Prominence of Oxidative Stress in the Management of Anti-tuberculosis Drugs Related Hepatotoxicity

Author(s): Preena John, Pravin P. Kale*.

Journal Name: Drug Metabolism Letters

Volume 13 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Advanced medical services and treatments are available for treating Tuberculosis. Related prevalence has increased in recent times. Unfortunately, the continuous consumption of related drugs is also known for inducing hepatotoxicity which is a critical condition and cannot be overlooked. The present review article has focused on the pathways causing these toxicities and also the role of enzyme CYP2E1, hepatic glutathione, Nrf2-ARE signaling pathway, and Membrane Permeability Transition as possible targets which may help in preventing the hepatotoxicity induced by the drugs used in the treatment of tuberculosis.

Keywords: Isoniazid, rifampicin, hepatotoxicity, oxidative stress, anti-tuberculosis drugs, pharmacology.

[1]
Eldehna, W.M.; Fares, M.; Abdel-Aziz, M.M.; Abdel-Aziz, H.A. Design, synthesis and antitubercular activity of certain nicotinic Acid hydrazides. Molecules, 2015, 20(5), 8800-8815.
[http://dx.doi.org/10.3390/molecules20058800] [PMID: 25988611]
[2]
Baskaran, U.L.; Sabina, E.P. Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: A review. J. Integr. Med., 2017, 15(1), 27-36.
[http://dx.doi.org/10.1016/S2095-4964(17)60319-4] [PMID: 28088257]
[3]
Geneva. Global Tuberculosis Report. 2018.https://doi.org/ISBN9789241565394
[4]
Sharifzadeh, M.; Rasoulinejad, M.; Valipour, F.; Nouraie, M.; Vaziri, S. Evaluation of patient-related factors associated with cau-sality, preventability, predictability and severity of hepatotoxicity during antituberclosis treatment. Pharmacol. Res., 2005, 51(4), 353-358.
[http://dx.doi.org/10.1016/j.phrs.2004.10.009] [PMID: 15683749]
[5]
Tostmann, A.; Boeree, M.J.; Aarnoutse, R.E.; de Lange, W.C.M.; van der Ven, A.J.A.M.; Dekhuijzen, R. Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review. J. Gastroenterol. Hepatol., 2008, 23(2), 192-202.
[http://dx.doi.org/10.1111/j.1440-1746.2007.05207.x] [PMID: 17995946]
[6]
Obogwu, M.B.; Akindele, A.J.; Adeyemi, O.O. Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf extract of Mucuna pruriens (Fabaceae) in antitubercular drugs and alcohol models. Chin. J. Nat. Med., 2014, 12(4), 273-283.
[http://dx.doi.org/10.1016/S1875-5364(14)60054-6] [PMID: 24863352]
[7]
Ramappa, V.; Aithal, G.P. Hepatotoxicity related to anti-tuberculosis drugs: Mechanisms and management. J. Clin. Exp. Hepatol., 2013, 3(1), 37-49.
[http://dx.doi.org/10.1016/j.jceh.2012.12.001]
[8]
Steele, M.A.; Burk, R.F.; DesPrez, R.M. Toxic hepatitis with isoni-azid and rifampin. A meta-analysis. Chest, 1991, 99(2), 465-471.
[http://dx.doi.org/10.1378/chest.99.2.465] [PMID: 1824929]
[9]
Teixeira, R.L. de F.; Morato, R.G.; Cabello, P.H.; Muniz, L.M.K. Moreira, Ada.S.; Kritski, A.L.; Mello, F.C.; Suffys, P.N.; Miranda, A.B.; Santos, A.R. Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients. Mem. Inst. Oswaldo Cruz, 2011, 106(6), 716-724.
[http://dx.doi.org/10.1590/S0074-02762011000600011] [PMID: 22012226]
[10]
Lee, K.K.; Fujimoto, K.; Zhang, C.; Schwall, C.T.; Alder, N.N.; Pinkert, C.A.; Krueger, W.; Rasmussen, T.; Boelsterli, U.A. Isoni-azid-induced cell death is precipitated by underlying mitochondrial complex I dysfunction in mouse hepatocytes. Free Radic. Biol. Med., 2013, 65, 584-594.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.038] [PMID: 23911619]
[11]
Boelsterli, U.A.; Lee, K.K. Mechanisms of isoniazid-induced idio-syncratic liver injury: Emerging role of mitochondrial stress. J. Gastroenterol. Hepatol., 2014, 29(4), 678-687.
