Hepatoprotective Effect of Eulophia gracilis on Benzene-Induced Liver Toxicity in Wistar Rats

Olaniyi Solomon Ola*; Oyeronke Adunni Odunola

**Olaniyi Solomon Ola* and Oyeronke Adunni Odunola**

Volume4-Issue4
Dates: Received: 2023-04-02 | Accepted: 2023-04-06 | Published: 2023-04-10
Pages: 665-677

Abstract

Benzene (BZ) is an organic solvent that can induce pathological disorders such as haematological disburbance and liver damage. Eulophia gracilis (EG) plant is a medicinal orchid explored traditionally to treat myriads of ailments including anemia and liver disease. The present study investigated the protective effect of Eulophia gracilis extract against Benzene-induced hepatotoxicity in haematologically disturbed rats. Male Wistar rats (110-120 g) were randomized into four groups (n = 6 / group): I (control), II BZ-treated: 175 mg/kgbw benzene every alternate days for two weeks; III Co-treated with 175 mg/kgbw benzene and E. gracilis 200 mg/kgbw each day for two weeks and IV administered 200 mg/kg of E. gracilis for two weeks. BZ caused a significant reduction in PCV, Hb, RBC and altered white blood cell count. Similarly, activities of hepatic biomarker enzymes such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase were significantly increased in the BZ-treated group relative to control. Furthermore, BZ caused a significant decrease in the activities of hepatic arylesterase, superoxide dismutase, catalase and glutathione-S-transferase and levels of Ascorbic Acid (AA) and Glutathione (GSH). A significant increase in hepatic malondialdehyde content, altered liver ultrastructure and modulation of p53 and BCl-2 protein in the liver also accompanied benzene intoxication. However, coadministration of E. gracilis ameliorated the BZ-induced changes in haematological parameter and liver biomarkers and improved hepatic antioxidant biomarkers and ultrastructure. Overall, the results suggest that Eulophia gracilis protected against BZ-induced hepatic oxidative damage and haematological disturbance in rats.

FullText HTML FullText PDF DOI: 10.37871/jbres1724

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How to cite this article

Ola OS, Odunola OA. Hepatoprotective Effect of Eulophia gracilis on Benzene-Induced Liver Toxicity in Wistar Rats. J Biomed Res Environ Sci. 2023 Apr 10; 4(4): 665-677. doi: 10.37871/jbres1724, Article ID: JBRES1724, Available at: https://www. jelsciences.com/articles/jbres1724.pdf

Subject area(s)

Biochemistry

References

Sonoda T, Nagata Y, Mori M, Ishida T, Imai K. Meta-analysis of multiple myeloma and benzene exposure. J Epidemiol. 2001 Nov;11(6):249-54. doi: 10.2188/jea.11.249. PMID: 11769942.
Medeiros Vinci R, Jacxsens L, Van Loco J, Matsiko E, Lachat C, de Schaetzen T, Canfyn M, Van Overmeire I, Kolsteren P, De Meulenaer B. Assessment of human exposure to benzene through foods from the Belgian market. Chemosphere. 2012 Aug;88(8):1001-7. doi: 10.1016/j.chemosphere.2012.03.044. Epub 2012 Apr 5. PMID: 22483726.
Benzene - IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. France, Lyon: International Agency for Research on Cancer; 1987. p.1-42.
Snyder R. Leukemia and benzene. Int J Environ Res Public Health. 2012 Aug;9(8):2875-93. doi: 10.3390/ijerph9082875. Epub 2012 Aug 14. PMID: 23066403; PMCID: PMC3447593.
Akanni EO, Folarin OR, Igbeneghu C. Tumour suppressive and organ protective effects of aqueous andrographis paniculata leaves extract on benzene induced leukaemia bearing rats. Annual Research & Review in Biology. 2014;4(7):1070-1079. doi: 10.9734/ARRB/2014/6886.
