement in different molecular pathways, and interference with the activity of various enzymes. Taken together, taurine is a natural supplement that presents antitoxic effects against many types of compounds, especially metals, suggesting public consumption of this amino acid as a prophylactic agent against the incidence of metal toxicity.

Optimization and synthesis of a novel sorbent composite based on magnetic chitosan-amine-functionalized bimetallic MOF for the simultaneous dispersive solid-phase microextraction of four aflatoxins in real water, herbal distillate, and food samples.

Aflatoxins (AFs), an important category of pollutants, are formed in many foods and adversely affect human health. Therefore, their determination is critical to ensuring human food health. An efficient dispersive solid-phase microextraction technique was developed as a simple and straightforward sample preparation technique for determination of four aflatoxins using a high-performance liquid chromatography (HPLC) fluorescence detector. A novel efficient, green sorbent for extracting AFs was synthesized based on hydrothermal and chemical strategies. The amounts of three sorbent components were optimized using a mixture design (simplex lattice design), including 14 experiments. The optimal amount of amino-bimetallic Fe/Ni-MIL-53 nanospheres, chitosan, and magnetic Fe3O4 nanoparticles as sorbent components was 0.87, 0.67, and 0.47 g, respectively. Also, various factors affecting the process of AF determination were studied and optimized in two successive experimental designs, including the definitive screening design and the Box-Behnken design. Under optimal conditions, the linear ranges for measuring aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 were 0.05-82.6, 0.07-86.4, 0.08-85.7, and 0.07-89.5 ng mL-1, respectively. The relative standard deviations under inter-day and intra-day conditions for measuring AFs at three analyte concentrations were determined in triplicate analysis and were in the ranges of 3.7-4.6% and 4.9-6.1% for water sample analysis, respectively. The qualitative detection limits for determining AFs were between 0.01 and 0.05 ng mL-1. The pre-concentration factor of the method for measuring AFs ranged from 739.7 to 802.1. The proposed method was used for determining AFs in several real samples, including herbal distillate, black tea, corn, and real water samples. The relative recovery and standard deviation were 87.8-97.8% and 4.10-6.82%, respectively.

Developments of Microextraction (Extraction) Procedures for Sample Preparation of Antidepressants in Biological and Water Samples, a Review.

Antidepressants are an important class of drugs to treat various types of depression. The determination of antidepressants is crucial in biological samples to control adverse effects in humans and study pharmacokinetics and bioavailability. Direct measurement of antidepressants in biological and water samples is a considerable challenge for analysts due to their low concentration, the high matrix effects of real samples, and the presence of metabolites of these drugs in biological samples. The challenge leads to using sample preparation processes as a critical step in determining antidepressants. Extraction and microextraction procedures have been widely utilized as sample preparation procedures for these drugs. The purposes of extraction or microextraction methods for antidepressant medications are to preconcentrate the analyte, reduce the matrix effects, increase the selectivity of the procedures, and convert the sample to a suitable format for introducing it into detection systems. In the review, the various extraction and microextraction methods of these drugs in biological, real water, and wastewater samples were investigated. The theory of each technique was briefly addressed to understand the features and factors affecting each method. The extraction and microextraction methods were classified based on their application for antidepressants, and the advantages and disadvantages of each technique were reviewed. The new developments to overcome the limitations of each procedure were discussed. The investigation indicated the number of applications of liquid-phase microextraction for extracting antidepressants has been almost equal to that of solid-phase microextraction.

The interplay of aryl hydrocarbon receptor/WNT/CTNNB1/Notch signaling pathways regulate amyloid beta precursor mRNA/protein expression and effected the learning and memory of mice.

The amyloid beta precursor protein (APP) plays a pathophysiological role in the development of Alzheimer's disease as well as a physiological role in neuronal growth and synaptogenesis. The aryl hydrocarbon receptor (AhR)/WNT/Catenin Beta 1 (CTNNB1)/Notch signaling pathways stamp in many functions, including development and growth of neurons. However, the regulatory role of AhR-/WNT-/CTNNB1-/Notch-induced APP expression and its influence on hippocampal-dependent learning and memory deficits is not clear. Male BALB/C mice received 6-formylindolo[3,2-b]carbazole (an AhR agonist), CH223191(an AhR antagonist), DAPT (an inhibitor of Notch signaling), and XAV-939 (a WNT pathway inhibitor) at a single dose of 100 µg/kg, 1, 5 , and 5 mg/kg of body weight, respectively, via intraperitoneal injection alone or in combination. Gene expression analyses and protein assay were performed on the 7th and 29th days. To assess the hippocampal-dependent memory, all six mice also underwent contextual fear conditioning on the 28th day after treatments. Our results showed that endogenous ligand of AhR has a regulatory effect on APP gene. Also, the interaction of AhR/WNT/CTNNB1 has a positive regulatory effect, but Notch has a negative regulatory effect on the mRNA and protein expression of APP, which have a correlation with mice's learning skills and memory.