[http://dx.doi.org/10.1111/jgh.12516] [PMID: 24783247]
[12]
Metushi, I.G.; Sanders, C.; Lee, W.M.; Uetrecht, J.; Uetrecht, J. Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure. Hepatology, 2014, 59(3), 1084-1093.
[http://dx.doi.org/10.1002/hep.26564] [PMID: 23775837]
[13]
Walubo, A.; Smith, P.; Folb, P.I. The role of oxygen free radicals in isoniazid-induced hepatotoxicity. Methods Find. Exp. Clin. Pharmacol., 1998, 20(8), 649-655.
[http://dx.doi.org/10.1358/mf.1998.20.8.487491] [PMID: 9922980]
[14]
Pessayre, D.; Mansouri, A.; Berson, A.; Fromenty, B.Mitochon-drial involvement in drug-induced liver injury; Handbook of ex-perimental pharmacology, 2010, pp. 311-365.
[http://dx.doi.org/10.1007/978-3-642-00663-0_11]
[15]
Fatima, R.; Ashraf, M.; Ejaz, S.; Rasheed, M.A.; Altaf, I.; Afzal, M.; Batool, Z.; Saleem, U.; Anwar, K. In vitro toxic action poten-tial of anti tuberculosis drugs and their combinations. Environ. Toxicol. Pharmacol., 2013, 36(2), 501-513.
[http://dx.doi.org/10.1016/j.etap.2013.05.008] [PMID: 23806997]
[16]
Perwitasari, D.A.; Atthobari, J.; Wilffert, B. Pharmacogenetics of isoniazid-induced hepatotoxicity. Drug Metab. Rev., 2015, 47(2), 222-228.
[http://dx.doi.org/10.3109/03602532.2014.984070] [PMID: 26095714]
[17]
Shaw, P.J.; Ganey, P.E.; Roth, R.A. Idiosyncratic drug-induced liver injury and the role of inflammatory stress with an emphasis on an animal model of trovafloxacin hepatotoxicity. Toxicol. Sci., 2010, 118(1), 7-18.
[http://dx.doi.org/10.1093/toxsci/kfq168] [PMID: 20538741]
[18]
Waring, J.F.; Anderson, M.G. Idiosyncratic toxicity: Mechanistic insights gained from analysis of prior compounds. Curr. Opin. Drug Discov. Devel., 2005, 8(1), 59-65.
[PMID: 15679173]
[19]
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 dis-eases. Int. J. Mol. Sci., 2015, 16(11), 26087-26124.
[http://dx.doi.org/10.3390/ijms161125942] [PMID: 26540040]
[20]
Timperio, A.M.; Rinalducci, S.; Zolla, L. Hydrazide derivatives produce active oxygen species as hydrazine. Bioorg. Chem., 2005, 33(6), 459-469.
[http://dx.doi.org/10.1016/j.bioorg.2005.09.001] [PMID: 16260027]
[21]
Xu, J.J.; Henstock, P.V.; Dunn, M.C.; Smith, A.R.; Chabot, J.R.; de Graaf, D. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol. Sci., 2008, 105(1), 97-105.
[http://dx.doi.org/10.1093/toxsci/kfn109] [PMID: 18524759]
[22]
Rao, ChV.; Rawat, A.K.; Singh, A.P.; Singh, A.; Verma, N. Hepa-toprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models. Asian Pac. J. Trop. Med., 2012, 5(4), 283-288.
[http://dx.doi.org/10.1016/S1995-7645(12)60040-6] [PMID: 22449519]
[23]
Shen, C.; Zhang, G.; Meng, Q. An in vitro model for long-term hepatotoxicity testing utilizing rat hepatocytes entrapped in micro-hollow fiber reactor. Biochem. Eng. J., 2007, 34(3), 267-272.
[http://dx.doi.org/10.1016/j.bej.2006.12.010]
[24]
Chowdhury, A.; Santra, A.; Bhattacharjee, K.; Ghatak, S.; Saha, D.R.; Dhali, G.K. Mitochondrial oxidative stress and permeability transition in isoniazid and rifampicin induced liver injury in mice. J. Hepatol., 2006, 45(1), 117-126.
