Xenobiotic Metabolising Enzymes: Impact on Pathologic Conditions, Drug Interactions and Drug Design

Author(s): Eleni A. Rekka*, Panos N. Kourounakis, Maria Pantelidou

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 4 , 2019

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Graphical Abstract:


Background: The biotransformation of xenobiotics is a homeostatic defensive response of the body against bioactive invaders. Xenobiotic metabolizing enzymes, important for the metabolism, elimination and detoxification of exogenous agents, are found in most tissues and organs and are distinguished into phase I and phase II enzymes, as well as phase III transporters. The cytochrome P450 superfamily of enzymes plays a major role in the biotransformation of most xenobiotics as well as in the metabolism of important endogenous substrates such as steroids and fatty acids. The activity and the potential toxicity of numerous drugs are strongly influenced by their biotransformation, mainly accomplished by the cytochrome P450 enzymes, one of the most versatile enzyme systems.

Objective: In this review, considering the importance of drug metabolising enzymes in health and disease, some of our previous research results are presented, which, combined with newer findings, may assist in the elucidation of xenobiotic metabolism and in the development of more efficient drugs.

Conclusion: Study of drug metabolism is of major importance for the development of drugs and provides insight into the control of human health. This review is an effort towards this direction and may find useful applications in related medical interventions or help in the development of more efficient drugs.

Keywords: Xenobiotic metabolism phase I II III, Cytochrome P450, Drug interactions, Drug design, Drug metabolising enzyme induction inhibition, Drug metabolism and pathologic conditions.

Zanger, U.M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol. Ther., 2013, 138(1), 103-141.
[http://dx.doi.org/10.1016/j.pharmthera.2012.12.007] [PMID: 23333322]
Tang, X.; Chen, S. Epigenetic regulation of cytochrome P450 enzymes and clinical implication. Curr. Drug Metab., 2015, 16(2), 86-96.
[http://dx.doi.org/10.2174/138920021602150713114159] [PMID: 26179605]
Raunio, H.; Kuusisto, M.; Juvonen, R.O.; Pentikäinen, O.T. Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes. Front. Pharmacol., 2015, 6, 123.
[http://dx.doi.org/10.3389/fphar.2015.00123] [PMID: 26124721]
du Souich, P.; Fradette, C. The effect and clinical consequences of hypoxia on cytochrome P450, membrane carrier proteins activity and expression. Expert Opin. Drug Metab. Toxicol., 2011, 7(9), 1083-1100.
[http://dx.doi.org/10.1517/17425255.2011.586630] [PMID: 21619472]
Li, M.; Zhao, Y.; Humar, A.; Tevar, A.D.; Hughes, C.; Venkataramanan, R. Pharmacokinetics of drugs in adult living donor liver transplant patients: regulatory factors and observations based on studies in animals and humans. Expert Opin. Drug Metab. Toxicol., 2016, 12(3), 231-243.
[http://dx.doi.org/10.1517/17425255. 2016.1139575] [PMID: 26809188]
Cescon, M.; Bertuzzo, V.R.; Ercolani, G.; Ravaioli, M.; Odaldi, F.; Pinna, A.D. Liver transplantation for hepatocellular carcinoma: role of inflammatory and immunological state on recurrence and prognosis. World J. Gastroenterol., 2013, 19(48), 9174-9182.
[http://dx.doi.org/10.3748/wjg.v19.i48.9174] [PMID: 24409045]
Bhogal, R.H.; Curbishley, S.M.; Weston, C.J.; Adams, D.H.; Afford, S.C. Reactive oxygen species mediate human hepatocyte injury during hypoxia/reoxygenation. Liver Transpl., 2010, 16(11), 1303-1313.
[http://dx.doi.org/10.1002/lt.22157] [PMID: 21031546]
Samarasinghe, D.A.; Tapner, M.; Farrell, G.C. Role of oxidative stress in hypoxia-reoxygenation injury to cultured rat hepatic sinusoidal endothelial cells. Hepatology, 2000, 31(1), 160-165.