Sharma M, Porte SM. Role of Ayurveda in management of leukemia (Raktarbuda). IJPSR. 2016;7(2):520-530. doi: 10.13040/IJPSR.0975-8232.7(2).520-30.
Martínez-Velázquez M, Maldonado V, Ortega A, Meléndez-Zajgla J, Albores A. Benzene metabolites induce apoptosis in lymphocytes. Exp Toxicol Pathol. 2006 Aug;58(1):65-70. doi: 10.1016/j.etp.2006.03.010. Epub 2006 May 18. PMID: 16713212.
Snyder R. Leukemia and benzene. Int J Environ Res Public Health. 2012 Aug;9(8):2875-93. doi: 10.3390/ijerph9082875. Epub 2012 Aug 14. PMID: 23066403; PMCID: PMC3447593.
Scandalios JG. Oxidative stress: molecular perception and transduction of signals triggering antioxidant gene defenses. Braz J Med Biol Res. 2005 Jul;38(7):995-1014. doi: 10.1590/s0100-879x2005000700003. Epub 2005 Jul 4. PMID: 16007271.
Hegazy RM, Kamel HFM. Oxidant Hepatic &/or Haem. Injury on fuel-station workers exposed to benzene vapor, possible protection of antioxidants. American Journal of Medicine and Medical Sciences. 2014;4(2):35-46.
Krewski D, Snyder R, Beatty P, Granville G, Meek B, Sonawane B. Assessing the health risks of benzene: A report on the benzene state of the science Workshops. J Toxicol Environ Health. 2000;61:307-38. doi: 10.1080/00984100050166325.
Fernandez-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol Appl Pharmacol. 2005 May 1;204(3):263-73. doi: 10.1016/j.taap.2004.10.001. PMID: 15845418.
Ola OS. Preliminary proximate analysis, chemical composition and phytoconstituents of Eulophia gracilis orchid. International Journal of Sciences: Basic and Applied Research. 2017;36(8):215-222.
National Research Council. Guide for the care and use of laboratory animals. 8th ed. Washington, DC, USA: The National Academies Press; 2011.
Szasz GA. Kinetic photometric method for serum - glutamyl transpeptidase. Clin Chem. 1969;15,124-136.
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957 Jul;28(1):56-63. doi: 10.1093/ajcp/28.1.56. PMID: 13458125.
Tietz NW, Pruden EL, Siggaard-Andersen O. Liver function, in Tietz Textbook of Clinical Chemistry. Burtis AC, Ashwood ER, editors. WB Saunders, London, UK: 1994. p.1354-1374.
Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974;11(3):151-69. doi: 10.1159/000136485. PMID: 4831804.
Jagota SK, Dani HM. A new colorimetric technique for the estimation of vitamin C using Folin phenol reagent. Anal Biochem. 1982 Nov 15;127(1):178-82. doi: 10.1016/0003-2697(82)90162-2. PMID: 7165085.
Varshney R, Kale RK. Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. Int J Radiat Biol. 1990 Nov;58(5):733-43. doi: 10.1080/09553009014552121. PMID: 1977818.
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972 May 25;247(10):3170-5. PMID: 4623845.
Magwere T, Naik YS, Hasler JA. Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney. Free Radic Biol Med. 1997;22(1-2):321-7. doi: 10.1016/s0891-5849(96)00285-7. PMID: 8958157.
Sinha BK. Metabolic activation of procarbazine. Evidence for carbon-centered free-radical intermediates. Biochem Pharmacol. 1984 Sep 1;33(17):2777-81. doi: 10.1016/0006-2952(84)90695-6. PMID: 6431996.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130-9. PMID: 4436300.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973 Feb 9;179(4073):588-90. doi: 10.1126/science.179.4073.588. PMID: 4686466.
Junge W, Klees H. 1,2-Arylesterase. Methods Enzym Anal. 1984;4:8-14.