[http://dx.doi.org/10.1016/j.jhep.2006.01.027] [PMID: 16545483]
[25]
Zhai, Q.; Lu, S-R.; Lin, Y.; Yang, Q-L.; Yu, B. Oxidative stress potentiated by diallylsulfide, a selective CYP2E1 inhibitor, in isoniazid toxic effect on rat primary hepatocytes. Toxicol. Lett., 2008, 183(1-3), 95-98.
[http://dx.doi.org/10.1016/j.toxlet.2008.10.007] [PMID: 18992798]
[26]
Chen, Y.; Xue, P.; Hou, Y.; Zhang, H.; Zheng, H.; Zhou, T.; Qu, W.; Teng, W.; Zhang, Q.; Andersen, M.E.; Pi, J. Isoniazid sup-presses antioxidant response element activities and impairs adipo-genesis in mouse and human preadipocytes. Toxicol. Appl. Pharmacol., 2013, 273(3), 435-441.
[http://dx.doi.org/10.1016/j.taap.2013.10.005] [PMID: 24128855]
[27]
Richards, V.E.; Chau, B.; White, M.R.; Mcqueen, C.A. Hepatic gene expression and lipid homeostasis in C57BL/6 mice exposed to hydrazine or acetylhydrazine. Toxicol. Sci., 2004, 82, 318-332.
[http://dx.doi.org/10.1093/toxsci/kfh232] [PMID: 15282401]
[28]
Saad, E.I.; El-Gowilly, S.M.; Sherhaa, M.O.; Bistawroos, A.E. Role of oxidative stress and nitric oxide in the protective effects of α-lipoic acid and aminoguanidine against isoniazid-rifampicin-induced hepatotoxicity in rats. Food Chem. Toxicol., 2010, 48(7), 1869-1875.
[http://dx.doi.org/10.1016/j.fct.2010.04.026] [PMID: 20417245]
[29]
Pal, R.; Rana, S.V.; Vaiphei, K.; Singh, K. Isoniazid-rifampicin induced lipid changes in rats. Clin. Chim. Acta, 2008, 389(1-2), 55-60.
[http://dx.doi.org/10.1016/j.cca.2007.11.028] [PMID: 18157944]
[30]
Mahmoud, A.M.; Germoush, M.O.; Soliman, A.S. Berberine At-tenuates Isoniazid-Induced Hepatotoxicity by Modulating Perox-isome Proliferator-Activated Receptor? Oxidative Stress and In-flammation. Int. J. Pharmacol., 2014, 10(8), 451-460.
[http://dx.doi.org/10.3923/ijp.2014.451.460]
[31]
Yue, J.; Peng, R. Does CYP2E1 play a major role in the aggrava-tion of isoniazid toxicity by rifampicin in human hepatocytes? Br. J. Pharmacol., 2009, 157(3), 331-333.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00173.x] [PMID: 19371336]
[32]
Caro, A.A.; Cederbaum, A.I.O. Oxidative stress, toxicology, and pharmacology of CYP2E1. Annu. Rev. Pharmacol. Toxicol., 2004, 44(1), 27-42.
[http://dx.doi.org/10.1146/annurev.pharmtox.44.101802.121704] [PMID: 14744237]
[33]
Yew, W.W.; Leung, C.C. Antituberculosis drugs and hepatotoxic-ity. Respirology, 2006, 11(6), 699-707.
[http://dx.doi.org/10.1111/j.1440-1843.2006.00941.x] [PMID: 17052297]
[34]
Adhvaryu, M-R.; Reddy, N.; Parabia, M.H. Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in Guinea pigs. World J. Gastroenterol., 2007, 13(23), 3199-3205.
[http://dx.doi.org/10.3748/wjg.v13.i23.3199] [PMID: 17589898]
[35]
Cheng, J.; Krausz, K.W.; Li, F.; Ma, X.; Gonzalez, F.J. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid. Toxicol. Appl. Pharmacol., 2013, 266(2), 245-253.
[http://dx.doi.org/10.1016/j.taap.2012.10.024] [PMID: 23142471]
[36]
Nanashima, K.; Mawatari, T.; Tahara, N.; Higuchi, N.; Nakaura, A.; Inamine, T.; Kondo, S.; Yanagihara, K.; Fukushima, K.; Suyama, N.; Kohno, S.; Tsukamoto, K. Genetic variants in antioxi-dant pathway: Risk factors for hepatotoxicity in tuberculosis pa-tients. Tuberculosis (Edinb.), 2012, 92(3), 253-259.