[http://dx.doi.org/10.1002/hep.510310124] [PMID: 10613741]
Rekka, E.; Evdokimova, E.; Eeckhaudt, S.; Calderon, P.B. Reoxygenation after cold hypoxic storage of cultured precision-cut rat liver slices: effects on cellular metabolism and drug biotransformation. Biochim. Biophys. Acta, 2001, 1568(3), 245-251.
[http://dx.doi.org/10.1016/S0304-4165(01)00225-2] [PMID: 11786231]
Westerholt, A.; Himpel, S.; Hager-Gensch, B.; Maier, S.; Werner, M.; Stadler, J.; Doehmer, J.; Heidecke, C.D. Intragraft iNOS induction during human liver allograft rejection depresses cytochrome p450 activity. Transpl. Int., 2004, 17(7), 370-378.
[http://dx.doi.org/10.1111/j.1432-2277.2004.tb00457.x] [PMID: 15349722]
Matevossian, E.; Novotny, A.; Knebel, C.; Brill, T.; Werner, M.; Sinicina, I.; Kriner, M.; Stangl, M.; Thorban, S.; Hüser, N. The effect of selective inhibition of inducible nitric oxide synthase on cytochrome P450 after liver transplantation in a rat model. Transplant. Proc., 2008, 40(4), 983-985.
[http://dx.doi.org/10.1016/j.transproceed.2008.04.001] [PMID: 18555096]
Szabo, S.; Kourounakis, P.; Selye, H. Effect of adrenocorticotropin (ACTH) upon the drug response of intact and adrenalectomized rats. Can. J. Physiol. Pharmacol., 1973, 51(3), 169-174.
[http://dx.doi.org/10.1139/y73-024] [PMID: 4350179]
Salas, M.; Tuchweber, B.; Kourounakis, P.; Selye, H. Temperature-dependence of stress-induced hepatic autophagy. Experientia, 1977, 33(5), 612-614.
[http://dx.doi.org/10.1007/BF01946531] [PMID: 862791]
Pantelidou, M.; Tsiakitzis, K.; Rekka, E.A.; Kourounakis, P.N. Biologic stress, oxidative stress, and resistance to drugs: What is hidden behind. Molecules, 2017, 22(2), E307.
[http://dx.doi.org/10.3390/molecules22020307] [PMID: 28218677]
Driever, C.W.; Bousquet, W.F.; Miya, T.S. Stress stimulation of drug metabolism in the rat. Int. J. Neuropharmacol., 1966, 5(2), 199-205.
[http://dx.doi.org/10.1016/0028-3908(66)90023-2] [PMID: 4289630]
Belda, X.; Fuentes, S.; Daviu, N.; Nadal, R.; Armario, A. Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond. Stress, 2015, 18(3), 269-279.
[http://dx.doi.org/10.3109/10253890.2015.1067678] [PMID: 26300109]
Kourounakis, P.N.; Rekka, E. Induction of drug metabolism can be a homeostatic response. Arch. Pharm. (Weinheim), 1991, 324(3), 161-164.
[http://dx.doi.org/10.1002/ardp.19913240306] [PMID: 1859251]
Volk, C.; Gorboulev, V.; Kotzsch, A.; Müller, T.D.; Koepsell, H. Five amino acids in the innermost cavity of the substrate binding cleft of organic cation transporter 1 interact with extracellular and intracellular corticosterone. Mol. Pharmacol., 2009, 76(2), 275-289.
[http://dx.doi.org/10.1124/mol.109.054783] [PMID: 19435783]
Selye, H. Stress in health and disease; Butterworths: Boston, London, 1976.
Selye, H. Stress and disease. Science, 1955, 122(3171), 625-631.
[http://dx.doi.org/10.1126/science.122.3171.625] [PMID: 13255902]
Sies, H. Oxidative stress: oxidants and antioxidants. Exp. Physiol., 1997, 82(2), 291-295.
[http://dx.doi.org/10.1113/expphysiol.1997. sp004024] [PMID: 9129943]
Tsiakitzis, K.; Kourounakis, A.P.; Tani, E.; Rekka, E.A.; Kourounakis, P.N. Stress and active oxygen species--effect of alpha-tocopherol on stress response. Arch. Pharm. (Weinheim), 2005, 338(7), 315-321.
