Hazards of Chronic Exposure to Nonylphenol: Concomitant Effect on Non-alcoholic Fatty Liver Disease in Male Albino Rats

Rania Elsyade; Eman El Sawaf; Dalia Gaber

doi:10.3889/oamjms.2021.6237

Authors

Rania Elsyade Department of Anatomy and Embryology, Faculty of Medicine, Helwan University, Cairo, Egypt https://orcid.org/0000-0002-8597-9515
Eman El Sawaf Department of Anatomy and Embryology, Faculty of Medicine, Helwan University, Cairo, Egypt https://orcid.org/0000-0003-3501-2661
Dalia Gaber Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Helwan University, Cairo, Egypt https://orcid.org/0000-0003-2676-9152

DOI:

https://doi.org/10.3889/oamjms.2021.6237

Keywords:

Non-alcoholic steatohepatitis, Nonylphenol, Oxidative stress, Heme oxygenase-1, Apoptosis

Abstract

BACKGROUND: Chronic exposure to environmental endocrine disruptors like nonylphenol (NP), has been shown in previous studies to predispose to non-alcoholic fatty liver disease.

METHODS: In this work, forty adult male albino rats were divided into four groups, a high sucrose-high-fat diet (HSHFD) group, a group receiving 20 μg/kg/day of NP, an NP + HSHFD group, and a control group. The rats were sacrificed on day 60 after anesthetization.

RESULTS: Biochemical tests indicated that serum transaminases (alanine aminotransferase, aspartate aminotransferase) were significantly increased in the NP + HSHFD group. Lipid metabolism was most disrupted in the NP + HSHFD with a highly significant increase (p < 0.001) of serum cholesterol, triglyceride, and low-density lipoprotein cholesterol compared to other groups. Heme oxygenase 1 showed the highest expression in the NP + HSHFD group, with a highly significant difference in comparison with the other groups (p < 0.001). Histopathological studies revealed fatty changes and dilatation in the central vein in the HSHFD group. Lymphoid cell aggregates were detected in the NP group. Massive inflammation and degeneration were revealed in the NP + HSHFD group. There was also marked expression of the apoptotic protein caspase-3 in the NP + HSHFD group.

CONCLUSION: In conclusion, exposure to a 20 μg/kg/day of NP induced oxidative stress leading to non-alcoholic steatohepatitis.

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References

Ramzan M, Ali I, Matin A. Sonographic assessment of hepatic steatosis (fatty liver) in school children of Dera Ismail Khan city (NWF P) Pakistan. Pak J Nutr. 2009;8(6):797-9. https://doi.org/10.3923/pjn.2009.797.799 DOI: https://doi.org/10.3923/pjn.2009.797.799

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. https://doi.org/10.1002/hep.28431 PMid:26707365 DOI: https://doi.org/10.1002/hep.28431

Marchesini G, Day CP, Dufour JF, Canbay A, Nobili V, Ratziu V, et al. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402. https://doi.org/10.1016/j.jhep.2015.11.004 PMid:27062661 DOI: https://doi.org/10.1016/j.jhep.2015.11.004

Machado MV, Cortez-Pinto H. Non-alcoholic fatty liver disease: What the clinician needs to know. World J Gastroenterol. 2014;20(36):12956-80. https://doi.org/10.3748/wjg.v20.i36.12956 PMid:25278691 DOI: https://doi.org/10.3748/wjg.v20.i36.12956

Yan HM, Gao X, Liu M. Study of the association between non-alcoholic fatty liver disease and metabolic syndrome. Chin J Diabet. 2006;14:326-8.

Jie Y, Pan W, Wenxia Y, Feng G, Liting H, Wenmei L, et al. The effects of gestational and lactational exposure to Nonylphenol on c-Jun, c-fos and learning and memory in hippocampus in male F1 rat. Iran J Basic Med Sci. 2017;20(4):386-91. PMid:29026496

Jie Y, Xuefeng Y, Mengxue Y, Xuesong Y, Jing Y, Yin T, et al. Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity. Wien Klin Wochenschr. 2016;128(11-12):426-34. https://doi.org/10.1007/s00508-016-0960-6 PMid:26905877 DOI: https://doi.org/10.1007/s00508-016-0960-6

Verner MA, Magher T, Haddad S. High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol a and nonylphenol in rats. Xenobiotica. 2010;40(2):83-92. https://doi.org/10.3109/00498250903383334 PMid:19916736 DOI: https://doi.org/10.3109/00498250903383334

