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. 2022 Jun 25;38(4):557–566. doi: 10.1007/s43188-022-00137-1

Protective role of selenium on structural change of human hemoglobin in the presence of vinyl chloride

Negar Hajimohammadi Oushani 1, Masoumeh Valipour 2, Parvaneh Maghami 1,✉
PMCID: PMC9532497  PMID: 36277367

Abstract

Vinyl chloride is a colorless gas with a pleasant odor capable of entering the body through oral or inhalation routes. Extensive studies on this compound indicated that it is a carcinogen, and Vinyl chloride exposure can result in a specific type of cancer in vinyl chloride workers. Whereas hemoglobin plays a vital role in oxygen transfer throughout the body, in a molecular aspect, the effect of vinyl chloride on human hemoglobin has not been studied. Furthermore, selenium as an antioxidant is a vital factor for the health of humans and animals. Then this research investigated the effect of the antioxidant capability of selenium at the same concentrations in blood on the interaction between vinyl chloride and hemoglobin. UV–visible, Fourier-transform infrared, chemiluminescence, and fluorescence spectroscopies were employed. The results indicated the destruction of hemoglobin structure in different concentrations of vinyl chloride. At the same time, the antioxidant effect of selenium inhibited the destructive impact of vinyl chloride on hemoglobin structure.

Keywords: Chemiluminescence, Reactive oxygen species, Hemoglobin, Vinyl chloride

Introduction

Vinyl chloride (VC), or Vinyl chloride monomer (VCM), is a colorless gas that is a highly applied chemical in the plastic industry and has been considered an environmental pollutant [1, 2]. VC is employed in the plastic industry and polyvinyl chloride (PVC) production [3, 4]. Furthermore, VCs are found in cigarette smoke and some underground waters that have been subjected to biodegradation by bacterial processes [5–8]. VC is considered a carcinogen in humans because of numerous reports of liver disease in people exposed to the compound [1]. Exposure to VC causes angiosarcoma of the liver and hepatocellular carcinoma [9]. Workers exposed to VC monomer have been reported to lead to diseases such as fibrosis of the liver, portal hypertension, and liver angiosarcoma [10]. VC enters the body through inhalation or oral routes, which can cause errors in transcription and deletion or changes in genetic information.

Moreover, numerous studies have shown that exposure to significant amounts of VC results in DNA single-strand breaks, which are generally assumed to be inaccessible to repair [11]. Over the last 60 years, the study of human hemoglobin has increased more than any other molecule [7]; it can be better to assess the effects of VC on the human body. Hemoglobin is one of the essential proteins in the body that plays a vital role in transmitting oxygen, which is present in human and animal red blood cells in high concentrations [12]. Hemoglobin is a globular protein with a diameter of 5.5 nm and is a tetramer protein with four heme prosthetic groups for each polypeptide chain. In adults, hemoglobin is composed of two α chains and two β chains with three-dimensional structures [12, 13]. The α helices comprise 75 of the hemoglobin polypeptide chains structure, which is adjacent to the heme in a way that prevents heme exposure to the water molecules and, therefore, the formation of a suitable packet for heme attachment to the oxygen [14, 15]. No molecular studies have yet reported VC's effect on human Hemoglobin. Selenium (Se) is a required trace element involved in the complex system of defense against oxidative stress via selenium-dependent glutathione peroxidases (GPx) and plays a pivotal role in human fertility [16].

Se is a valuable mineral element for humans and animals whose deficiency results in various diseases such as reduced immune function. Additionally, it has a beneficial effect on the toxicity caused by chemical factors such as heavy metals [14, 15, 17, 18]. Because cell-reproduction and death are related to cell cycle control and apoptosis, Se is considered a cell cycle and apoptosis regulating agent and, consequently, important in preventing cancer [17]. As mentioned above, a specific type of liver cancer occurs due to VC exposure. However, according to the studies, many cancers can be prevented and controlled using appropriate antioxidants in the diet [18]. Based on a previous study, Se plays a moderating role in the effect of the pollutant on the liver and prevention of hepatic necrosis [19]. The current study attempted to address the moderating effect of Se on the destruction of hemoglobin structure in the presence of VC.

Materials and methods

Materials

Vinyl chloride monomer (VCM) (100 mg, 99.5% purity) was purchased from Sigma Chemical Co. (Darmstadt, Germany) as a colorless liquid. Hemoglobin was isolated and purified from human blood in the biochemistry and Biophysics University of Tehran laboratory. The protein was stored in a sterile vial in a − 50 °C freezer for future uses. Dipotassium hydrogen phosphate (K2HPO4), hydrochloric acid (HCl), Luminol, and Hydrogen peroxide 30%, used in the chemiluminescence assay, were obtained from Merck (Darmstadt, Germany).