[http://dx.doi.org/10.1002/ardp.200400946] [PMID: 15981300]
Brigelius-Flohé, R. Vitamin E and drug metabolism. Biochem. Biophys. Res. Commun., 2003, 305(3), 737-740.
[http://dx.doi.org/ 10.1016/S0006-291X(03)00811-8] [PMID: 12763054]
Johnson, C.H.; Bonzo, J.A.; Cheng, J.; Krausz, K.W.; Kang, D.W.; Luecke, H.; Idle, J.R.; Gonzalez, F.J. Cytochrome P450 regulation by α-tocopherol in Pxr-null and PXR-humanized mice. Drug Metab. Dispos., 2013, 41(2), 406-413.
[http://dx.doi.org/10.1124/dmd.112.048009] [PMID: 23160821]
Landes, N.; Pfluger, P.; Kluth, D.; Birringer, M.; Rühl, R.; Böl, G.F.; Glatt, H.; Brigelius-Flohé, R. Vitamin E activates gene expression via the pregnane X receptor. Biochem. Pharmacol., 2003, 65(2), 269-273.
[http://dx.doi.org/10.1016/S0006-2952(02)01520-4] [PMID: 12504802]
Toivonen, M.L.; Tokola, O.; Vapaatalo, H. Rat adjuvant arthritis as a model to test potential antirheumatic agents. Methods Find. Exp. Clin. Pharmacol., 1982, 4(6), 359-363.
[PMID: 7144330]
Rajendran, R.; Krishnakumar, E. Anti-arthritic activity of Premna serratifolia Linn., wood against Adjuvant Induced Arthritis. Avicenna J. Med. Biotechnol., 2010, 2(2), 101-106.
[PMID: 23407688]
Kourounakis, P.; Hadjipetrou-Kourounakis, L. Effect of pregnenolone-16 alpha-carbonitrile and other microsomal enzyme inducers on drug metabolism and some parameters of adjuvant induced disease in rats. Pharm. Acta Helv., 1984, 59(12), 348-352.
[PMID: 6522414]
Toda, A.; Ishii, N.; Kihara, T.; Nagamatsu, A.; Shimeno, H. Effect of adjuvant-induced arthritis on hepatic drug metabolism in rats. Xenobiotica, 1994, 24(7), 603-611.
[http://dx.doi.org/10.3109/00498259409043263] [PMID: 7975725]
Kourounakis, P.N.; Rekka, E.; Hadjipetrou-Kourounakis, L. Restoration of impaired drug metabolism of rats with adjuvant induced disease by two steroids with different influence on drug biotransformation. Pharmazie, 1991, 46(10), 727-729.
[PMID: 1803389]
Ling, S.; Jamali, F. Effect of early phase adjuvant arthritis on hepatic P450 enzymes and pharmacokinetics of verapamil: an alternative approach to the use of an animal model of inflammation for pharmacokinetic studies. Drug Metab. Dispos., 2005, 33(4), 579-586.
[http://dx.doi.org/10.1124/dmd.104.002360] [PMID: 15659540]
Sanada, H.; Sekimoto, M.; Kamoshita, A.; Degawa, M. Changes in expression of hepatic cytochrome P450 subfamily enzymes during development of adjuvant-induced arthritis in rats. J. Toxicol. Sci., 2011, 36(2), 181-190.
[http://dx.doi.org/10.2131/jts.36.181] [PMID: 21467745]
Thiebaud, N.; Sigoillot, M.; Chevalier, J.; Artur, Y.; Heydel, J.M.; Le Bon, A.M. Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats. Drug Metab. Dispos., 2010, 38(10), 1865-1875.
[http://dx.doi.org/10.1124/dmd.110.035014] [PMID: 20639433]
Duca, R.C.; Mabondzo, A.; Bravin, F.; Delaforge, M. In vivo effects of zearalenone on the expression of proteins involved in the detoxification of rat xenobiotics. Environ. Toxicol., 2012, 27(2), 98-108.