Uboh FE, Akpanabiatu MI, Eteng MU, Ebong PE, Umoh IB. Toxicological effects of exposure to gasoline vapour in male and female rats. Internet J Toxicol. 2008;4.
Uboh FE, Akpanabiatu MI, Ebong PE, Eyong EU, Eka OU. Evaluation of toxicological implication of inhalation exposure to kerosene and petrol fumes in rats. Acta Biol Szeged. 2005;49:19-22.
Uboh FE, Akpanabiatu MI, Ekaidem IS, Ebong PE, Umoh IB. Effect of inhalation exposure to gasoline fumes on sex hormones profile in Wistar albino rats. Acta Endocrinol. 2007;4:23-30.
Al-Olayan EM, El-Khadragy MF, Aref AM, Othman MS, Kassab RB, Abdel Moneim AE. The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression. Oxid Med Cell Longev. 2014;2014:381413. doi: 10.1155/2014/381413. Epub 2014 Apr 27. PMID: 24876910; PMCID: PMC4020166.
El-Shakour A, El-Ebiarie AS, Ibrahim YH, Abdel Moneim AE, El-Mekawy AM. Effect of benzene on oxidative stress and the functions of liver and kidney in rats. J Environ Occup Sci. 2015;4(1).
Oh JM, Jung YS, Jeon BS, Yoon BI, Lee KS, Kim BH, Oh SJ, Kim SK. Evaluation of hepatotoxicity and oxidative stress in rats treated with tert-butyl hydroperoxide. Food Chem Toxicol. 2012 May;50(5):1215-21. doi: 10.1016/j.fct.2012.01.031. Epub 2012 Feb 1. PMID: 22326806.
Yamamoto T, Kikkawa R, Yamada H, Horii I. Identification of oxidative stress-related proteins for predictive screening of hepatotoxicity using a proteomic approach. J Toxicol Sci. 2005 Aug;30(3):213-27. doi: 10.2131/jts.30.213. PMID: 16141655.
Notas G, Koutroubakis IE, Kouroumalis EA. Oxidants and antioxidants in liver disease, in Antioxidants: New Research. Panglossi HV, editor. 2012. p.2-48.
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002 Jan;82(1):47-95. doi: 10.1152/physrev.00018.2001. PMID: 11773609.
Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol. 2010 Nov;48(11):3246-61. doi: 10.1016/j.fct.2010.08.034. Epub 2010 Sep 4. PMID: 20804811.
Boone L, Meyer D, Cusick P, Ennulat D, Bolliger AP, Everds N, Meador V, Elliott G, Honor D, Bounous D, Jordan H. Selection and interpretation of clinical pathology indicators of hepatic injury in preclinical studies. Vet Clin Pathol. 2005 Sep;34(3):182-8. doi: 10.1111/j.1939-165x.2005.tb00041.x. PMID: 16134065.
Morgenstern R, Zhang J, Johansson K. Microsomal glutathione transferase 1: mechanism and functional roles. Drug Metab Rev. 2011 May;43(2):300-6. doi: 10.3109/03602532.2011.558511. PMID: 21495795.
Sherratt PJ, Hayes JD. Glutathione s-transferases in enzyme systems that metabolise drugs and other xenobiotics. Ioannides C, editor. Chichester: John Wiley & Sons; 2002. p.219-252.
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P. Redox regulation of cell survival. Antioxid Redox Signal. 2008 Aug;10(8):1343-74. doi: 10.1089/ars.2007.1957. PMID: 18522489; PMCID: PMC2932530.
Al-Helaly LA, Ahmed TY. Antioxidants and some biochemical parameters in workers exposed to petroleum station pollutants in mosul city, Iraq. International Research Journal of Environment Sciences. 2014;3(1):31-37.