Evaluation of oxidative stress and biochemical biomarkers, and psychological parameters in cement plant workers.

The cement industry is one of the main world industries with exposure to a wide range of hazardous chemical and physical occupational agents that may increase free radicals and lead to disease. The aim of this study was to evaluate oxidative stress, biochemical markers, and psychological parameters among cement plant workers. In this cross-sectional study, 40 workers exposed to cement and 40 office employees were selected as the exposed and non-exposed groups, respectively. Exposure to cement dust, silica, and noise were, respectively, assessed using the NIOSH 0600, NIOSH 7601, and noise dosimetry methods. Oxidative stress biomarkers including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and biochemical parameters were measured in the serum of all participants. Depression, anxiety, and stress were assessed by the Depression Anxiety Stress Scales (DASS-21) questionnaire. The results demonstrated that the level of MDA as a marker of oxidative stress was significantly higher in the exposed group. The level of antioxidant enzymes including SOD and CAT were also significantly higher in the exposed group. The level of TAC was lower in the exposed group, but the difference was not statistically significant. The levels of alkaline phosphatase (ALP), aspartate transaminase (AST), and the scores of depression and stress were also significantly higher in the exposed group. According to our results, noise, cement dust, and silica exposure were associated with oxidative stress, and this may be one of the mechanisms in which they adversely affect liver function and mental health.

Anticancer properties of vincristine is modulated by microRNAs in acute lymphoblastic leukemia Nalm6 cell line.

Precursor B-cell acute lymphoblastic leukemia (B-ALL), a highly diverse disease, is the most widespread pediatric malignancy characterized by cytogenetic and molecular abnormalities such as altered microRNA (miR) expression signatures. MiRs are a class of short noncoding RNAs. Dysregulation in the expression of miRs plays a crucial role in different types of cancers. Vincristine is an antineoplastic drug with a broad spectrum of activity against different hematologic malignancies and is the first-line treatment for B-ALL. Previous studies have proposed miR-17 and miR-181/b as oncomirs and miR-34/a as a tumor suppressor in Nalm6 cells, thus in the current study, we investigated the effects of vincristine treatment on the expression of miR-17, miR-34/a and miR-181/b expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was conducted to estimate the optimal concentration of vincristine in the Nalm-6 cell line. Expression of miRs was calculated using real-time PCR. Our results showed significant downregulation of miR-17 (FC = 0.226; P < 0.0004) in Nalm6 cells after vincristine treatment. Conversely, miR-34/a (FC = 4.823; P < 0.0001) was significantly upregulated. Also, the expression of miR-181/b (FC = 0.156; P < 0.3465) was not significantly different between the vincristine treated group and the control group. In conclusion, it is proposed that one of the mechanisms by which vincristine improves B-ALL is by modulating the expression of specific miRs. These specific miRs will serve as good diagnostic and prognostic biomarkers.

Influence of cellular redox environment on aryl hydrocarbon receptor ligands induced melanogenesis.

Many environmental pollutants, natural compounds, as well as endogenous chemicals exert their biological/toxicological effects by reacting with the aryl hydrocarbon receptor (AhR). Previous evidence shed new light on the role of AhR in skin physiology by regulating melanin production. In this study, we investigated the effect of oxidative imbalance induced by AhR ligands on the melanogenesis process in B16 murine melanoma cells. Exposure to 6-formylindolo[3,2-b] carbazole (FICZ) or benzo-α-pyrene (BαP) led to enhanced expression of CTNNB1, MITF, and TYR genes following increased tyrosinase enzyme activity and melanin content in an AhR-dependent manner. Analysis of the presence of reactive oxygen species (ROS) as well as reduced glutathione (GSH) / oxidized glutathione (GSSG) ratio revealed that treatment with AhR ligands is associated with oxidative stress which can be ameliorated with NAC (N-acetyl cysteine) or diphenyleneiodonium chloride (DPI). On the other hand, NAC and DPI enhanced melanogenesis induced by AhR ligands by reducing the level of ROS. We have shown for the first time that a cellular redox status is a critical event during AhR ligand-induced melanogenesis.

Simultaneous determination of organophosphorus pesticides residues in vegetable, fruit juice, and milk samples with magnetic dispersive micro solid-phase extraction and chromatographic method; recruitment of simplex lattice mixture design for optimization of novel sorbent composites.

