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Bisphenol S induced dysregulations in liver; iron regulatory genes and inflammatory mediators in male Wistar rats

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Abstract

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.

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Abbreviations

ALP:

alkaline phosphatase

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

BPA:

bisphenol A

BPS:

bisphenol S

D-I, D-II, D-III:

dose-I, dose-II, dose-III

HDL-C:

high density lipoprotein cholesterol

H&E staining:

hematoxylin and eosin staining

LDL-C:

low density lipoprotein cholesterol

VLDL-C:

very low density lipoprotein cholesterol

References

  • Abbasi MH, Akhtar T, Malik IA, Fatima S, Khawar B, Mujeeb KA, Mustafa G, Hussain S, Iqbal J, Sheikh N (2013) Acute and chronic toxicity of thioacteamide and alterations in blood cell indices in rats. J Cancer Ther 4(1):251–259

    Article  Google Scholar 

  • Abdel-Wahab WM (2014) Thymoquinone attenuates toxicity and oxidative stress induced by bisphenol A in liver of male rats. Pak J Biol Sci 17:1152–1160

    Article  CAS  Google Scholar 

  • Al-Rekabi BK, Al-Diwan MA, Sawad AA (2019) The protective role of CoQ10 and DHEA and their combination on CCl4 induced liver injury in adult male rats (Rattus norvegicus). J Biosci Appl Res 5:375–389

    Article  Google Scholar 

  • Ambreen S, Akhtar T, Hameed N, Ashfaq I, Sheikh N (2019) In vivo evaluation of histopathological alterations and trace metals estimation of the small intestine in bisphenol A-intoxicated rats. Can J Gastroenterol Hepatol. https://doi.org/10.1155/2019/9292316

  • Anderson ER, Shah YM (2013) Iron homeostasis in the liver. Compr Physiol 3:315

    Article  Google Scholar 

  • Asghar A, Akhtar T, Batool T, Khawar MB, Nadeem S, Mehmood R, Sheikh N (2021) High-fat diet-induced splenic, hepatic, and skeletal muscle architecture damage: cellular and molecular players. Mol Cell Biochem 476:3671–3679

    Article  CAS  Google Scholar 

  • Brulport A, Le Corre L, Maquart G, Barbet V, Al D, Severin I, Vaiman D, Chagnon MC (2021) Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet. Environ Pollut 270:116243

    Article  CAS  Google Scholar 

  • Cullis JO, Fitzsimons EJ, Griffiths WJ, Tsochatzis E, Thomas DW, British Society for Haematology (2018) Investigation and management of a raised serum ferritin. Br J Haematol 181:331–340

    Article  Google Scholar 

  • ECHA (European Chemicals Agency) (2019) Information on registered substances. Dataset on 4,4′-sulphonyldiphenol (CAS Number 80-09-1), joint submission, first publication 20 Dec 2010, last modification 23 Jul 2019. https://echa.europa.eu/de/registration-dossier/-/ registered-dossier/14986/7/1, accessed 15 Jul 2020

  • Gingrich J, Pu Y, Roberts J, Karthikraj R, Kannan K, Ehrhardt R, Veiga-Lopez A (2018) Gestational bisphenol S impairs placental endocrine function and the fusogenic trophoblast signaling pathway. Arch Toxicol 92:1861–1876

    Article  CAS  Google Scholar 

  • Graham RM, Chua AC, Herbison CE, Olynyk JK, Trinder D (2007) Liver iron transport. World J Gastroenterol 13:4725

    Article  CAS  Google Scholar 

  • Gys C, Kovacic A, Huber C, Lai FY, Heath E, Covaci A (2018) Suspect and untargeted screening of bisphenol S metabolites produced by in vitro human liver metabolism. Toxicol Lett 295:115–123

    Article  CAS  Google Scholar 

  • Helies-Toussaint C, Peyre L, Costanzo C, Chagnon MC, Rahmani R (2014) Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study. Toxicol Appl Pharmacol 280:224–235

    Article  CAS  Google Scholar 

  • Helal EG, Soliman MG, Badawi MM, Abdel-Kawi NA, Fadel HA, Abozaid NM (2018) Physiological and histopathological studies on bisphenol-A compound as xenoestrogen in male albino rats. Egypt J Hosp Med 50:127–136

    Article  Google Scholar 

  • Hussein RM, Eid JI (2013) Pathological mechanisms of liver injury caused by oral administration of bisphenol A. Life Sci J 10:663

    Google Scholar 

  • Immenschuh S, Baumgart-Vogt E, Mueller S (2010) Heme oxygenase-1 and iron in liver inflammation: a complex alliance. Curr Drug Targets 11:1541–1550

    Article  CAS  Google Scholar 

  • Jiang S, Guo T, Guo S, Gao J, Ni Y, Ma W, Zhao R (2021) Chronic variable stress induces hepatic Fe (II) deposition by up-regulating ZIP14 expression via miR-181 family pathway in rats. Biology 10:653