Chávez J, Cano C, Souki A, Bermúdez V, Medina M, Ciszek A, Amell A, Vargas ME, Reyna N, Toledo A, Cano R, Suárez G, Contreras F, Israili ZH, Hernández-Hernández R, Valasco M. Effect of cigarette smoking on the oxidant/antioxidant balance in healthy subjects. Am J Ther. 2007 Mar-Apr;14(2):189-93. doi: 10.1097/01.psp.0000249918.19016.f6. PMID: 17414589.Chen YY. [Effects of benzene on lipid peroxidation and the activity of relevant enzymes in human]. Zhonghua Yu Fang Yi Xue Za Zhi. 1992 Nov;26(6):336-8. Chinese. PMID: 1303347.Smith MT, Yager JW, Steinmetz KL, Eastmond DA. Peroxidase-dependent metabolism of benzene's phenolic metabolites and its potential role in benzene toxicity and carcinogenicity. Environ Health Perspect. 1989 Jul;82:23-9. doi: 10.1289/ehp.898223. PMID: 2551665; PMCID: PMC1568105.
Bratton SB, Lau SS, Monks TJ. The putative benzene metabolite 2,3, 5-tris(glutathion-S-yl)hydroquinone depletes glutathione, stimulates sphingomyelin turnover, and induces apoptosis in HL-60 cells. Chem Res Toxicol. 2000 Jul;13(7):550-6. doi: 10.1021/tx0000015. PMID: 10898586.Brunmark A, Cadenas E. Reductive addition of glutathione to p-benzoquinone, 2-hydroxy-p-benzoquinone, and p-benzoquinone epoxides. Effect of the hydroxy- and glutathionyl substituents on p-benzohydroquinone autoxidation. Chem Biol Interact. 1988;68(3-4):273-98. doi: 10.1016/0009-2797(88)90021-x. PMID: 3214888..
Emara AM, El-Bahrawy H. Green tea attenuates benzene-induced oxidative stress in pump workers. J Immunotoxicol. 2008 Jan;5(1):69-80. doi: 10.1080/15476910802019029. PMID: 18382860.Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol. 2001 Aug;35(2):297-306. doi: 10.1016/s0168-8278(01)00142-8. PMID: 11580156.Afolabi OK, Wusu AD, Ogunrinola OO, Abam EO, Babayemi DO, Dosumu OA, Onunkwor OB, Balogun EA, Odukoya OO, Ademuyiwa O. Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water. Environ Toxicol. 2016 Feb;31(2):154-62. doi: 10.1002/tox.22030. Epub 2014 Aug 1. PMID: 25082665.
Takaeidi MR, Jahangiri A, Khodayar MJ, Siahpoosh A, Yaghooti H, Rezaei S, Salecheh M, Mansourzadeh Z. The Effect of Date Seed (Phoenix dactylifera) Extract on Paraoxonase and Arylesterase Activities in Hypercholesterolemic Rats. Jundishapur J Nat Pharm Prod. 2014 Feb;9(1):30-4. doi: 10.17795/jjnpp-10368. Epub 2014 Feb 15. PMID: 24644436; PMCID: PMC3957140.
Keskin M, Dolar E, Dirican M, Kiyici M, Yilmaz Y, Gurel S, Nak SG, Erdinc S, Gulten M. Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity. Intern Med J. 2009 Apr;39(4):243-8. doi: 10.1111/j.1445-5994.2009.01793.x. PMID: 19402863.
Rao MN, Marmillot P, Gong M, Palmer DA, Seeff LB, Strader DB, Lakshman MR. Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans. Metabolism. 2003 Oct;52(10):1287-94. doi: 10.1016/s0026-0495(03)00191-4. PMID: 14564680.
Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N Am J Med Sci. 2012 Nov;4(11):523-32. doi: 10.4103/1947-2714.103310. PMID: 23181222; PMCID: PMC3503369.
Kilic SS, Aydin S, Kilic N, Erman F, Aydin S, Celik I. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis. World J Gastroenterol. 2005 Dec 14;11(46):7351-4. doi: 10.3748/wjg.v11.i46.7351. PMID: 16437641; PMCID: PMC4725136.
