Nuclear Factor Erythroid-2 Linked Factor (Nrf2) as a Potential Mediator of Hepatotoxicity

Authors

  • Inam Sameh Arif Department of Pharmacology and Toxicology
  • Israa Burhan Raoof Department of Clinical Laboratory Science, College of Pharmacy, Mustansiriyah University, Baghdad- Iraq.
  • Hayder Hussein Luaibi Department of Clinical Laboratory Science, College of Pharmacy, Mustansiriyah University, Baghdad- Iraq

DOI:

https://doi.org/10.32947/ajps.v21i4.796

Abstract

Hepatotoxicity is a term used to describe serious health complications of liver disease caused by a variety of factors. Nuclear factor erythroid-2 linked factor (Nrf2) as a potential mediator of hepatotoxicity via inflammatory and induction of oxidative stress, oxidation

produces more toxic compounds caused more pathogenic cases; therefore, to maintain sufficient homeostasis, involve antioxidant materials and detoxification factors. Controlling cytokine activity in normal cells is a useful way to regulate the signaling pathway of Nrf2. Recent studies found a relation between each Nrf2 and NF-κB activation and drug-induced liver injury.  This review presents a detailed and conformation update of Nrf2 roles in hepatotoxicity which considers that drug-induced liver injury is the main problem to draw attention in medical clinics and to develop new drugs with less harmful to the liver. In addition to that. Kept each of normal oxidation and cytokines levels is crucial responses for cells alteration and remaining to survive.

References

- Krajka-Kuźniak V. Paluszczak J. Baer-Dubowska W. The Nrf2-ARE signaling pathway: An update on its regulation and possible role in cancer prevention and treatment. Pharmacol. Rep. 2017; 69: 393–402.

- Hayes, J.D. McMahon. M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 2009; 34: 176–188.

- Jie L. Kai Connie W. Yuan-Fu L. et al. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants. Oxidative Medicine and Cellular Longevity.2013; 2013:1-8.

- Tang, W. Jiang, Y.F. Ponnusamy, M.; Diallo, M. Role of Nrf2 in chronic liver disease. World J. Gastroenterol. 2014; 20: 13079–13087

- Xu, D. Xu, M. Jeong, S. Qian, Y. Wu, H. Xia, Q. Kong X. The role of Nrf2 in liver disease: Novel molecular mechanisms and therapeutic approaches. Front. Pharmacol. 2019; 9:1428.

- Galicia-Moreno. M. Gutierrez-Reyes G. The role of oxidative stress in the development of alcoholic liver disease. Rev. Gastroenterol. México. 2014; 79:135–144.

- Ramos-Tovar E. Muriel P. Free radicals, antioxidants, nuclear factor -E2-related factor-2 and liver damage. J. Appl. Toxicol. 2020;40: 151–168.

- Bram Herpers, Steven Wink, Lisa Fredriksson . Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity. Archives of Toxicology volume. 3016; 90:1163–1179.

- Li S. Tan, H.Y. Wang, N. Zhang, Z.J. Lao L. Wong, C.W. Feng Y. The role of oxidative stress and antioxidants in liver diseases. Int. J. Mol. Sci. 2015; 16: 26087–26124.

- Inam S. Yassir M. Israa B. Nrf2 as a modulator of oxidative stress. Al Mustansiriyah Journal of Pharmaceutical Sciences, 2019;21(3):25-32.

- Abdul Muhaimen A. Monther F. Ayad k. Design, Synthesis, and Acute Anti-inflammatory Assessment of New 2- methyl Benzoimidazole Derivatives Having 4-Thiazolidinone Nucleus. Al Mustansiriyah Journal of Pharmaceutical Sciences, 2019;19(4):151-160.

- Dongwei X. Min X. and Seogsong J. The Role of Nrf2 in Liver Disease: Novel Molecular Mechanisms and Therapeutic Approaches. Frontiers in Pharmacology. 2019; 9: 1428.

- Chan K. Han XD. Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc. Natl. Acad. Sci. The USA. 2001; 98:4611–16.

- Zhou R. Tardivel A. Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat. Immunol. 2010; 11:136–40.

- Moi P. Chan K. Asunis I. Cao A. Kan YW. Isolation of NF-E2-related factor 2 (NRF2), an NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences of the United States of America. 1994;91 (21): 9926 30.

- Zhou J. Zhang X. Tang H. Yu J. Zu X. Xie, Z.Yang, X. Hu, J. Tan, F. Li Q. et al. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) in autophagy-induced hepatocellular carcinoma. Clin. Chim. Acta. 2020; 506; 1–8.

- Xu, D. Xu M. Jeong S. Qian Y.Wu H.; Xia Q. Kong X. The role of Nrf2 in liver disease: Novel molecular mechanisms and therapeutic approaches. Front. Pharmacol. 2019; 9: 1428.

- DeNicola GM. KaGarethA. Humpton TJ. Gopinathan A. Wei C. Frese K. et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011; 475 (7354): 106–9.

- Barajas B. Che N. Yin F. Rowshanrad A. Orozco LD. Gong KW. et al. NF-E2- related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011; 31 (1): 58–66.

- Marina G. Silvia Lucano L. Hugo Christian Monroy R. Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects. Antioxidants 2020; 9 (980):1-23.

- Robledinos-Anton N. Fernandez-Gines R. Manda G. Cuadrado, A. Activators and inhibitors of Nrf2: A review of their potential for clinical development. Oxid. Med. Cell. Longev. 2019;14: 9372182.

- Kaibori M, Yanagida H, Yokogawa N, Hijikawa T, Kwon AH, Okumura T, Kamiyama Y. Effects of pirfenidone on endotoxin-induced liver injury after partial hepatectomy in rats. InTransplantation proceedings 2004 Sep 1 (Vol. 36, No. 7, pp. 1975-1976). Elsevier.

- Hamadi N, Mansour A, Hassan MH, Khalifa‐Touhami F, Bacary O. Ameliorative effects of resveratrol on liver injury in streptozotocin‐induced diabetic rats. Journal of biochemical and molecular toxicology. 2012 Oct;26(10):384-92.

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Published

2022-04-19