[http://dx.doi.org/10.1016/j.tube.2011.12.004] [PMID: 22341855]
[37]
Ingawale, D.K.; Mandlik, S.K.; Naik, S.R. Models of hepatotoxic-ity and the underlying cellular, biochemical and immunological mechanism(s): A critical discussion. Environ. Toxicol. Pharmacol., 2014, 37(1), 118-133.
[http://dx.doi.org/10.1016/j.etap.2013.08.015] [PMID: 24322620]
[38]
Zhang, Z-H.; Tang, J-H.; Zhan, Z-L.; Zhang, X-L.; Wu, H-H.; Hou, Y-N. Cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on QSG-7701 hepatocytes. Asian Pac. J. Trop. Med., 2012, 5(4), 306-309.
[http://dx.doi.org/10.1016/S1995-7645(12)60044-3] [PMID: 22449523]
[39]
Jaswal, A.; Sinha, N.; Bhadauria, M.; Shrivastava, S.; Shukla, S. Therapeutic potential of thymoquinone against anti-tuberculosis drugs induced liver damage. Environ. Toxicol. Pharmacol., 2013, 36(3), 779-786.
[http://dx.doi.org/10.1016/j.etap.2013.07.010] [PMID: 23958970]
[40]
Nakajima, A.; Fukami, T.; Kobayashi, Y.; Watanabe, A.; Naka-jima, M.; Yokoi, T. Human arylacetamide deacetylase is responsi-ble for deacetylation of rifamycins: rifampicin, rifabutin, and rifap-entine. Biochem. Pharmacol., 2011, 82(11), 1747-1756.
[http://dx.doi.org/10.1016/j.bcp.2011.08.003] [PMID: 21856291]
[41]
Acocella, G. Clinical pharmacokinetics of rifampicin. Clin. Pharmacokinet., 1978, 3(2), 108-127.
[http://dx.doi.org/10.2165/00003088-197803020-00002] [PMID: 346286]
[42]
Holdiness, M.R. Clinical pharmacokinetics of the antituberculosis drugs. Clin. Pharmacokinet., 1984, 9(6), 511-544.
[http://dx.doi.org/10.2165/00003088-198409060-00003] [PMID: 6391781]
[43]
Huang, Y.S.; Chern, H-D.; Su, W-J.; Wu, J-C.; Chang, S-C.; Chiang, C-H.; Chang, F-Y.; Lee, S-D. Cytochrome P450 2E1 geno-type and the susceptibility to antituberculosis drug-induced hepati-tis. Hepatology, 2003, 37(4), 924-930.
[http://dx.doi.org/10.1053/jhep.2003.50144] [PMID: 12668988]
[44]
Nannelli, A.; Chirulli, V.; Longo, V.; Gervasi, P.G. Expression and induction by rifampicin of CAR- and PXR-regulated CYP2B and CYP3A in liver, kidney and airways of pig. Toxicology, 2008, 252(1-3), 105-112.
[http://dx.doi.org/10.1016/j.tox.2008.08.004] [PMID: 18786598]
[45]
Burk, O.; Koch, I.; Raucy, J.; Hustert, E.; Eichelbaum, M.; Brock-möller, J.; Zanger, U.M.; Wojnowski, L. The induction of cyto-chrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). J. Biol. Chem., 2004, 279(37), 38379-38385.
[http://dx.doi.org/10.1074/jbc.M404949200] [PMID: 15252010]
[46]
Hassan, H.M.; Guo, H.L.; Yousef, B.A.; Luyong, Z.; Zhenzhou, J. Hepatotoxicity mechanisms of isoniazid: A mini-review. J. Appl. Toxicol., 2015, 35(12), 1427-1432.
[http://dx.doi.org/10.1002/jat.3175] [PMID: 26095833]
[47]
Lian, Y.; Zhao, J.; Wang, Y.M.; Zhao, J.; Peng, S.Q. Metal-lothionein protects against isoniazid-induced liver injury through the inhibition of CYP2E1-dependent oxidative and nitrosative im-pairment in mice. Food Chem. Toxicol., 2017, 102, 32-38.