Dispersive micro solid-phase extraction procedure using a novel and selective sorbent prepared from four components was developed as a sample preparation strategy for extracting five organophosphorus pesticides, including fenitrothion, malathion, ethion, and chlorpyrifos, and diazinon in several vegetables, fruit juices, and cow's milk samples. Due to the high importance of the sorbent in the microextraction process, the percentages of sorbent components, including metal-organic framework (ZIF-67), chitosan, magnetic Fe3O4 nanoparticles, and silica nanoparticles, were optimized by a simplex lattice mixture design. After optimizing the sorbent composite, effective parameters on the extraction of organophosphorus pesticides were optimized using a definitive screening design and Box-Behnken design, respectively. A surfactant (Triton X100) as a dispersion agent with a low volume (10 µL) was utilized in the microextraction procedure to reduce the sorbent dispersion time and increase the sorbent dispersion efficiency. Under the optimal conditions, linearity for the determination of fenitrothion, malathion, ethion, chlorpyrifos, and diazinon was in the concentration ranges of 0.13-1100, 0.27-1000, 0.38-1000, 0.21-1200, and 0.11-1100 ng mL-1 with a determination coefficient higher than 0.9906, respectively. The quantitation limits, detection limits, and relative standard deviations (n = 5) were lower than 0.38 ng mL-1, 0.11 ng mL-1, and 4.59% for the determination of organophosphorus pesticides. The method application for measuring OPPs on cucumber, carrot, tomato, apple juice, orange juice, and cow's milk indicated the presence of residual amounts of malathion in a cucumber sample, diazinon in a carrot sample, and chlorpyrifos in a tomato sample.

Aryl hydrocarbon receptor engagement during redox alteration determines the fate of CD4+ T cells in C57BL/6 mice.

The preservation of the redox homeostasis is critical for cell survival and functionality. Redox imbalance is an essential inducer of several pathological states. CD4+ /helper T cells are highly dependent on the redox state of their surrounding milieu. The potential of the aryl hydrocarbon receptor (AhR) engagement in controlling CD4+ T-cell fate during redox alteration is still challenging. C57BL/6 mice were treated with AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ), AhR antagonist CH223191, an inhibitor of glutathione biosynthesis buthionine sulfoximine (BSO), and the antioxidant N-acetylcysteine (NAC) alone or in combination. Six days later, splenocytes were evaluated for the expression of the redox-related genes and the possible changes in T-cell subsets. FICZ like BSO significantly elevated the expression of HMOX1, GCLC, and GCLM genes but it failed to increase the expression of the Nrf2 gene. Moreover, FICZ + BSO increased while FICZ + CH223191 or NAC decreased the expression of these genes. FICZ also significantly increased Th1 cell numbers but decreased Tregs in a dose-dependent manner. Furthermore, a high dose of FICZ + CH223191 + NAC significantly enhanced Th1, Th17, and Treg cells but its low dose in such a situation increased Th2 and Th17 while decreased Treg cells. AhR engagement during redox alteration can determine the fate of CD4 + T cells, so, AhR agonists or antagonists might be useful in assessing immune responses. However, these results need further verifications in vitro and in animal models of various diseases.

α-Melanocyte-Stimulating Hormone Triggers Melanogenesis Via Activation of the Aryl Hydrocarbon Receptor Pathway in B16F10 Mouse Melanoma Cells.

Melanin is a group of natural pigments that determines the human skin color and provides fundamental protection against the harmful impacts of physical and chemical stimuli. The aim of this study was to establish the regulatory role of aryl hydrocarbon receptor (AhR) in α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis. In the present study, following knockdown of AhR, murine B16F10 cells were treated with α-MSH (200 nM) and tyrosinase activities, cellular melanin content, mRNA levels of several important genes involved in melanogenesis including AhR, CTNNB1, TYR2, and microphthalmia-associated transcription factor (MITF) were measured as endpoints. Exposure to α-MSH led to elevated expression of AhR, CTNNB1, MITF, and TYR in accordance with increased tyrosinase enzyme activity as well as a significant rise in the total melanin content. Our results suggest that AhR plays a regulatory role in α-MSH-stimulated melanogenesis.

An Endogenous Ligand of Aryl Hydrocarbon Receptor 6-Formylindolo[3,2-b]Carbazole (FICZ) Is a Signaling Molecule in Neurogenesis of Adult Hippocampal Neurons.