Method

Purification of Human Hemoglobin

Adult hemoglobin (HbA) was isolated from red blood cells. Blood containing heparin was centrifuged to separate plasma. The red blood cells were washed three times using 0.9% saline, and then the red blood cells were lysed through osmosis using double distilled water, and the cell membrane was destroyed. The membrane components were separated employing 3000 rpm centrifugation. The hemoglobin solution was centrifuged two times at 10,000 rpm to remove the insoluble parts. The 20% ammonium sulfate was added to the supernatant. It was then incubated for 15 min, followed by centrifugation at 20,000 rpm at 2 °C for 2 h [20]. Diphosphoglycerate was removed using a method by Benesch et al. [21]. The obtained hemoglobin was dialyzed against 50 mM phosphate buffer (pH 7.4). Finally, the purified hemoglobin was maintained in the freezer to prevent destruction [22].

UV–visible spectroscopy

The T92 + UV Spectrophotometer (PG INSTRUMENTS, England) was employed in the current study. Phosphate buffer (0.5 M, pH 7.4), hemoglobin solution (1.3 mg/ml), and Se (1 ppb) were prepared and used. The effect of various concentrations of VCM on the structure and absorption of hemoglobin was studied. The experiment at first was established in finding hemoglobin structure, then titrations of hemoglobin solution with different concentrations of VCM. The titrations were tested in the presence of Se, and the effect of Se on the interaction between hemoglobin and VCM was investigated in the range of 200–700 nm. The absorbance values were explained between 250 and 600 nm.

Attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR)

ATR is used in infra-red spectroscopy to increase accuracy. ATR accessory in FTIR eliminates the need for producing a pellet for analysis. Thermo Nicolet Fourier Transform Infrared Spectrophotometer (Thermo Fisher Scientific, USA) was used for ATR-FTIR measurements. In this test, the desired amount of VCM was added to the hemoglobin solution in the presence or absence of Se.

Fluorescence spectroscopy

Cary Eclipse Fluorescence Spectrophotometer (Varian, Australia) was used in fluorescence measurements. Briefly, the VCM solution with the desired concentration was added to the hemoglobin solution (1.3 mg/ml in 10 mM phosphate buffer pH 7.4) in the presence or absence of Se (1 ppb). The excitation wavelength was 280 nm, and the emission intensities were recorded between 300 and 500 nm.

Chemiluminescence assay

Chemiluminescence assay was applied to measure and calculate the level of reactive oxygen species (ROS). Synergy H4 Hybrid Multi-Mode Plate Reader (BioTek Instrument, USA) was employed in the present study. In this essay, the amount of produced ROS upon the interaction of hemoglobin with VCM in the presence or absence of Se was measured. Briefly, Luminol was solubilized in the phosphate buffer, and the desired concentration of 0.0005 M was added to all the solutions in the plate. Chemiluminescence data was gathered at 430 nm after brief mixing. The measurements were repeated at least three times. Finally, the level of reactive oxygen species was calculated according to the H2O2 standard curve.

Molecular docking of hemoglobin- VCM

Molecular docking examinations were done by AutoDock Tools 4.2. To dock hemoglobin with the ligand (VCM), a three-dimensional protein structure was gained from PDB (Protein Data Bank): (https://doi.org/10.2210/pdb2DN1/PDB), and VCM got from the PubChem database (PubChem CID:6338). The structure of hemoglobin was modified by the addition of hydrogen atoms and the removal of water molecules using the Molegro Virtual Docker. A docking examination was run 10 times, and the minimum energy complex of protein-VCM was selected as the most stable one. LigPlot v.1.4 was applied to determine the type of interactions involved in the complex.

Results

UV–visible analysis

Figure 1 shows UV–Visible spectra (250–350 nm) of hemoglobin before and after VCM addition to the protein solution. As the data shows, the absorbance of hemoglobin samples was gradually increased by VCM addition. Protein has two deterministic UV–Vis peaks, one in the spectral region between 200 and 230 nm and the second between 230 and 300 nm. The first one happens in peptide bonds due to π–π*. The second one results from the absorbance of three aromatic residues by their presence in the protein and structure. The last one is more practical in protein–ligand interactions because their absorbance alters upon ligand binding. Since hemoglobin contains the heme prosthetic group, another peak is seen at around 412 nm, called soret band. Figure 2 represents the changes in soret region absorbance in the absence and presence of different VCM concentrations. The absorbance of soret band (around 412 nm) was deduced after VCM titration to hemoglobin samples. This demonstrates the interaction of VCM with heme group. The absorbance of the Q band is observed in Fig. 3. Q band stands for porphyrin rings. There are two Q bands in hemoglobin named α and β bands, with the absorbance at about 540 and 580 nm, respectively. Q band is considered a good indicator for the ligand-porphyrin interaction. The intensity of the protein samples was increased due to VCM addition. So VCM can change porphyrin absorbance by interfering with its interactions. These data confirm that VCM alters the absorbance properties of hemoglobin by changing the environmental condition of the protein.