[http://dx.doi.org/10.1002/tox.20617] [PMID: 20607812]
Norlin, M.; Wikvall, K. Enzymes in the conversion of cholesterol into bile acids. Curr. Mol. Med., 2007, 7(2), 199-218.
[http://dx.doi.org/10.2174/156652407780059168] [PMID: 17346171]
Björkhem, I.; Cedazo-Minguez, A.; Leoni, V.; Meaney, S. Oxysterols and neurodegenerative diseases. Mol. Aspects Med., 2009, 30(3), 171-179.
[http://dx.doi.org/10.1016/j.mam.2009.02.001] [PMID: 19248803]
Rekka, E.; Gouma, C.; Kourounakis, P. In vivo interaction of spironolactone and phenobarbital with cholesterol; effect on cholesterol organ concentration. Pharmazie, 1987, 42(2), 107-108.
[PMID: 3602047]
Lake, B.G. Species differences in the hepatic effects of inducers of CYP2B and CYP4A subfamily forms: relationship to rodent liver tumour formation. Xenobiotica, 2009, 39(8), 582-596.
[http://dx.doi.org/ 10.1080/00498250903098184] [PMID: 19622001]
El-Sayed, W.M. Effect of pregnane X receptor (PXR) prototype agonists on chemoprotective and drug metabolizing enzymes in mice. Eur. J. Pharmacol., 2011, 660(2-3), 291-297.
[http://dx.doi.org/ 10.1016/j.ejphar.2011.03.047] [PMID: 21496454]
Wada, T.; Kenmochi, H.; Miyashita, Y.; Sasaki, M.; Ojima, M.; Sasahara, M.; Koya, D.; Tsuneki, H.; Sasaoka, T. Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. Endocrinology, 2010, 151(5), 2040-2049.
[http://dx.doi.org/10.1210/en.2009-0869] [PMID: 20211973]
Bachmann, K.; Patel, H.; Batayneh, Z.; Slama, J.; White, D.; Posey, J.; Ekins, S.; Gold, D.; Sambucetti, L. PXR and the regulation of apoA1 and HDL-cholesterol in rodents. Pharmacol. Res., 2004, 50(3), 237-246.
[http://dx.doi.org/10.1016/j.phrs.2004.03.005] [PMID: 15225665]
Dinh, Q.N.; Young, M.J.; Evans, M.A.; Drummond, G.R.; Sobey, C.G.; Chrissobolis, S. Aldosterone-induced oxidative stress and inflammation in the brain are mediated by the endothelial cell mineralocorticoid receptor. Brain Res., 2016, 1637, 146-153.
[http://dx.doi.org/10.1016/j.brainres.2016.02.034] [PMID: 26923165]
Sharma, A.; Hamelin, B.A. Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird’s eye view. Curr. Drug Metab., 2003, 4(2), 105-129.
[http://dx.doi.org/10.2174/1389200033489523] [PMID: 12678691]
Flockhart, D.A.; Desta, Z.; Mahal, S.K. Selection of drugs to treat gastro-oesophageal reflux disease: the role of drug interactions. Clin. Pharmacokinet., 2000, 39(4), 295-309.
[http://dx.doi.org/ 10.2165/00003088-200039040-00005] [PMID: 11069215]
Zhou, Q.; Yan, X.F.; Zhang, Z.M.; Pan, W.S.; Zeng, S. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions. World J. Gastroenterol., 2007, 13(42), 5618-5628.
[http://dx.doi.org/10.3748/wjg.v13.i42.5618] [PMID: 17948937]
Rekka, E.; Timmermann, H.; Bast, A. Structural features of some diphenhydramine analogues that determine the interaction with rat liver cytochrome P-450. Agents Actions, 1989, 27(1-2), 184-187.
[http://dx.doi.org/10.1007/BF02222234] [PMID: 2750591]
Hiroi, T.; Ohishi, N.; Imaoka, S.; Yabusaki, Y.; Fukui, H.; Funae, Y. Mepyramine, a histamine H1 receptor antagonist, inhibits the metabolic activity of rat and human P450 2D forms. J. Pharmacol. Exp. Ther., 1995, 272(2), 939-944.