Zhang C, Peng W, Jiang X, Chen B, Zhu J, Zang Y, Zhang J, Zhu T, Qin J. Transgene expression of human PON1 Q in mice protected the liver against CCl4-induced injury. J Gene Med. 2008 Jan;10(1):94-100. doi: 10.1002/jgm.1128. PMID: 18044792.
Ustundag B, Bahcecioglu IH, Sahin K, Duzgun S, Koca S, Gulcu F, Ozercan IH. Protective effect of soy isoflavones and activity levels of plasma paraoxonase and arylesterase in the experimental nonalcoholic steatohepatitis model. Dig Dis Sci. 2007 Aug;52(8):2006-14. doi: 10.1007/s10620-006-9251-9. Epub 2007 Apr 10. PMID: 17420940.
Ferré N, Camps J, Prats E, Vilella E, Paul A, Figuera L, Joven J. Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage. Clin Chem. 2002 Feb;48(2):261-8. PMID: 11805006.Ferré N, Marsillach J, Camps J, Mackness B, Mackness M, Riu F, Coll B, Tous M, Joven J. Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases. J Hepatol. 2006 Jul;45(1):51-9. doi: 10.1016/j.jhep.2005.12.018. Epub 2006 Feb 6. PMID: 16510204.Marsillach J, Ferré N, Vila MC, Lligoña A, Mackness B, Mackness M, Deulofeu R, Solá R, Parés A, Pedro-Botet J, Joven J, Caballeria J, Camps J. Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease. Clin Biochem. 2007 Jun;40(9-10):645-50. doi: 10.1016/j.clinbiochem.2007.01.020. Epub 2007 Feb 3. PMID: 17335791.Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, Newton RS, La Du B. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999 Apr;26(7-8):892-904. doi: 10.1016/s0891-5849(98)00272-x. PMID: 10232833.
Abu El-Saad AM, Al-Kahtani MA, Abdel-Moneim AM. N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats. Drug Des Devel Ther. 2016 Oct 20;10:3425-3434. doi: 10.2147/DDDT.S115339. PMID: 27799742; PMCID: PMC5076801.
Mehrzadi S, Fatemi I, Malayeri AR, Khodadadi A, Mohammadi F, Mansouri E, Rashno M, Goudarzi M. Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats. Pharmacol Rep. 2018 Aug;70(4):712-719. doi: 10.1016/j.pharep.2018.02.007. Epub 2018 Feb 5. PMID: 29935397.
van Gijssel HE, Maassen CB, Mulder GJ, Meerman JH. p53 protein expression by hepatocarcinogens in the rat liver and its potential role in mitoinhibition of normal hepatocytes as a mechanism of hepatic tumour promotion. Carcinogenesis. 1997 May;18(5):1027-33. doi: 10.1093/carcin/18.5.1027. PMID: 9163691.
Keskin M, Dolar E, Dirican M, Kiyici M, Yilmaz Y, Gurel S, Nak SG, Erdinc S, Gulten M. Baseline and salt-stimulated paraoxonase and arylesterase activities in patients with chronic liver disease: relation to disease severity. Intern Med J. 2009 Apr;39(4):243-8. doi: 10.1111/j.1445-5994.2009.01793.x. PMID: 19402863.
Hess R, Plaumann B, Lutum AS, Haessler C, Heinz B, Fritsche M, Brandner G. Nuclear accumulation of p53 in response to treatment with DNA-damaging agents. Toxicol Lett. 1994 Jun;72(1-3):43-52. doi: 10.1016/0378-4274(94)90008-6. PMID: 8202955.
Milne DM, Campbell DG, Caudwell FB, Meek DW. Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases. J Biol Chem. 1994 Mar 25;269(12):9253-60. PMID: 7510706.Anderson CW. DNA damage and the DNA-activated protein kinase. Trends Biochem Sci. 1993 Nov;18(11):433-7. doi: 10.1016/0968-0004(93)90144-c. PMID: 8291090.