Fig. 1.

Fig. 1

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UV–Vis spectra of 1.3 mg/ml hemoglobin dissolved in phosphate buffer pH 7.3 at 25 °C in the absence and presence of different VCM concentrations (from 0 to 3.15 µM). The absorbance of the samples was scanned from 250 to 350 nm. As shown by the arrow, the absorbance of hemoglobin was increased after VCM addition to the sample solution. Changes in the environment of the aromatic amino acid residues of hemoglobin have caused these changes.Hb stands for hemoglobin in the figure guide

Fig. 2.

Fig. 2

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Soret band absorbance of hemoglobin (1.3 mg/ml) before and after VCM addition (0 to 3.15 µM). The samples were prepared in phosphate buffer pH 7.3 at 25 °C. The absorbance of the samples was scanned from 350 to 500 nm. Soret band absorbance at around 412 nm decreased upon interaction with VCM. The arrow shows this reduction. Absorbance reduction is due to changes in heme group interactions induced by VCM. Hb stands for hemoglobin in the figure guide

Fig. 3.

Fig. 3

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Q band absorbance of hemoglobin (1.3 mg/ml) before and after VCM addition (0 to 3.15 µM). The samples were prepared in phosphate buffer pH 7.3 at 25 °C. The absorbance of the samples was measured from 500 to 600 nm. As shown by arrows, the Q band absorbance around 450 and 580 nm was increased upon interaction with VCM. So the globin interaction is affected by VCM addition. Hb stands for hemoglobin in the figure guide

Figure 4 shows the effect of Se on hemoglobin conformation upon interaction with VCM.. The UV–Vis spectra of four samples were recorded, including hemoglobin + Se, hemoglobin + VCM, and hemoglobin + Se + VCM. The experiment applied the concentration of 1 ppb Se and 200 µl VCM. Data represents that VCM has changed hemoglobin absorbance peaks at 280, 412, 540, and 480 nm. VCM has harmful effects on hemoglobin structure and has altered its interactions due to aromatic residues environment, heme group, and porphyrin surroundings. However, hemoglobin + Se + VCM graph shows the protective role of Se on hemoglobin conformational changes induced by VCM. The corresponding graph is similar to the native hemoglobin spectrum.

Fig. 4.

Fig. 4

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UV–Vis spectra of 1.3 mg/ml hemoglobin samples including Hb alone, Hb + 0.4 μM Se, Hb + 1.4 µM VCM and Hb + 0.4 μM Se + 1.4 µM VCM. All samples were dissolved in phosphate buffer pH 7.3 at 25 °C. The absorbance of the samples was scanned from 200 to 700 nm. Hb represents hemoglobin. Also, VCM could alter the environmental condition of hemoglobin and affect its interactions (VCM has changed hemoglobin absorbance peaks at 280, 412, 540, and 480 nm). Still, Se was able to protect against these harmful effects. The graph shows that hemoglobin spectra are similar before and after Se addition. The arrows show the similarity of the hemoglobin peaks before and after Se addition at 280, 412, 540, and 480 nm, respectively

ATR-FTIR analysis

FTIR spectroscopy was applied to estimate changes in protein secondary structure after VCM and Se addition. Based on the ATR-FTIR test demonstrated in Fig. 5, there was no displacement in the spectra in the regions of helices and β-sheets after Se and VCM addition. According to the spectra, the deterministic peak of hemoglobin secondary structure of hemoglobin is in the wavenumber range of 1600–1700 cm−1. Higher spectra intensity was seen for Se and VCM treated samples, but there was no wavenumber displacement. There were no significant changes in hemoglobin secondary structure after and before VCM and Se addition.

Fig. 5.