[PMID: 7853212]
Moody, D.E.; Liu, F.; Fang, W.B. In vitro inhibition of methadone and oxycodone cytochrome P450-dependent metabolism: reversible inhibition by H2-receptor agonists and proton-pump inhibitors. J. Anal. Toxicol., 2013, 37(8), 476-485.
[http://dx.doi.org/10.1093/jat/bkt060] [PMID: 23857299]
Stadel, R.; Yang, J.; Nalwalk, J.W.; Phillips, J.G.; Hough, L.B. High-affinity binding of [3H]cimetidine to a heme-containing protein in rat brain. Drug Metab. Dispos., 2008, 36(3), 614-621.
[http://dx.doi.org/10.1124/dmd.107.017889] [PMID: 18094038]
Kudo, T.; Endo, Y.; Taguchi, R.; Yatsu, M.; Ito, K. Metronidazole reduces the expression of cytochrome P450 enzymes in HepaRG cells and cryopreserved human hepatocytes. Xenobiotica, 2015, 45(5), 413-419.
[http://dx.doi.org/10.3109/00498254.2014.990948] [PMID: 25470432]
Niwa, T.; Imagawa, Y.; Yamazaki, H. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr. Drug Metab., 2014, 15(7), 651-679.
[http://dx.doi.org/10.2174/1389200215666141125121511] [PMID: 25429674]
Zhou, Q.; Yan, X.F.; Zhang, Z.M.; Pan, W.S.; Zeng, S. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions. World J. Gastroenterol., 2007, 13(42), 5618-5628.
[http://dx.doi.org/10.3748/wjg.v13.i42.5618] [PMID: 17948937]
Rekka, E.; Sterk, G.J.; Timmerman, H.; Bast, A. Identification of structural characteristics of some potential H2-receptor antagonists that determine the interaction with rat hepatic P-450. Chem. Biol. Interact., 1988, 67(1-2), 117-127.
[http://dx.doi.org/10.1016/0009-2797(88)90091-9] [PMID: 2901918]
Fleming, I.; Michaelis, U.R.; Bredenkötter, D.; Fisslthaler, B.; Dehghani, F.; Brandes, R.P.; Busse, R. Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ. Res., 2001, 88(1), 44-51.
[http://dx.doi.org/ 10.1161/01.RES.88.1.44] [PMID: 11139472]
Rendic, S.; Di Carlo, F.J. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev., 1997, 29(1-2), 413-580.
[http://dx.doi.org/10.3109/03602539709037591] [PMID: 9187528]
Granville, D.J.; Tashakkor, B.; Takeuchi, C.; Gustafsson, A.B.; Huang, C.; Sayen, M.R.; Wentworth, P., Jr; Yeager, M.; Gottlieb, R.A. Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. Proc. Natl. Acad. Sci. USA, 2004, 101(5), 1321-1326.
[http://dx.doi.org/10.1073/pnas.0308185100] [PMID: 14734800]
König, J.; Müller, F.; Fromm, M.F. Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacol. Rev., 2013, 65(3), 944-966.
[http://dx.doi.org/10.1124/pr.113.007518] [PMID: 23686349]
Iwata, K.; Aizawa, K.; Kamitsu, S.; Jingami, S.; Fukunaga, E.; Yoshida, M.; Yoshimura, M.; Hamada, A.; Saito, H. Effects of genetic variants in SLC22A2 organic cation transporter 2 and SLC47A1 multidrug and toxin extrusion 1 transporter on cisplatin-induced adverse events. Clin. Exp. Nephrol., 2012, 16(6), 843-851.
[http://dx.doi.org/10.1007/s10157-012-0638-y] [PMID: 22569819]
Katsuda, H.; Yamashita, M.; Katsura, H.; Yu, J.; Waki, Y.; Nagata, N.; Sai, Y.; Miyamoto, K. Protecting cisplatin-induced nephrotoxicity with cimetidine does not affect antitumor activity. Biol. Pharm. Bull., 2010, 33(11), 1867-1871.