Weaver CV, Liu SP, Lu JF, Lin BS. The effects of benzene exposure on apoptosis in epithelial lung cells: localization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and the immunocytochemical localization of apoptosis-related gene products. Cell Biol Toxicol. 2007 May;23(3):201-20. doi: 10.1007/s10565-006-0165-2. Epub 2006 Dec 14. PMID: 17171516.
Heijne WH, Slitt AL, van Bladeren PJ, Groten JP, Klaassen CD, Stierum RH, van Ommen B. Bromobenzene-induced hepatotoxicity at the transcriptome level. Toxicol Sci. 2004 Jun;79(2):411-22. doi: 10.1093/toxsci/kfh128. Epub 2004 Mar 31. PMID: 15056800.Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000 Mar;21(3):361-70. doi: 10.1093/carcin/21.3.361. PMID: 10688856.
Chen Y, Sun P, Guo X, Gao A. MiR-34a, a promising novel biomarker for benzene toxicity, is involved in cell apoptosis triggered by 1,4-benzoquinone through targeting Bcl-2. Environ Pollut. 2017 Feb;221:256-265. doi: 10.1016/j.envpol.2016.11.072. Epub 2016 Dec 8. PMID: 27939626.Chen Y, Sun P, Bai W, Gao A. MiR-133a regarded as a potential biomarker for benzene toxicity through targeting Caspase-9 to inhibit apoptosis induced by benzene metabolite (1,4-Benzoquinone). Sci Total Environ. 2016 Nov 15;571:883-91. doi: 10.1016/j.scitotenv.2016.07.071. Epub 2016 Jul 15. PMID: 27425441.
Qian S, Han Y, Shi Y, Xu W, Zhu Y, Jiang S, Chen Y, Yu Z, Zhang S, Yang Y, Yu K, Zhang S. Benzene induces haematotoxicity by promoting deacetylation and autophagy. J Cell Mol Med. 2019 Feb;23(2):1022-1033. doi: 10.1111/jcmm.14003. Epub 2018 Nov 8. PMID: 30411500; PMCID: PMC6349156.
Uzma N, Kumar BS, Hazari MA. Exposure to benzene induces oxidative stress, alters the immune response and expression of p53 in gasoline filling workers. Am J Ind Med. 2010 Dec;53(12):1264-70. doi: 10.1002/ajim.20901. PMID: 20886531.
Chen Y, Zhang W, Guo X, Ren J, Gao A. The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity. Cell Death Dis. 2019 Oct 10;10(10):772. doi: 10.1038/s41419-019-2004-4. PMID: 31601785; PMCID: PMC6787223.
Abu El-Saad AM, Al-Kahtani MA, Abdel-Moneim AM. N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats. Drug Des Devel Ther. 2016 Oct 20;10:3425-3434. doi: 10.2147/DDDT.S115339. PMID: 27799742; PMCID: PMC5076801.
Mehrzadi S, Fatemi I, Malayeri AR, Khodadadi A, Mohammadi F, Mansouri E, Rashno M, Goudarzi M. Ellagic acid mitigates sodium arsenite-induced renal and hepatic toxicity in male Wistar rats. Pharmacol Rep. 2018 Aug;70(4):712-719. doi: 10.1016/j.pharep.2018.02.007. Epub 2018 Feb 5. PMID: 29935397.
van Gijssel HE, Maassen CB, Mulder GJ, Meerman JH. p53 protein expression by hepatocarcinogens in the rat liver and its potential role in mitoinhibition of normal hepatocytes as a mechanism of hepatic tumour promotion. Carcinogenesis. 1997 May;18(5):1027-33. doi: 10.1093/carcin/18.5.1027. PMID: 9163691.
Rämet M, Castrén K, Järvinen K, Pekkala K, Turpeenniemi-Hujanen T, Soini Y, Pääkkö P, Vähäkangas K. p53 protein expression is correlated with benzo[a]pyrene-DNA adducts in carcinoma cell lines. Carcinogenesis. 1995 Sep;16(9):2117-24. doi: 10.1093/carcin/16.9.2117. PMID: 7554063.