Fig. 5

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ATR-FTIR spectra of hemoglobin before and after Se and VCM addition. The spectra were gathered for samples prepared in phosphate buffer pH 7.3 at 25 °C. 1.3 mg/ml hemoglobin was dissolved in phosphate buffer. Se and VCM amounts were 0.4 μM and 1.4 µM, respectively. Although there are changes in the transmittance of hemoglobin spectra after the addition of VCM and Se, the wavenumber of the spectra is similar (between 1600 and 1700 cm−1). So there were no significant changes in hemoglobin secondary structure. Hb stands for hemoglobin in the figure guide

Fluorescence spectroscopy analysis

Figure 6 shows tryptophan fluorescence intensity excited at 280 nm, and emission spectra were gathered from 300 to 400 nm (A). The maximum emission intensity was recorded at 340 nm and plotted in Fig. 6B. The data did not show a detectable fluorescence intensity change in the presence of Se while adding 1.4 µM VCM in the absence of Se increased the tryptophan emission intensity. The following two graphs present the effects of VCM and Se. Trp microenvironment changes after VCM addition, and fluorescence intensity of hemoglobin increases. This may cause conformational alterations of hemoglobin. But when Se is added to the hemoglobin sample, it protects the protein conformation induced by VCM.

Fig. 6.

Fig. 6

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a The change in hemoglobin intrinsic fluorescence intensity, excited at 280 nm in the absence and presence of Se, VCM, and Se + VCM. The emission spectra were collected between 300 and 400 nm. b Hemoglobin tryptophan emission at 340 nm before and after Se, VCM, and Se + VCM. The samples were prepared in phosphate buffer at room temperature. After adding VCM, the protective effect of Se can be clarified. As Trp intrinsic fluorescence showed, VCM causes structural changes in hemoglobin.. However, Se could prevent these conformational alterations. Hb stands for hemoglobin in the figure guide

ROS measurements

A chemiluminescence assay was conducted to measure the level of reactive oxygen species. According to the Fig. 7, the induced changes in the amount of reactive oxygen species are evident after adding Se to the hemoglobin solution in the presence of VCM. The ROS produced in hemoglobin containing the sample was about 0.64 µM. After adding the VCM to the hemoglobin sample, the ROS amount significantly increased up to 16.54 µM. Se effectively reduced ROS in the sample containing hemoglobin + Se + VCM up to 0.67 µM.

Fig. 7.

Fig. 7

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The changes in the level of ROS based on the H2O2 standard curve, in the absence and presence of vinyl chloride monomer (VCM) and Se. All samples were prepared in phosphate buffer pH 7.3 and 25 °C. According to the data, ROS generation increased in the presence of VCM, and Se could reduce ROS generation. Hb stands for hemoglobin in the figure guide

Molecular docking

The results by docking studies show that the ligand (VCM) binds to the protein through its hydrophobic region. Hemoglobin and VCM complex were bounded by − 2.4 kcal/mol binding energy. Figure 8 shows the schematic illustration of the hemoglobin- VCM complex. Figure 8 shows a 3D model of hemoglobin- VCM interaction at the binding site. Figure 9A shows the interaction sites between hemoglobin and ligand. Furthermore, Figure 9B shows the hydrophobic interactions and the amino acids involved in hemoglobin- VCM interaction.

Fig. 8.

Fig. 8

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Schematic illustration of hemoglobin and VCM complex. 3D model of hemoglobin secondary structure and the interaction of hemoglobin- VCM are shown in the binding site. VCM is shaped as colored spheres, and a blue helix shows hemoglobin structure. Heme prosthetic group at the binding site is also indicated by pink color

Fig. 9.

Fig. 9

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a Interaction sites between hemoglobin and VCM: VCM is noticed by the green color at the center of the complex. It is demonstrated that residues Ala 27, Leu 106, Lue 110, Phe 71, Lue 68, Val 67, and Gly 24 are involved in the hemoglobin VCM interaction. b Hydrophobic interactions and the amino acids involved in hemoglobin- VCM interaction: VCM is depicted by black and green spheres linked through blue bonds. Hydrophobic interactions between VCM and the binding site of hemoglobin are delineated by red dashed lines