[http://dx.doi.org/ 10.1248/bpb.33.1867] [PMID: 21048313]
Ciarimboli, G. Membrane transporters as mediators of cisplatin side-effects. Anticancer Res., 2014, 34(1), 547-550.
[PMID: 24403515]
Kourounakis, P.; Rekka, E. Interaction of ethanol with drugs; Effect on drug activity, metabolism and hepatic function. A comparative study with known microsomal enzyme inducers. Sci. Pharm., 1987, 55, 49-55.
Feierman, D.E.; Melinkov, Z.; Nanji, A.A. Induction of CYP3A by ethanol in multiple in vitro and in vivo models. Alcohol. Clin. Exp. Res., 2003, 27(6), 981-988.
[http://dx.doi.org/10.1111/j.1530-0277.2003.tb04424.x] [PMID: 12824820]
Grant, S.K.; Green, B.G.; Wang, R.; Pacholok, S.G.; Kozarich, J.W. Characterization of inducible nitric-oxide synthase by cytochrome P-450 substrates and inhibitors. Inhibition by chlorzoxazone. J. Biol. Chem., 1997, 272(2), 977-983.
[http://dx.doi.org/ 10.1074/jbc.272.2.977] [PMID: 8995391]
Arlotto, M.P.; Sonderfan, A.J.; Klaassen, C.D.; Parkinson, A. Studies on the pregnenolone-16 alpha-carbonitrile-inducible form of rat liver microsomal cytochrome P-450 and UDP-glucuronosyltransferase. Biochem. Pharmacol., 1987, 36(22), 3859-3866.
[http://dx.doi.org/10.1016/0006-2952(87)90450-3] [PMID: 3120728]
Arlotto, M.P.; Sonderfan, A.J.; McKinney, M.M.; Parkinson, A. Digitoxin metabolism by liver microsomal cytochrome P-450 and UDP-glucuronosyltransferase and its role in the protection of rats from digitoxin toxicity by pregnenolone-16 alpha-carbonitrile. Arch. Biochem. Biophys., 1986, 251(1), 188-197.
[http://dx.doi.org/ 10.1016/0003-9861(86)90065-2] [PMID: 3098175]
Wirth, K.E.; Frölich, J.C.; Hollifield, J.W.; Falkner, F.C.; Sweetman, B.S.; Oates, J.A. Metabolism of digitoxin in man and its modification by spironolactone. Eur. J. Clin. Pharmacol., 1976, 09(5-6), 345-354.
[http://dx.doi.org/10.1007/BF00606547] [PMID: 971699]
Hazelton, G.A.; Klaassen, C.D. UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside. Differences in activation and induction properties in rat and mouse liver. Drug Metab. Dispos., 1988, 16(1), 30-36.
[PMID: 2894952]
Theile, D.; Schmidt, T.T.; Haefeli, W.E.; Weiss, J. In-vitro evaluation of chronic alcohol effects on expression of drug-metabolizing and drug-transporting proteins. J. Pharm. Pharmacol., 2013, 65(10), 1518-1525.
[http://dx.doi.org/10.1111/jphp.12124] [PMID: 24028619]
Gozalpour, E.; Wittgen, H.G.; van den Heuvel, J.J.; Greupink, R.; Russel, F.G.; Koenderink, J.B. Interaction of digitalis-like compounds with p-glycoprotein. Toxicol. Sci., 2013, 131(2), 502-511.
[http://dx.doi.org/10.1093/toxsci/kfs307] [PMID: 23104431]
Salphati, L.; Benet, L.Z. Modulation of P-glycoprotein expression by cytochrome P450 3A inducers in male and female rat livers. Biochem. Pharmacol., 1998, 55(4), 387-395.
[http://dx.doi.org/ 10.1016/S0006-2952(97)00436-X] [PMID: 9514072]
Duggan, D.E.; Hogans, A.F.; Kwan, K.C.; McMahon, F.G. The metabolism of indomethacin in man. J. Pharmacol. Exp. Ther., 1972, 181(3), 563-575.