    Article  CAS  Google Scholar 

  • Jung JH, Moon YS, Kim BM, Lee YM, Kim M, Rhee JS (2018) Comparative analysis of distinctive transcriptome profiles with biochemical evidence in bisphenol S-and benzo [a] pyrene-exposed liver tissues of the olive flounder Paralichthys olivaceus. PLoS One 13:e0196425

    Article  Google Scholar 

  • Kazemi S, Mousavi SN, Aghapour F, Rezaee B, Sadeghi F, Moghadamnia AA (2016) Induction effect of bisphenol A on gene expression involving hepatic oxidative stress in rat. Oxidative Med Cell Longev. https://doi.org/10.1155/2016/6298515

  • Kernan KF, Carcillo JA (2017) Hyperferritinemia and inflammation. Int Immunol 29:401–409

    Article  CAS  Google Scholar 

  • Kopitar-Jerala N (2017) The role of interferons in inflammation and inflammasome activation. Front Immunol 8:873

    Article  Google Scholar 

  • Li S, Hong M, Tan HY, Wang N, Feng Y (2016) Insights into the role and interdependence of oxidative stress and inflammation in liver diseases. Oxid Med Cell Longev 2016

  • Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y (2015) The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 16:26087–26124

    Article  CAS  Google Scholar 

  • Li Y, Huang X, Wang J, Huang R, Wan D (2020) Regulation of iron homeostasis and related diseases. Mediat Inflamm 2020

  • Lu L, Zhan T, Ma M, Xu C, Wang J, Zhang C, Liu W, Zhuang S (2018) Thyroid disruption by bisphenol S analogues via thyroid hormone receptor β: in vitro, in vivo, and molecular dynamics simulation study. Environ Sci Technol 52:6617–6625

    Article  CAS  Google Scholar 

  • Mehmood R, Sheikh N, Khawar MB, Abbasi MH, and Mukhtar M (2022) High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver. Mol Biol Rep. 1-10.

  • Pal S, Sarkar K, Nath PP, Mondal M, Khatun A, Paul G (2017) Bisphenol S impairs blood functions and induces cardiovascular risks in rats. Toxicol Rep 4:560–565

    Article  CAS  Google Scholar 

  • Panchanathan R, Liu H, Leung YK, Ho SM, Choubey D (2015) Bisphenol A (BPA) stimulates the interferon signaling and activates the inflammasome activity in myeloid cells. Mol Cell Endocrinol 415:45–55

    Article  CAS  Google Scholar 

  • Peyre L, Rouimi P, de Sousa G, Helies-Toussaint C, Carre B, Barcellini S, Chagnon MC, Rahmani R (2014) Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease. Food Chem Toxicol 70:9–18

    Article  CAS  Google Scholar 

  • Qin J, Ru S, Wang W, Hao L, Ru Y, Wang J, Zhang X (2020) Long-term bisphenol S exposure aggravates non-alcoholic fatty liver by regulating lipid metabolism and inducing endoplasmic reticulum stress response with activation of unfolded protein response in male zebrafish. Environ Pollut:114535

  • Qiu W, Yang M, Liu J, Xu H, Luo S, Wong M, Zheng C (2019) Bisphenol S-induced chronic inflammatory stress in liver via peroxisome proliferator-activated receptor γ using fish in vivo and in vitro models. Environ Pollut 246:963–971

    Article  CAS  Google Scholar 

  • Samardzija D, Pogrmic-Majkic K, Fa S, Stanic B, Jasnic J, Andric N (2018) Bisphenol A decreases progesterone synthesis by disrupting cholesterol homeostasis in rat granulosa cells. Mol Cell Endocrinol 461:55–63

    Article  CAS  Google Scholar 

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108

    Article  CAS  Google Scholar 

  • Skledar DG, Masic LP (2016) Bisphenol A and its analogs: do their metabolites have endocrine activity? Environ Toxicol Pharmacol 47:182–199

    Article  Google Scholar 

  • ul Haq ME, Akash MSH, Rehman K, Mahmood MH (2020) Chronic exposure of bisphenol A impairs carbohydrate and lipid metabolism by altering corresponding enzymatic and metabolic pathways. Environ Toxicol Pharmacol 78:103387

    Article  Google Scholar 

  • Ullah A, Pirzada M, Jahan S, UllahH SG, Rehman H, Siddiqui MF, Butt MA (2018) Bisphenol A and its analogs bisphenol B, bisphenol F, and bisphenol S: comparative in vitro and in vivo studies on the sperms and testicular tissues of rats. Chemosphere 209:508–516