[http://dx.doi.org/10.1016/j.fct.2017.01.016] [PMID: 28126494]
[48]
Hassan, H.M.; Guo, H.; Yousef, B.A.; Ping-Ping, D.; Zhang, L.; Jiang, Z. Dexamethasone pretreatment alleviates isoni-azid/lipopolysaccharide hepatotoxicity: Inhibition of inflammatory and oxidative stress. Front. Pharmacol., 2017, 8(MAR), 133.
[http://dx.doi.org/10.3389/fphar.2017.00133] [PMID: 28360859]
[49]
Basheer, A.S.; Siddiqui, A.; Paudel, Y.N.; Hassan, M.Q.; Imran, M.; Najmi, A.K.; Akhtar, M. Hepatoprotective and antioxidant ef-fects of fish oil on isoniazid-rifampin induced hepatotoxicity in rats. PharmaNutrition, 2017, 5(1), 29-33.
[http://dx.doi.org/10.1016/j.phanu.2017.01.002]
[50]
Ko, J.W.; Park, S.H.; Shin, N.R.; Shin, J.Y.; Kim, J.W.; Shin, I.S.; Moon, C.; Heo, J.D.; Kim, J.C.; Lee, I.C. Protective effect and mechanism of action of diallyl disulfide against acetaminophen-induced acute hepatotoxicity. Food Chem. Toxicol., 2017, 109(Pt 1), 28-37.
[http://dx.doi.org/10.1016/j.fct.2017.08.029] [PMID: 28847761]
[51]
Khodayar, M.J.; Kalantari, H.; Khorsandi, L.; Rashno, M.; Zei-dooni, L. Betaine protects mice against acetaminophen hepatotox-icity possibly via mitochondrial complex II and glutathione avail-ability. Biomed. Pharmacother., 2018, 103(February), 1436-1445.
[http://dx.doi.org/10.1016/j.biopha.2018.04.154] [PMID: 29864928]
[52]
Lever, M.; Slow, S. The clinical significance of betaine, an osmo-lyte with a key role in methyl group metabolism. Clin. Biochem., 2010, 43(9), 732-744.
[http://dx.doi.org/10.1016/j.clinbiochem.2010.03.009] [PMID: 20346934]
[53]
Kim, S.K.; Kim, Y.C. Attenuation of bacterial lipopolysaccharide-induced hepatotoxicity by betaine or taurine in rats. Food Chem. Toxicol., 2002, 40(4), 545-549.
[http://dx.doi.org/10.1016/S0278-6915(01)00102-8] [PMID: 11893413]
[54]
Bhadauria, S.; Mishra, R.; Kanchan, R.; Tripathi, C.; Srivastava, A.; Tiwari, A.; Sharma, S. Isoniazid-induced apoptosis in HepG2 cells: generation of oxidative stress and Bcl-2 down-regulation. Toxicol. Mech. Methods, 2010, 20(5), 242-251.
[http://dx.doi.org/10.3109/15376511003793325] [PMID: 20433247]
[55]
Masubuchi, Y.; Nakayama, S.; Horie, T. Role of mitochondrial permeability transition in diclofenac-induced hepatocyte injury in rats. Hepatology, 2002, 35(3), 544-551.
[http://dx.doi.org/10.1053/jhep.2002.31871] [PMID: 11870366]
[56]
Ding, W-X.; Shen, H-M.; Ong, C-N. Critical role of reactive oxy-gen species and mitochondrial permeability transition in microcys-tin-induced rapid apoptosis in rat hepatocytes. Hepatology, 2000, 32(3), 547-555.
[http://dx.doi.org/10.1053/jhep.2000.16183] [PMID: 10960448]
[57]
Lemasters, J.J.; Nieminen, A.L.; Qian, T.; Trost, L.C.; Elmore, S.P.; Nishimura, Y.; Crowe, R.A.; Cascio, W.E.; Bradham, C.A.; Brenner, D.A.; Herman, B. The mitochondrial permeability transi-tion in cell death: A common mechanism in necrosis, apoptosis and autophagy. Biochim. Biophys. Acta, 1998, 1366(1-2), 177-196.