Discussion

VCM has been considered the first group of carcinogenic agents for humans by the International Agency for Research on Cancer [23–28].The capability of hemoglobin to bind oxygen depends onthe heme prosthetic group. Besides, this group is responsible for the red color of blood [29–31]. Therefore, preserving the hemoglobin structure is necessary to transfer oxygen to the organs and cells in the body. In this study, the effect of VCM on structural changes in hemoglobin was first investigated by UV–Vis experiments shown in Fig. 1; it is clear that the absorbance of the protein samples increased at 280 nm after VCM addition. The absorbance at 280 nm is due to aromatic amino acids (Trp, Tyr, and Phe). These amino acids, especially Trp residues of hemoglobin, are the main reporters of the protein environment. So the increase of spectra absorbance at 280 nm stands for hemoglobin environment alterations. Absorption was measured at 412 nm to assess whether the hemoglobin prosthesis group was affected by VCM. Figure 2 indicates the gradual reduction of soret band (412 nm) by VCM titration to the hemoglobin samples. The decreased absorption in the peak at around 412 nm demonstrated the loss of interaction between heme group and globin and heme degradation [32, 33]. Based on our observation in Fig. 2, it is noticeable that hemoglobin tertiary structure has changed due to interaction with VCM. Figure 3 represents the hyperchromicity effect of VCM in the region of 500 to 600 nm or Q bands of hemoglobin, which approve the binding of oxygen to the heme group. The increased absorbance of Q bands in the presence of VCM is related to the alterations of oxy-hemoglobin form due to interaction with VCM [34]. Figures 1, 2, and 3 confirm that VCM can induce conformational alterations in hemoglobin and disturb its interactions based on changes in UV–Vis intensities. So VCM can interfere with oxy-hemoglobin interactions and affect its oxygen binding and transport. However, it was a great idea to find a way to deduce side effects. To inhibit the harmful effects of VCM on hemoglobin structure, Se, as an antioxidant, was selected to reduce the structural changes in hemoglobin. Se has been shown to act as general preventive medicine in oncology [35]. It is incorporated into antioxidant enzymes as selenocysteine in the structure of glutathione oxidase and regulates glutathione activity, increases free radicals, and causes detoxification [36–39]. Se can also reduce oxidative stress induced by cadmium in plants [40]. This study aims to determine the effect of Se on hemoglobin titrated by VCM from a molecular point of view in vitro. It was revealed that Se alone did not induce changes in the hemoglobin structure. Besides, the inhibitory effect of Se on the structural destruction of VCM-induced hemoglobin was obvious (Fig. 4). Moreover, secondary structural changes in hemoglobin were studied using ATR-FTIR. The two regions of FTIR spectra, namely amid I and II bands, are suitable to detect protein secondary structure. Amide I represents C=O bond stretch around 1650 cm−1, and amide II stands for N–H bending vibrations (around 1550 cm−1) under neighboring CO, CC, and NC groups. These bonds take part in protein secondary structure by forming hydrogen bonds. Their vibration pattern demonstrated as amide I and II bands, which determined protein secondary structure [41, 42]. ATR-FTIR data shown in Fig. 5 indicates no changes in hemoglobin secondary structure content because wavelength shift was not seen in the presence of VCM and Se. The result monitored by fluorescence spectroscopy (Fig. 6) showed the increased intensity of hemoglobin in the presence of VCM. It means that the Trp emission wavelength is affected by the polarity of the micro-environment. So the interaction between VCM and Trp residue induces changes in hemoglobin conformation. This result is in the line of soret band absorbance measurement in Fig. 2. Based on Figs. 2 and 6,VCM could alter hemoglobin conformation. However, the addition of Se to the protein solution showed a protective effect on hemoglobin conformational change induced by VCM (Figs. 4 and 6A). Assessed by chemiluminescence experiments, adverse effects of VCM on hemoglobin were related to ROS generation. Oxidative stress conditions may damage macromolecules such as proteins via protein oxidation and cause protein conformational diseases like Alzheimer's, Parkinson's, etc. [43–45]. Furthermore, Fig. 7 showed that the presence of Se vastly reduced the ROS production of hemoglobin- VCM solution. So that the antioxidant effect of Se could protect the integrity of hemoglobin in the presence of VCM. Finally, a molecular docking examination was done to determine the interaction involved in the hemoglobin- VCM complex (Fig. 8). Results in Fig. 9A and B show that hemoglobin and VCM bind via hydrophobic interactions. Val, Ala, Leu, Phe, and Gly are the main residues in the mentioned hydrophobic interaction. According to the findings, VCM destroyed hemoglobin structure by producing ROS, ROS, and the presence of Se as an antioxidant inhibits the destroying effect of VCM on hemoglobin. Since oxygen-binding depends on the heme prosthetic group, any change in heme structure leads to lower oxygen-binding, which means a lower oxygenation rate of the various tissues and organs.Thus, Se is a suitable ROS scavenger in the case of the hemoglobin-VCM study. However, more studies are needed to discover the generality of Se deleterious effect in molecular level studies.