    Article  CAS  Google Scholar 

  • Waidyanatha S, Black SR, Croutch CR, Collins BJ, Silinski MA, Kerns S, Sutherland V, Robinson VG, Aillon K, Fernando RA (2021) Comparative toxicokinetics of bisphenol S and bisphenol AF in male rats and mice following repeated exposure via feed. Xenobiotica 51:210–221

    Article  CAS  Google Scholar 

  • Waidyanatha S, Black SR, Silinski M, Sutherland V, Fletcher BL, Fernando RA, Fennell TR (2020) Comparative toxicokinetics of bisphenol S in rats and mice following gavage administration. Toxicol Appl Pharmacol 406:115207

    Article  CAS  Google Scholar 

  • Waidyanatha S, Black SR, Snyder RW, Yueh YL, Sutherland V, Patel PR, Watson SL, Fennell TR (2018) Disposition and metabolism of the bisphenol analogue, bisphenol S, in Harlan Sprague Dawley rats and B6C3F1/N mice and in vitro in hepatocytes from rats, mice, and humans. Toxicol Appl Pharmacol 351:32–45

    Article  CAS  Google Scholar 

  • Wang CY, Babitt JL (2016) Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol 23:189

    Article  Google Scholar 

  • Wang C, He J, Xu T, Han H, Zhu Z, Meng L, Pang Q, Fan R (2021) Bisphenol A (BPA), BPS and BPB-induced oxidative stress and apoptosis mediated by mitochondria in human neuroblastoma cell lines. Ecotoxicol Environ Saf 207:111299

    Article  CAS  Google Scholar 

  • Wang W, Hafner KS, Flaws JA (2014) In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse. Toxicol Appl Pharmacol 276:157–164

    Article  CAS  Google Scholar 

  • Wang W, Zhang X, Qin J, Wei P, Jia Y, Wang J, Ru S (2019) Long-term bisphenol S exposure induces fat accumulation in liver of adult male zebrafish (Danio rerio) and slows yolk lipid consumption in F1 offspring. Chemosphere 221:500–510

    Article  CAS  Google Scholar 

  • Weiss G (2005) Modification of iron regulation by the inflammatory response. Best Pract Res Clin Haematol 18:183–201

    Article  CAS  Google Scholar 

  • Zhang Z, Lin L, Gai Y, Hong Y, Li L, Weng L (2018) Subchronic bisphenol S exposure affects liver function in mice involving oxidative damage. Regul Toxicol Pharmacol 92:138–144

    Article  CAS  Google Scholar 

  • Zhao C, Tang Z, Yan J, Fang J, Wang H, Cai Z (2017) Bisphenol S exposure modulate macrophage phenotype as defined by cytokines profiling, global metabolomics and lipidomics analysis. Sci Total Environ 592:357–365

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are highly thankful to the Vice-Chancellor, University of the Punjab, Lahore, Pakistan for his support for accomplishing this research work.

Availability of data and materials

All the data used in this research work has been presented. However, any other relevant information regarding the procedures is available on request.

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Authors and Affiliations

  1. Cell & Molecular Biology Lab, Institute of Zoology, University of the Punjab, Q-A-Campus, Lahore, 54590, Pakistan

    Shazia Ghafoor, Tayyaba Saleem & Nadeem Sheikh

  2. Department of Zoology, University of Okara, Okara, Punjab, Pakistan

    Muddasir Hassan Abbasi

  3. Applied Molecular Biology and Biomedicine Lab, Department of Zoology, University of Narowal, Narowal, Pakistan

    Muhammad Babar Khawar

  4. School of Biological Sciences (SBS), University of the Punjab, Q-A-Campus, Lahore, 54590, Pakistan

    Asima Tayyeb & Isbah Ashfaq

Authors
  1. Shazia Ghafoor
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Contributions

Shazia Ghafoor performed the major part of this research work, did statistical analysis, interpretation of results, and initial draft. Muddasir Hassan Abbasi helped in lab work, statistical analysis, and interpretation of results, supervised, and approved the final draft. Muhammad Babar Khawar revised the figures, improved the initial draft, and helped in lab work. Asima Tayyeb, Tayyaba Saleem, and Isbah Ashfaq helped in lab work. Muddasir Hassan Abbasi and Nadeem Sheikh conceived the idea, revised, modified, and approved the final draft.

Corresponding author

Correspondence to Nadeem Sheikh.

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Ethics approval

Animal model preparation and experimental procedures followed in our current study were in full compliance to institutional guidelines approved by Ethical Committee of University of the Punjab, Lahore (2507-ACAD/2020).

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Current research is animal based; therefore, this section does not apply to submitted work.

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The authors declare no competing interests.

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Ghafoor, S., Abbasi, M.H., Khawar, M.B. et al. Bisphenol S induced dysregulations in liver; iron regulatory genes and inflammatory mediators in male Wistar rats. Environ Sci Pollut Res 29, 83711–83722 (2022). https://doi.org/10.1007/s11356-022-21672-2

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