[http://dx.doi.org/10.1016/S0005-2728(98)00112-1] [PMID: 9714796]
[58]
Haouzi, D.; Lekéhal, M.; Moreau, A.; Moulis, C.; Feldmann, G.; Robin, M-A.; Lettéron, P.; Fau, D.; Pessayre, D. Cytochrome P450-generated reactive metabolites cause mitochondrial perme-ability transition, caspase activation, and apoptosis in rat hepato-cytes. Hepatology, 2000, 32(2), 303-311.
[http://dx.doi.org/10.1053/jhep.2000.9034] [PMID: 10915737]
[59]
Kaspar, J.W.; Niture, S.K.; Jaiswal, A.K. Nrf2:INrf2 (Keap1) sig-naling in oxidative stress. Free Radic. Biol. Med., 2009, 47(9), 1304-1309.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.07.035] [PMID: 19666107]
[60]
Kensler, T.W.; Wakabayashi, N.; Biswal, S. Cell survival re-sponses to environmental stresses via the Keap1-Nrf2-ARE path-way. Annu. Rev. Pharmacol. Toxicol., 2007, 47(1), 89-116.
[http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141046] [PMID: 16968214]
[61]
Nioi, P.; McMahon, M.; Itoh, K.; Yamamoto, M.; Hayes, J.D. Identification of a novel Nrf2-regulated antioxidant response ele-ment (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: Reassessment of the ARE consensus sequence. Biochem. J., 2003, 374(Pt 2), 337-348.
[http://dx.doi.org/10.1042/bj20030754] [PMID: 12816537]
[62]
Li, W.; Kong, A-N. Molecular mechanisms of Nrf2-mediated anti-oxidant response. Mol. Carcinog., 2009, 48(2), 91-104.
[http://dx.doi.org/10.1002/mc.20465] [PMID: 18618599]
[63]
Motohashi, H.; Yamamoto, M. Nrf2-Keap1 defines a physiologi-cally important stress response mechanism. Trends Mol. Med., 2004, 10(11), 549-557.
[http://dx.doi.org/10.1016/j.molmed.2004.09.003] [PMID: 15519281]
[64]
Cederbaum, A. Nrf2 and antioxidant defense against CYP2E1 toxicity. Expert Opin. Drug Metab. Toxicol., 2009, 5(10), 1223-1244.
[http://dx.doi.org/10.1517/17425250903143769] [PMID: 19671018]
[65]
Gong, P.; Cederbaum, A.I. Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1. Hepatology, 2006, 43(1), 144-153.
[http://dx.doi.org/10.1002/hep.21004] [PMID: 16374848]
[66]
Zhang, Z.; Song, L.; Zhu, L.; Sun, S.; Zheng, G.; Ren, Q.; Xiao, Y.; Feng, F. Mechanisms of Detoxification and anti-oxidation of Nrf2–ARE pathway in isonicotinic acid hydrazide-induced mouse liver injury. J. Health Med. Inform., 2016, 07(02), 1-6.
[http://dx.doi.org/10.4172/2157-7420.1000221]
[67]
Shafik, N.M.; El Batsh, M.M. Protective effects of combined sele-nium and punica granatum treatment on some inflammatory and oxidative stress markers in arsenic-induced hepatotoxicity in rats. Biol. Trace Elem. Res., 2016, 169(1), 121-128.
[http://dx.doi.org/10.1007/s12011-015-0397-1] [PMID: 26085057]
[68]
Li, B.; Wang, L.; Lu, Q.; Da, W. Liver injury attenuation by curcumin in a rat NASH model: An Nrf2 activation-mediated effect? Irish J. Med. Sci.(1971 -), 2016, 185(1), 93-100.
[http://dx.doi.org/10.1007/s11845-014-1226-9]
[69]
Li, S.; Ding, Y.; Niu, Q.; Xu, S.; Pang, L.; Ma, R.; Jing, M.; Feng, G.; Tang, J.X.; Zhang, Q.; Ma, X.; Yan, Y.; Zhang, J.; Wei, M.; Wang, H.X.; Li, F.; Guo, S. Lutein has a protective effect on hepa-totoxicity induced by arsenic via Nrf2 signaling. BioMed Res. Int., 2015.2015315205
[http://dx.doi.org/10.1155/2015/315205] [PMID: 25815309]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 13
ISSUE: 2
Year: 2019
Page: [95 - 101]
Pages: 7
DOI: 10.2174/1872312813666190716155930

Article Metrics

PDF: 16
HTML: 6
PRC: 1