Acknowledgements

This paper and the research behind it would not have been possible without the exceptional support of my colleges at Zakariaye Razi Laboratory Complex, Science and Research Branch, Islamic Azad University

Abbreviation

VCM

Vinyl chloride monomer

Author contributions

PM: conceptualized and designed the study, collected the data, interpreted and analyzed the data, provided contributions and critically revised the manuscript, and gave final approval of the version to be published. NHO: collected the data, interpreted and analyzed the data, drafted the manuscript and provided contributions and critically revised the manuscript, and gave final approval of the version to be published. MV: interpreted and analyzed the data, critically revised the manuscript, and gave final approval of the version to be published.

Funding

This study was unfunded.

Data availability

All relevant data included in this manuscript.

Declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study included searching and reviewing only publicly available information online. There was no need for ethical approval.

Consent to participate

Not applicable.

Consent for publication

All authors agree to publish this manuscript.

References

  • 1.Anders LC, Lang AL, Anwar-Mohamed A, Douglas AN, Bushau AM, Falkner KC, Hill BG, Warner NL, Arteel GE, Cave M, McClain CJ. Vinyl chloride metabolites potentiate inflammatory liver injury caused by LPS in mice. Toxicol Sci. 2016;151:312–323. doi: 10.1093/toxsci/kfw045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Reitze AW, Jr, Lowell R. Control of hazardous air pollution. BC Envtl Aff L Rev. 2000;28:229. [Google Scholar]
  • 3.Dogliotti E. Molecular mechanisms of carcinogenesis by vinyl chloride. Ann Ist Super Sanita. 2006;42:163. [PubMed] [Google Scholar]
  • 4.Oehha CA. Chloropicrin acute toxicity summary. Toxicol Lett. 1999 doi: 10.1016/j.toxlet.2020.01.022. [DOI] [Google Scholar]
  • 5.IARC Working Group on the Evaluation of the Carcinogenic Risk of Chemicals to Humans IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Food Chem Toxicol. 1979 doi: 10.1016/0278-6915(84)90103-0. [DOI] [Google Scholar]
  • 6.Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I. Vinyl chloride: still a cause for concern. Environ Health Perspect. 2000;108:579–588. doi: 10.1289/ehp.00108579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, Starr TB. Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment. Toxicol Sci. 2011;120:S130–145. doi: 10.1093/toxsci/kfq371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Anders LC, Yeo H, Kaelin BR, Lang AL, Bushau AM, Douglas AN, Cave M, Arteel GE, McClain CJ, Beier JI. Role of dietary fatty acids in liver injury caused by vinyl chloride metabolites in mice. Toxicol Appl Pharmacol. 2016;311:34–41. doi: 10.1016/j.taap.2016.09.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Wong RH, Chen PC, Du CL, Wang JD, Cheng TJ. An increased standardized mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan. Occup Environ Med. 2002;59:405–409. doi: 10.1136/oem.59.6.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Fedeli U, Girardi P, Mastrangelo G. Occupational exposure to vinyl chloride and liver diseases. World J Gastroenterol. 2019;25:4885–4891. doi: 10.3748/wjg.v25.i33.4885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Clewell HJ, Gentry PR, Gearhart JM, Allen BC, Andersen ME. Comparison of cancer risk estimates for vinyl chloride using animal and human data with a PBPK model. Sci Total Environ. 2001;274:37–66. doi: 10.1016/s0048-9697(01)00730-6. [DOI] [PubMed] [Google Scholar]
  • 12.Nagai M, Mizusawa N, Kitagawa T, Nagatomo S. A role of heme side-chains of human hemoglobin in its function revealed by circular dichroism and resonance Raman spectroscopy. Biophys Rev. 2018;10:271–284. doi: 10.1007/s12551-017-0364-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Perutz MF. Myoglobin and haemoglobin: role of distal residues in reactions with haem ligands. Trends Biochem Sci. 1989;14:42–44. doi: 10.1016/0968-0004(89)90039-x. [DOI] [PubMed] [Google Scholar]