[PMID: 4555898]
Nakajima, M.; Inoue, T.; Shimada, N.; Tokudome, S.; Yamamoto, T.; Kuroiwa, Y. Cytochrome P450 2C9 catalyzes indomethacin O-demethylation in human liver microsomes. Drug Metab. Dispos., 1998, 26(3), 261-266.
[PMID: 9492390]
Kuehl, G.E.; Lampe, J.W.; Potter, J.D.; Bigler, J. Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab. Dispos., 2005, 33(7), 1027-1035.
[http://dx.doi.org/ 10.1124/dmd.104.002527] [PMID: 15843492]
Buckley, D.B.; Klaassen, C.D. Induction of mouse UDP-glucuronosyltransferase mRNA expression in liver and intestine by activators of aryl-hydrocarbon receptor, constitutive androstane receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and nuclear factor erythroid 2-related factor 2. Drug Metab. Dispos., 2009, 37(4), 847-856.
[http://dx.doi.org/ 10.1124/dmd.108.024190] [PMID: 19144771]
Amacher, D.E.; Schomaker, S.J. Ethylmorphine N-demethylase activity as a marker for cytochrome P450 CYP3A activity in rat hepatic microsomes. Toxicol. Lett., 1998, 94(2), 115-125.
[http://dx.doi.org/10.1016/S0378-4274(97)00108-2] [PMID: 9574808]
Sakalli, S.; Burkina, V.; Zlabek, V.; Zamaratskaia, G. Effects of acetone, acetonitrile, ethanol, methanol and DMSO on cytochrome P450 in rainbow trout (Oncorhynchus mykiss) hepatic microsomes. Toxicol. Mech. Methods, 2015, 25(6), 501-506.
[PMID: 26275123]
Wolf, K.K.; Wood, S.G.; Allard, J.L.; Hunt, J.A.; Gorman, N.; Walton-Strong, B.W.; Szakacs, J.G.; Duan, S.X.; Hao, Q.; Court, M.H.; von Moltke, L.L.; Greenblatt, D.J.; Kostrubsky, V.; Jeffery, E.H.; Wrighton, S.A.; Gonzalez, F.J.; Sinclair, P.R.; Sinclair, J.F. Role of CYP3A and CYP2E1 in alcohol-mediated increases in acetaminophen hepatotoxicity: comparison of wild-type and Cyp2e1(-/-) mice. Drug Metab. Dispos., 2007, 35(7), 1223-1231.
[http://dx.doi.org/10.1124/dmd.107.014738] [PMID: 17392391]
Luceri, F.; Fattori, S.; Luceri, C.; Zorn, M.; Mannaioni, P.; Messeri, G. Gas chromatography-mass spectrometry measurement of 6beta-OH-cortisol/cortisol ratio in human urine: a specific marker of enzymatic induction. Clin. Chem. Lab. Med., 2001, 39(12), 1234-1239.
[http://dx.doi.org/10.1515/CCLM.2001.198] [PMID: 11798083]
St Haxholdt, O.; Krintel, J.J.; Johansson, G. Pre-operative alcohol infusion. The need for analgesic supplementation in chronic alcoholics. Anaesthesia, 1984, 39(3), 240-245.
[http://dx.doi.org/ 10.1111/j.1365-2044.1984.tb07234.x] [PMID: 6703291]
Kumar, S.; Jin, M.; Ande, A.; Sinha, N.; Silverstein, P.S.; Kumar, A. Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes. Expert Opin. Drug Metab. Toxicol., 2012, 8(11), 1363-1375.
[http://dx.doi.org/10.1517/17425255.2012.714366] [PMID: 22871069]
Mori, Y.; Koide, A.; Kobayashi, Y.; Morimura, K.; Kaneko, M.; Fukushima, S. Effect of ethanol treatment on metabolic activation and detoxification of esophagus carcinogenic N-nitrosamines in rat liver. Mutagenesis, 2002, 17(3), 251-256.
[http://dx.doi.org/ 10.1093/mutage/17.3.251] [PMID: 11971997]
Lotan, R. Retinoids in cancer chemoprevention. FASEB J., 1996, 10(9), 1031-1039.