Kazemi S, Feizi F, Aghapour F, Joorsaraee GA, Moghadamnia AA. Histopathology and histomorphometric investigation of bisphenol a and nonylphenol on the male rat reproductive system. N Am J Med Sci. 2016;8(5):215-21. https://doi.org/10.4103/1947-2714.183012 PMid:27298816 DOI: https://doi.org/10.4103/1947-2714.183012

Jie X, Yang W, Jie Y, Fan QY, Liu XY, Yan L, et al. Immune effects of nonylphenol on offspring of rats exposed during pregnancy. Hum Ecol Risk Assess. 2010;16(2):444-52. https://doi.org/10.1080/10807031003670485 DOI: https://doi.org/10.1080/10807031003670485

Couderc M, Gandar A, Kamari A, Allain Y, Zalouk-Vergnoux A, Herrenknecht C, et al. Neurodevelopmental and behavioral effects of nonylphenol exposure during gestational and breastfeeding period on F1 rats. Neurotoxicology. 2014;44:237-49. https://doi.org/10.1016/j.neuro.2014.07.002 PMid:25058900 DOI: https://doi.org/10.1016/j.neuro.2014.07.002

Lee HA, Park SH, Hong YS, Ha EH, Park H. The effect of exposure to persistent organic pollutants on metabolic health among KOREAN children during a 1-year follow-up. Int J Environ Res Public Health. 2016;13(3):E270. https://doi.org/10.3390/ijerph13030270 PMid:26938545 DOI: https://doi.org/10.3390/ijerph13030270

Kourouma A, Keita H, Duan P, Quan C, Bilivogui KK, Qi S, et al. Effects of 4-nonylphenol on oxidant/antioxidant balance system inducing hepatic steatosis in male rat. Toxicol Rep. 2015;2:1423-33. https://doi.org/10.1016/j.toxrep.2015.10.006 PMid:28962484 DOI: https://doi.org/10.1016/j.toxrep.2015.10.006

Tran V, Tindula G, Huen K, Bradman A, Harley K, Kogut K, et al. Prenatal phthalate exposure and 8-isoprostane among Mexican- American children with high prevalence of obesity. J Dev Orig Health Dis. 2017;8(2):196-205. https://doi.org/10.1017/s2040174416000763 PMid:28031075 DOI: https://doi.org/10.1017/S2040174416000763

Geng S, Wang S, Zhu W, Xie C, Li X, Wu J, et al. Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways. Toxicol Lett. 2017;272:75-83. https://doi.org/10.1016/j.toxlet.2017.03.011 PMid:28300666 DOI: https://doi.org/10.1016/j.toxlet.2017.03.011

Saponaro C, Gaggini M, Gastaldelli A. Nonalcoholic fatty liver disease and Type 2 diabetes: Common pathophysiologic mechanisms. Curr Diab Rep. 2015;15(6):607. https://doi.org/10.1007/s11892-015-0607-4 PMid:25894944 DOI: https://doi.org/10.1007/s11892-015-0607-4

Korkmaz A, Ahbab MA, Kolankaya D, Barlas N. Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food Chem Toxicol. 2010;48(10):2865e-71. https://doi.org/10.1016/j.fct.2010.07.019 PMid:20643179 DOI: https://doi.org/10.1016/j.fct.2010.07.019

Daidoji T, Inoue H, Kato S, Yokota H. Glucuronidation and excretion of nonylphenol in perfused rat liver. Drug Metab Dispos. 2003;31(8):993e-8. https://doi.org/10.1124/dmd.31.8.993 PMid:12867487 DOI: https://doi.org/10.1124/dmd.31.8.993

Jubendradass R, D’Cruz SC, Mathur PP. Short-term exposure to nonylphenol induces pancreatic oxidative stress and alters liver glucose metabolism in adult female rats. J Biochem Mol Toxicol. 2011;25(2):77e-83. https://doi.org/10.1002/jbt.20361 PMid:21472897 DOI: https://doi.org/10.1002/jbt.20361

Yu J, Yang X, Luo Y, Yang X, Yang M, Yang J, et al. Adverse effects of chronic exposure to nonylphenol on nonalcoholic fatty liver disease in male rats. PLoS One. 2017;12(7):e0180218. https://doi.org/10.1371/journal.pone.0180218 PMid:28686624 DOI: https://doi.org/10.1371/journal.pone.0180218

Yu J, Yang X, Yang X, Yang M, Wang P, Yang Y, et al. Nonylphenol aggravates nonalcoholic fatty liver disease in high sucrose-high fat diet-treated rat. Sci Rep. 2018;8:3232. https://doi.org/10.1038/s41598-018-21725-y DOI: https://doi.org/10.1038/s41598-018-21725-y

Bancroft JD, Stevens A. Theory and Practice of Histological Techniques. 4th ed. New York: Churchill Livingstone; 1996.