Neurogenesis is a dynamic and physiologic developmental process that affects learning and hippocampal dependent memory. It is regulated by multi-cellular micro-environment and different types of transcription factors. The neurogenesis effects of endogenously activated aryl hydrocarbon receptor (AHR) by its endogenous ligand, 6-formylindolo[3,2-b] carbazole (FICZ), and its interactions with the Wnt/ß-catenin signaling pathway were the main purpose of this study. In accordance, learning and hippocampus-dependent memory were examined. Male BALB/C mice received FICZ, CH223191, and XAV-939 in a single dose of 100 µg/kg, 1 mg/kg, and 5 mg/kg of body weight respectively via intraperitoneal (IP) injection. qRT-PCR for gene analyses and protein assay on the 7th and 28th days were performed. To assess the hippocampal dependent memory, they also underwent contextual fear conditioning on the 28th day after treatment. Our results showed that FICZ treatment led to elevation of the proneural transcription factors ASCL1 and Ngn2, immature neural marker DCX, differentiation neurons marker, NeuN, as well as ß-catenin at mRNA and protein levels. We also indicated that hippocampal dependent memory and learning task were improved by FICZ treatment and impaired by the AHR and Wnt/ß-catenin inhibition. In this study for the first time, we demonstrated that the endogenous ligand of AHR, FICZ, has a positive effect on short- and long-term memory as well as learning skills. This ability is possibly mediated by the AHR-Wnt/ß-catenin cross-talk.

Selective cytochrome P450 1A1 but not 1B1 promoterCpG island DNA methylation by 6-formylindolo[3,2-b]carbazole (FICZ).

Epigenetic alterations are essential for normal mammalian development and regulation of gene expression. In this study, we aimed to determine if an enigmatic endogenous ligand of the aryl hydrocarbon receptor (AHR), 6-formylindolo[3,2-b]carbazole (FICZ), and methionine (Meth) have an epigenetic impact on AHR-regulated cytochrome P450 1A1 and B1 (CYP1A1 and CYP1B1) gene expression. Human hepatoma (HepG2-XRE-Luc and huh7) cells were exposed to FICZ in a medium with and without Meth supplementation. Selective and transient silencing of CYP1A1 but not CYP1B1 were seen by FICZ. Here we found that FICZ transiently represses CYP1A1 by targeting DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and concomitant DNA methylation of the CYP1A1 promoter gene. Treatments with 5-aza-dC augmented CYP1A1 transcription activity. Our results reveal a new mechanism for transient activation of AHR by FICZ that can negatively and positively influence gene expression, and highlight the regulatory role of Meth on the CYP1A1 gene expression.

Aryl hydrocarbon-estrogen alpha receptor-dependent expression of miR-206, miR-27b, and miR-133a suppress cell proliferation and migration in MCF-7 cells.

The underlying functions of miR-206, miR-133a, miR-27b, and miR-21, and their link to the estrogen receptor alpha (ERα) and aryl hydrocarbon receptor (AhR) signaling pathways remain largely unexplored. In this study, we detect the expression of miR-206, miR-133a, miR-27b, and miR-21 in MCF-7 through quantificational real-time polymerase chain reaction assay along with the activation/inhibition of ERα and AhR receptors. Aside from this, cell proliferation and migration as well as AhR-dependent CYP1A1 enzyme activity were measured. Here, we found that the forced increased expression of miR-206, miR-133a, and miR-27b were closely associated with the suppression of MCF-7 cell proliferation and migration. The anti-proliferative-metastatic effect of miR-206, miR-133a, and miR-27b was probably mediated by targeting the ERα and AhR signaling pathways. Considered together, our study indicated that the overexpression of miR-206, miR-133a, and miR-27b might be potential biomarkers for prognosis and therapeutic strategies in breast cancer.

Hormesis Effects of Nano- and Micro-sized Copper Oxide.

The concerns about the possible risk of manufactured nanoparticles (NPs) have been raised recently. Nano- and micro-sized copper oxide (CO and CONP) are widely used in many industries. In this regard, in-vitro studies have demonstrated that CONP is a toxic compound in different cell lines. Despite their unique properties, NPs possess unexpected toxicity profiling relative to the bulk materials. This study was designed to examine and compare the toxic effects of CO and CONPs in-vivo and in isolated rat mitochondria. Male Wistar albino rats received 50 to 1000 mg/kg CO or CONP by gavage and several toxicological endpoints including biochemical indices and oxidative stress markers. Then, the pathological parameters in the multiple organs such as liver, brain, spleen, kidney, and intestine were assessed. Mitochondria were isolated from the rat liver and several mitochondrial indices were measured. The results of this study demonstrated that CO and CONP exhibited biphasic dose-response effects. CONPs showed higher toxicity compared with the bulk material. There were no significant changes in the results of CONP and CO in isolated rat liver mitochondria. The present studies provided more information regarding the hormetic effects of CO and CONPs in-vivo and in isolated rat mitochondria.