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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

General Research Article

Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp

Author(s): Bao Sun, Yue Yang, Mengzi He, Yanan Jin, Xiaoyu Cao, Xiwei Du and Ruixia Yang*

Volume 21, Issue 7, 2020

Page: [541 - 547] Pages: 7

DOI: 10.2174/1389200221666200620203648

Price: $65

Abstract

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue.

Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion.

Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained.

Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels.

Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.

Keywords: Chemotherapeutic agents, doxocubicin, berberine, Cyp, TLRs, inflammation.

Graphical Abstract

[1]
Guengerich, F.P. Oxidative cleavage of carboxylic esters by cytochrome P-450. J. Biol. Chem., 1987, 262(18), 8459-8462.
[PMID: 3597381]
[2]
Young, R.C.; Ozols, R.F.; Myers, C.E. The anthracycline antineoplastic drugs. N. Engl. J. Med., 1981, 305(3), 139-153.
[http://dx.doi.org/10.1056/NEJM198107163050305 ] [PMID: 7017406]
[3]
Weiss, R.B. The anthracyclines: will we ever find a better doxorubicin? Semin. Oncol., 1992, 19(6), 670-686.
[PMID: 1462166]
[4]
Cusack, B.J.; Young, S.P.; Olson, R.D. Daunorubicin and daunorubicinol pharmacokinetics in plasma and tissues in the rat. Cancer Chemother. Pharmacol., 1995, 35(3), 213-218.
[http://dx.doi.org/10.1007/BF00686550 ] [PMID: 7805179]
[5]
Yeh, E.T.H.; Tong, A.T.; Lenihan, D.J.; Yusuf, S.W.; Swafford, J.; Champion, C.; Durand, J.B.; Gibbs, H.; Zafarmand, A.A.; Ewer, M.S. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 2004, 109(25), 3122-3131.
[http://dx.doi.org/10.1161/01.CIR.0000133187.74800.B9 ] [PMID: 15226229]
[6]
Kalender, Y.; Yel, M.; Kalender, S. Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin. Toxicology, 2005, 209(1), 39-45.
[http://dx.doi.org/10.1016/j.tox.2004.12.003 ] [PMID: 15725512]
[7]
Bárdi, E.; Bobok, I.V.; Oláh, A.; Kappelmayer, J.; Kiss, C. Anthracycline antibiotics induce acute renal tubular toxicity in children with cancer. Pathol. Oncol. Res., 2007, 13(3), 249-253.
[http://dx.doi.org/10.1007/BF02893506 ] [PMID: 17922055]
[8]
Zordoky, B.N.M.; El-Kadi, A.O.S. Induction of several cytochrome P450 genes by doxorubicin in H9c2 cells. Vascul. Pharmacol., 2008, 49(4-6), 166-172.
[http://dx.doi.org/10.1016/j.vph.2008.07.004 ] [PMID: 18707023]
[9]
Liu, H.X.; Li, J.; Li, Q.X. Therapeutic effect of valsartan against doxorubicin-induced renal toxicity in rats. Iran. J. Basic Med. Sci., 2019, 22(3), 251-254.
[PMID: 31156784]
[10]
Venkova, L.S.; Zerkalenkova, E.A.; Minin, A.A. Vimentin protects cells against doxorubicin and vincristine. biochem. Supple Series A: Membrane Cell Biol., 2018, 12(3), 255-260.
[11]
Rizvi, T.F.; Razauddin, M.; Urrahman, M.S.; Jahan, T.; Naz, Z.; Kumar, R.; Kumar, A.; Ali, M. Immunomodulatory effect of ashwagandha against doxorubicin toxicity. Eur. J. Pharm. Med. Res., 2016, 3(7), 463-467.
[12]
Li, Z.; Geng, Y.N.; Jiang, J.D.; Kong, W.J. Antioxidant and antiinflammatory activities of berberine in the treatment of diabetes mellitus. eCAM., 2014, 2014, 289264-289276.
[13]
Zhao, X.; Zhang, J.; Tong, N.; Chen, Y.; Luo, Y. Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biol. Pharm. Bull., 2012, 35(5), 796-800.
[http://dx.doi.org/10.1248/bpb.35.796 ] [PMID: 22687420]
[14]
Habig, W.H.; Pabst, M.J.; Jakoby, W.B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol. Chem., 1974, 249(22), 7130-7139.
[PMID: 4436300]
[15]
Beers, R.F., Jr; Sizer, I.W. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem., 1952, 195(1), 133-140.
[PMID: 14938361]
[16]
Misra, H.P.; Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem., 1972, 247(10), 3170-3175.
[PMID: 4623845]
[17]
Rayan, D.; Lu, A.; Levin, W. Preparation of rat hepatic microsomes. Methods Enzymol., 1978, 752, 118-122.
[18]
Richardson, S.J.; Bai, A.; Kulkarni, A.A.; Moghaddam, M.F. Efficiency in drug discovery: liver S9 fraction assay as a screen for metabolic stability. Drug Metab. Lett., 2016, 10(2), 83-90.
[http://dx.doi.org/10.2174/1872312810666160223121836 ] [PMID: 26902079]
[19]