Mohamed AK, Magdy M. Caspase 3 role and immunohistochemical expression in assessment of apoptosis as a feature of H1N1 vaccine-caused Drug-Induced Liver Injury (DILI). Electronic Physician. 2017;9(5):4261-73. https://doi.org/10.19082/4261 PMid:28713494 DOI: https://doi.org/10.19082/4261

Snedecor GM, Cochran WG. Statistical Methods. 7th ed. Ames: Iowa State Univ Press; 1980. p. 325-330.

Härdle W, Simar L. Applied Multivariate Statistical Analysis. 2nd ed. Berlin, Germany: Springer. 2007. p. 420.

Lin X, Ni Y, Kokot S. An electrochemical DNA-sensor developed with the use of methylene blue as a redox indicator for the detection of DNA damage induced by endocrine-disrupting compounds. Anal Chim Acta. 2015;867:29-37. https://doi. org/10.1016/j.aca.2015.02.050 PMid:25813025 DOI: https://doi.org/10.1016/j.aca.2015.02.050

Ben-Jonathan N, Steinmetz R. Xenoestrogens: The emerging story of bisphenol a. Trends Endocrinol Metab 1998;9(3):124e-8. https://doi.org/10.1016/s1043-2760(98)00029-0 PMid:18406253 DOI: https://doi.org/10.1016/S1043-2760(98)00029-0

Kazemi S, Kani SN, Ghasemi-Kasman M, Aghapour F, Khorasani H, Moghadamnia AA. Nonylphenol induces liver toxicity and oxidative stress in rat. Biochem Biophys Res Commun. 2016;479(1):17e-21. https://doi.org/10.1016/j.bbrc.2016.08.164 PMid:27590577 DOI: https://doi.org/10.1016/j.bbrc.2016.08.164

Pari L, Amali DR. Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats. J Pharm. 2005;8(1):115-23. PMid:15946605

Jubendradass R, D’Cruz SC, Rani SA, Mathur PP. Nonylphenol induces apoptosis via mitochondria-and Fas mediated pathways in the liver of adult male rat. Regul Toxicol Pharmacol. 2012;62(3):405-11. https://doi.org/10.1016/j.yrtph.2012.01.004 DOI: https://doi.org/10.1016/j.yrtph.2012.01.004

Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, et al. In vivo effects of bisphenol a in laboratory rodent studies. Reprod Toxicol. 2007;24(2):199-224. https://doi.org/10.1016/j.reprotox.2007.06.004 PMid:17683900 DOI: https://doi.org/10.1016/j.reprotox.2007.06.004

Sepulveda J. Challenges in routine clinical chemistry analysis: Proteins and enzymes. In: Accurate Results in the Clinical Laboratory. A Guide to Error Detection and Correction. Netherlands: Elsevier; 2013. p. 131-48. https://doi.org/10.1016/b978-0-12-415783-5.00009-8 DOI: https://doi.org/10.1016/B978-0-12-415783-5.00009-8

Noorimotlagh Z, Mirzaee SA, Ahmadi M, Jaafarzadeh N, Rahimd F. The possible DNA damage induced by environmental organic compounds: The case of Nonylphenol. Ecotoxicol Environ Saf. 2018;158:171-81. https://doi.org/10.1016/j.ecoenv.2018.04.023 PMid:29684747 DOI: https://doi.org/10.1016/j.ecoenv.2018.04.023

Lia R, Zhaoa L, Zhanga L, Chena M, Donga C, Caib Z. DNA damage and repair, oxidative stress and metabolism biomarker responses in lungs of rats exposed to ambient atmospheric 1-nitropyrene. Environ Toxicol Pharmacol. 2017;54:14-20. https://doi.org/10.1016/j.etap.2017.06.009 Mid:28668703 DOI: https://doi.org/10.1016/j.etap.2017.06.009