  • 14.Vuletich DA, Falzone CJ, Lecomte JT. Structural and dynamic repercussions of heme binding and heme-protein cross-linking in Synechococcus sp. pcc 7002 hemoglobin. Biochemistry. 2006;45:14075–14084. doi: 10.1021/bi061532g. [DOI] [PubMed] [Google Scholar]
  • 15.Liong EC, Dou Y, Scott EE, Olson JS, Phillips GN., Jr Waterproofing the heme pocket: role of proximal amino acid side chains in preventing hemin loss from myoglobin. J Biol Chem. 2001;276:9093–9100. doi: 10.1074/jbc.m008593200. [DOI] [PubMed] [Google Scholar]
  • 16.Pieczyńska J, Grajeta H. The role of selenium in human conception and pregnancy. J Trace Elem Med Biol. 2015;29:31–38. doi: 10.1016/j.jtemb.2014.07.003. [DOI] [PubMed] [Google Scholar]
  • 17.Zeng H. Selenium as an essential micronutrient: roles in cell cycle and apoptosis. Molecules. 2009;14:1263–1278. doi: 10.3390/molecules14031263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Saha SK, Lee SB, Won J, Choi HY, Kim K, Yang GM, Dayem AA, Cho SG. Correlation between oxidative stress, nutrition, and cancer initiation. Int J Mol Sci. 2017;18:1544. doi: 10.3390/ijms18071544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Schwarz K, Foltz CM. Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. Nutr Rev. 1978;36:338–340. doi: 10.1111/j.1753-4887.1978.tb03701.x. [DOI] [PubMed] [Google Scholar]
  • 20.Hink WF, Briggs JD. Bactericidal factors in haemolymph from normal and immune wax moth larvae, Galleria mellonella. J Insect Physiol. 1968;14:1025–1034. doi: 10.1016/0022-1910(68)90011-5. [DOI] [Google Scholar]
  • 21.Benesch RE, Benesch R, Yu CI. Oxygenation of hemoglobin in the presence of 2, 3-diphosphoglycerate. Effect of temperature, pH, ionic strength, and hemoglobin concentration. Biochemistry. 1969;8:2567–2571. doi: 10.1021/bi00834a046. [DOI] [PubMed] [Google Scholar]
  • 22.Antonini E, Brunori M. Hemoglobin. Annu Rev Biochem. 1970;39:977–1042. doi: 10.1146/annurev.bi.39.070170.004553. [DOI] [PubMed] [Google Scholar]
  • 23.Hao JN, Xu XY, Lian X, Zhang C, Yan B. A luminescent 3d–4f-4d MOF nanoprobe as a diagnosis platform for human occupational exposure to vinyl chloride carcinogen. Inorg Chem. 2017;56:11176–11183. doi: 10.1021/acs.inorgchem.7b01549. [DOI] [PubMed] [Google Scholar]
  • 24.Brandt-Rauf PW, Li Y, Long C, Monaco R, Kovvali G, Marion MJ. Plastics and carcinogenesis: the example of vinyl chloride. J Carcinog. 2012;11:5. doi: 10.4103/1477-3163.93700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Fujiwara R. Exposure to sub-parts per million levels of vinyl chloride can increase the risk of developing liver injury. Hepatol Commun. 2018;2:227–229. doi: 10.1002/hep4.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Kumar AK, Balachandar V, Arun M, Ahamed SA, Kumar SS, Balamuralikrishnan B, Sankar K, Sasikala K. A comprehensive analysis of plausible genotoxic covariates among workers of a polyvinyl chloride plant exposed to vinyl chloride monomer. Arch Environ Contam Toxicol. 2013;64:652–658. doi: 10.1007/s00244-012-9857-1. [DOI] [PubMed] [Google Scholar]
  • 27.Ward E, Boffetta P, Andersen A, Colin D, Comba P, Deddens JA, De Santis M, Engholm G, Hagmar L, Langard S, Lundberg I. Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry. Epidemiology. 2001;1:710–718. doi: 10.1097/00001648-200111000-00021. [DOI] [PubMed] [Google Scholar]
  • 28.Huang PC, Liu LH, Shie RH, Tsai CH, Liang WY, Wang CW, Tsai CH, Chiang HC, Chan CC. Assessment of urinary thiodiglycolic acid exposure in school-aged children in the vicinity of a petrochemical complex in central Taiwan. Environ Res. 2016;150:566–572. doi: 10.1016/j.envres.2015.11.027. [DOI] [PubMed] [Google Scholar]
  • 29.Emadi M, Maghami P, Khorsandi K, Hosseinzadeh R. Biophysical study on the interaction of cartap hydrochloride and hemoglobin: heme degradation and functional changes of protein. J Biochem Mol Toxicol. 2019;33:e22325. doi: 10.1002/jbt.22325. [DOI] [PubMed] [Google Scholar]