Williams, C.H., Jr; Kamin, H. Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver. J. Biol. Chem., 1962, 237, 587-595.
[PMID: 14007123]
[20]
Chiu, D.T.; Stults, F.H.; Tappel, A.L. Purification and properties of rat lung soluble glutathione peroxidase. Biochim. Biophys. Acta, 1976, 445(3), 558-566.
[http://dx.doi.org/10.1016/0005-2744(76)90110-8 ] [PMID: 974099]
[21]
Tappel, A.L.; Zalkin, H. Inhibition of lipid peroxidation in mitochondria by vitamin E. Arch. Biochem. Biophys., 1959, 80, 333-336.
[http://dx.doi.org/10.1016/0003-9861(59)90259-0]
[22]
Mitchell, J.R.; Jollow, D.J.; Potter, W.Z.; Davis, D.C.; Gillette, J.R.; Brodie, B.B. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmacol. Exp. Ther., 1973, 187(1), 185-194.
[PMID: 4746326]
[23]
Drury, A.A.; Wallington, E.A. Carleton’s histological technique, 5th ed; Oxford University Press: New York, Toronto, 1980.
[24]
Zhou, S.F.; Xue, C.C.; Yu, X.Q.; Wang, G. Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update. Curr. Drug Metab., 2007, 8(6), 526-553.
[http://dx.doi.org/10.2174/138920007781368863 ] [PMID: 17691916]
[25]
Pradeep, K.; Mohan, C.V.; Gobianand, K.; Karthikeyan, S. Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats. Chem. Biol. Interact., 2007, 167(1), 12-18.
[http://dx.doi.org/10.1016/j.cbi.2006.12.011 ] [PMID: 17289008]
[26]
Dragojević-Simić, V.; Dobrić, S.; Jaćević, V.; Bokonjić, D.; Milosavljević, I.; Kovacević, A.; Mikić, D. Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats. Vojnosanit. Pregl., 2013, 70(1), 38-45.
[http://dx.doi.org/10.2298/VSP110905041D ] [PMID: 23401928]
[27]
Shivakumar, P.; Rani, M.U.; Reddy, A.G.; Anjaneyulu, Y. A study on the toxic effects of doxorubicin on the histology of certain organs. Toxicol. Int., 2012, 19(3), 241-244.
[http://dx.doi.org/10.4103/0971-6580.103656 ] [PMID: 23293460]
[28]
Pugazhendhi, A.; Edison, T.N.J.I.; Velmurugan, B.K.; Jacob, J.A.; Karuppusamy, I. Toxicity of doxorubicin (Dox) to different experimental organ systems. Life Sci., 2018, 200, 26-30.
[http://dx.doi.org/10.1016/j.lfs.2018.03.023 ] [PMID: 29534993]
[29]
Song, S.; Chu, L.; Liang, H.; Chen, J.; Liang, J.; Huang, Z.; Zhang, B.; Chen, X. Protective effects of dioscin against doxorubicin-induced hepatotoxicity via regulation of Sirt1/FOXO1/NF-κb signal. Front. Pharmacol., 2019, 10, 1030-1043.
[http://dx.doi.org/10.3389/fphar.2019.01030 ] [PMID: 31572199]
[30]
Yin, J.; Gao, Z.; Liu, D.; Liu, Z.; Ye, J. Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab., 2008, 294(1), E148-E156.
[http://dx.doi.org/10.1152/ajpendo.00211.2007 ] [PMID: 17971514]
[31]
Cicero, A.F.; Ertek, S.; Borghi, C. Omega-3 polyunsaturated fatty acids: their potential role in blood pressure prevention and management. Curr. Vasc. Pharmacol., 2009, 7(3), 330-337.
[http://dx.doi.org/10.2174/157016109788340659 ] [PMID: 19601857]
[32]
Prajapati, B.; Jena, P.K.; Rajput, P.; Purandhar, K.; Seshadri, S. Understanding and modulating the Toll like Receptors (TLRs) and NOD like Receptors (NLRs) cross talk in type 2 diabetes. Curr. Diabetes Rev., 2014, 10(3), 190-200.
[http://dx.doi.org/10.2174/1573399810666140515112609 ] [PMID: 24828062]
[33]
Wen, L.; Ley, R.E.; Volchkov, P.Y.; Stranges, P.B.; Avanesyan, L.; Stonebraker, A.C.; Hu, C.; Wong, F.S.; Szot, G.L.; Bluestone, J.A.; Gordon, J.I.; Chervonsky, A.V. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature, 2008, 455(7216), 1109-1113.
[http://dx.doi.org/10.1038/nature07336 ] [PMID: 18806780]
[34]
Yogalakshmi, B.; Viswanathan, P.; Anuradha, C.V. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology, 2010, 268(3), 204-212.
[http://dx.doi.org/10.1016/j.tox.2009.12.018 ] [PMID: 20036707]
[35]
Han, E.H.; Hwang, Y.P.; Jeong, T.C.; Lee, S.S.; Shin, J.G.; Jeong, H.G. Eugenol inhibit 7,12-dimethylbenz[a]anthracene-induced genotoxicity in MCF-7 cells: bifunctional effects on CYP1 and NAD(P)H:quinone oxidoreductase. FEBS Lett., 2007, 581(4), 749-756.
[http://dx.doi.org/10.1016/j.febslet.2007.01.044 ] [PMID: 17275817]
[36]
Chatuphonprasert, W.; Nemoto, N.; Sakuma, T.; Jarukamjorn, K. Modulations of cytochrome P450 expression in diabetic mice by berberine. Chem. Biol. Interact., 2012, 196(1-2), 23-29.
[http://dx.doi.org/10.1016/j.cbi.2012.01.006 ] [PMID: 22342832]

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