Hess R, Plaumann B, Lutum AS, Haessler C, Heinz B, Fritsche M, Brandner G. Nuclear accumulation of p53 in response to treatment with DNA-damaging agents. Toxicol Lett. 1994 Jun;72(1-3):43-52. doi: 10.1016/0378-4274(94)90008-6. PMID: 8202955.
Milne DM, Campbell DG, Caudwell FB, Meek DW. Phosphorylation of the tumor suppressor protein p53 by mitogen-activated protein kinases. J Biol Chem. 1994 Mar 25;269(12):9253-60. PMID: 7510706.
Anderson CW. DNA damage and the DNA-activated protein kinase. Trends Biochem Sci. 1993 Nov;18(11):433-7. doi: 10.1016/0968-0004(93)90144-c. PMID: 8291090.
Weaver CV, Liu SP, Lu JF, Lin BS. The effects of benzene exposure on apoptosis in epithelial lung cells: localization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and the immunocytochemical localization of apoptosis-related gene products. Cell Biol Toxicol. 2007 May;23(3):201-20. doi: 10.1007/s10565-006-0165-2. Epub 2006 Dec 14. PMID: 17171516.
Heijne WH, Slitt AL, van Bladeren PJ, Groten JP, Klaassen CD, Stierum RH, van Ommen B. Bromobenzene-induced hepatotoxicity at the transcriptome level. Toxicol Sci. 2004 Jun;79(2):411-22. doi: 10.1093/toxsci/kfh128. Epub 2004 Mar 31. PMID: 15056800.
Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis. 2000 Mar;21(3):361-70. doi: 10.1093/carcin/21.3.361. PMID: 10688856.
Chen Y, Sun P, Guo X, Gao A. MiR-34a, a promising novel biomarker for benzene toxicity, is involved in cell apoptosis triggered by 1,4-benzoquinone through targeting Bcl-2. Environ Pollut. 2017 Feb;221:256-265. doi: 10.1016/j.envpol.2016.11.072. Epub 2016 Dec 8. PMID: 27939626.
Chen Y, Sun P, Bai W, Gao A. MiR-133a regarded as a potential biomarker for benzene toxicity through targeting Caspase-9 to inhibit apoptosis induced by benzene metabolite (1,4-Benzoquinone). Sci Total Environ. 2016 Nov 15;571:883-91. doi: 10.1016/j.scitotenv.2016.07.071. Epub 2016 Jul 15. PMID: 27425441.
Qian S, Han Y, Shi Y, Xu W, Zhu Y, Jiang S, Chen Y, Yu Z, Zhang S, Yang Y, Yu K, Zhang S. Benzene induces haematotoxicity by promoting deacetylation and autophagy. J Cell Mol Med. 2019 Feb;23(2):1022-1033. doi: 10.1111/jcmm.14003. Epub 2018 Nov 8. PMID: 30411500; PMCID: PMC6349156.
Uzma N, Kumar BS, Hazari MA. Exposure to benzene induces oxidative stress, alters the immune response and expression of p53 in gasoline filling workers. Am J Ind Med. 2010 Dec;53(12):1264-70. doi: 10.1002/ajim.20901. PMID: 20886531.
Chen Y, Zhang W, Guo X, Ren J, Gao A. The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity. Cell Death Dis. 2019 Oct 10;10(10):772. doi: 10.1038/s41419-019-2004-4. PMID: 31601785; PMCID: PMC6787223.
Kuo ML, Shiah SG, Wang CJ, Chuang SE. Suppression of apoptosis by Bcl-2 to enhance benzene metabolites-induced oxidative DNA damage and mutagenesis: A possible mechanism of carcinogenesis. Mol Pharmacol. 1999 May;55(5):894-901. PMID: 10220568.