  • 30.Chakraborty M, Paul S, Mitra I, Bardhan M, Bose M, Saha A, Ganguly T. To reveal the nature of interactions of human hemoglobin with gold nanoparticles having two different morphologies (sphere and star-shaped) by using various spectroscopic techniques. J Photochem Photobiol B Biol. 2018;178:355–366. doi: 10.1016/j.jphotobiol.2017.11.026. [DOI] [PubMed] [Google Scholar]
  • 31.Minai-Tehrani D, Toofani S, Yazdi F, Minai-Tehrani A, Mollasalehi H, Ziabari KB. Inhibition of pseudoperoxiadse activity of human red blood cell hemoglobin by methocarbamol. Int J Biol Macromol. 2017;94:788–792. doi: 10.1016/j.ijbiomac.2016.09.049. [DOI] [PubMed] [Google Scholar]
  • 32.Valipour M, Maghami P, Habibi-Rezaei M, Sadeghpour M, Khademian MA, Mosavi K, Ahmad F, Moosavi-Movahedi AA. Counteraction of the deleterious effects of reactive oxygen species on hemoglobin structure and function by ellagic acid. J Lumin. 2017;182:1–7. doi: 10.1016/j.jlumin.2016.10.003. [DOI] [Google Scholar]
  • 33.Ariaeenejad S, Moosavi-Movahedi A, Kavousi K, Reza Dayer M, Hong J, Yousefi R, Sheibani N, Habibi-Rezaei M. The species and heme pocket properties of Sturgeon Hemoglobins upon interaction with N-dodecyl trimethylammonium bromide. Protein Pept Lett. 2014;21:171–178. doi: 10.2174/09298665113209990092. [DOI] [PubMed] [Google Scholar]
  • 34.Hosseinzadeh R, Moosavi-Movahedi AA. Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: a spectroscopic study. Spectrochim Acta A Mol Biomol Spectrosc. 2016;157:41–49. doi: 10.1016/j.saa.2015.12.014. [DOI] [PubMed] [Google Scholar]
  • 35.Cary L, Naveau A, Migeot V, Rabouan S, Charlet L, Foray N, Séby F, Bueno M, Jury C, Parmentier M, Louart J. From water-rock interactions to the DNA: a review of selenium issues. Procedia Earth Planet Sci. 2017;17:698–701. doi: 10.1016/j.proeps.2016.12.157. [DOI] [Google Scholar]
  • 36.El-Demerdash FM, Nasr HM. Antioxidant effect of selenium on lipid peroxidation, hyperlipidemia and biochemical parameters in rats exposed to diazinon. J Trace Elem Med Biol. 2014;28:89–93. doi: 10.1016/j.jtemb.2013.10.001. [DOI] [PubMed] [Google Scholar]
  • 37.Safhi MM, Alam MF, Khuwaja G, Ashafaq M, Khan A, Islam F, Anwer T, Khan G, Sivakumar SM, Islam F. Selenium in combination with tellurium protects the toxicity of tellurium in the liver mitochondria of rats. Bull Environ Pharmacol Life Sci. 2018;7:90–95. doi: 10.1016/j.jsps.2020.04.002. [DOI] [Google Scholar]
  • 38.Wrobel JK, Power R, Toborek M. Biological activity of selenium: revisited. IUBMB Life. 2016;68:97–105. doi: 10.1002/iub.1466. [DOI] [PubMed] [Google Scholar]
  • 39.Hatfield DL, Berry MJ, Gladyshev VN. Selenium: its molecular biology and role in human health. Springer; 2011. [Google Scholar]
  • 40.Zimmerman MT, Bayse CA, Ramoutar RR, Brumaghim JL. Sulfur and selenium antioxidants: challenging radical scavenging mechanisms and developing structure–activity relationships based on metal binding. J Inorg Biochem. 2015;145:30–40. doi: 10.1016/j.jinorgbio.2014.12.020. [DOI] [PubMed] [Google Scholar]
  • 41.Barth A. Infrared spectroscopy of proteins. Biochem Biophys Acta. 2007;1767:1073–1101. doi: 10.1016/j.bbabio.2007.06.004. [DOI] [PubMed] [Google Scholar]
  • 42.Calabrò EM, Magazù S. Unfolding-induced in haemoglobin by exposure to electromagnetic fields: an FTIR spectroscopy study. Orient J Chem. 2014;30:31–35. doi: 10.13005/ojc/300104. [DOI] [Google Scholar]
  • 43.Kim GH, Kim JE, Rhie SJ, Yoon S. The role of oxidative stress in neurodegenerative diseases. Exp Neurobiol. 2015;24:325–340. doi: 10.5607/en.2015.24.4.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Lévy E, El Banna N, Baïlle D, Heneman-Masurel A, Truchet S, Rezaei H, Huang ME, Béringue V, Martin D, Vernis L. Causative links between protein aggregation and oxidative stress: a review. Int J Mol Sci. 2019;20:3896. doi: 10.3390/ijms20163896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7:65–74. doi: 10.2174/157015909787602823. [DOI] [PMC free article] [PubMed] [Google Scholar]

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