[http://dx.doi.org/10.1096/fasebj.10.9.8801164] [PMID: 8801164]
Liu, C.; Russell, R.M.; Seitz, H.K.; Wang, X.D. Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1. Gastroenterology, 2001, 120(1), 179-189.
[http://dx.doi.org/10.1053/gast.2001.20877] [PMID: 11208727]
Ingelman-Sundberg, M.; Johansson, I.; Yin, H.; Terelius, Y.; Eliasson, E.; Clot, P.; Albano, E. Ethanol-inducible cytochrome P4502E1: genetic polymorphism, regulation, and possible role in the etiology of alcohol-induced liver disease. Alcohol, 1993, 10(6), 447-452.
[http://dx.doi.org/10.1016/0741-8329(93)90063-T] [PMID: 8123198]
Neafsey, P.; Ginsberg, G.; Hattis, D.; Johns, D.O.; Guyton, K.Z.; Sonawane, B. Genetic polymorphism in CYP2E1: Population distribution of CYP2E1 activity. J. Toxicol. Environ. Health B Crit. Rev., 2009, 12(5-6), 362-388.
[http://dx.doi.org/10.1080/10937400903158359] [PMID: 20183527]
Leung, T.; Rajendran, R.; Singh, S.; Garva, R.; Krstic-Demonacos, M.; Demonacos, C. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells. Breast Cancer Res., 2013, 15(6), R107.
[http://dx.doi.org/10.1186/bcr3574] [PMID: 24207099]
Zimatkin, S.M.; Pronko, S.P.; Vasiliou, V.; Gonzalez, F.J.; Deitrich, R.A. Enzymatic mechanisms of ethanol oxidation in the brain. Alcohol. Clin. Exp. Res., 2006, 30(9), 1500-1505.
[http://dx.doi.org/10.1111/j.1530-0277.2006.00181.x] [PMID: 16930212]
Ledesma, J.C.; Miquel, M.; Pascual, M.; Guerri, C.; Aragon, C.M. Induction of brain cytochrome P450 2E1 boosts the locomotor-stimulating effects of ethanol in mice. Neuropharmacology, 2014, 85, 36-44.
[http://dx.doi.org/10.1016/j.neuropharm.2014.05.018] [PMID: 24863043]
Takahashi, S.; Takahashi, T.; Mizobuchi, S.; Matsumi, M.; Yokoyama, M.; Morita, K.; Miyazaki, M.; Namba, M.; Akagi, R.; Sassa, S. CYP2E1 overexpression up-regulates both non-specific delta-aminolevulinate synthase and heme oxygenase-1 in the human hepatoma cell line HLE/2E1. Int. J. Mol. Med., 2003, 11(1), 57-62.
[PMID: 12469218]
Gong, P.; Cederbaum, A.I.; Nieto, N. Increased expression of cytochrome P450 2E1 induces heme oxygenase-1 through ERK MAPK pathway. J. Biol. Chem., 2003, 278(32), 29693-29700.
[http://dx.doi.org/10.1074/jbc.M304728200] [PMID: 12777398]
Liu, L.G.; Yan, H.; Zhang, W.; Yao, P.; Zhang, X.P.; Sun, X.F.; Nussler, A.K. Induction of heme oxygenase-1 in human hepatocytes to protect them from ethanol-induced cytotoxicity. Biomed. Environ. Sci., 2004, 17(3), 315-326.
[PMID: 15602829]
Hardwick, J.P. Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases. Biochem. Pharmacol., 2008, 75(12), 2263-2275.
[http://dx.doi.org/10.1016/j.bcp.2008.03.004] [PMID: 18433732]
Edson, K.Z.; Rettie, A.E. CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities. Curr. Top. Med. Chem., 2013, 13(12), 1429-1440.
[http://dx.doi.org/10.2174/15680266113139990110] [PMID: 23688133]
Johnson, A.L.; Edson, K.Z.; Totah, R.A.; Rettie, A.E. Cytochrome P450 ω-hydroxylases in inflammation and cancer. Adv. Pharmacol., 2015, 74, 223-262.
[http://dx.doi.org/10.1016/bs.apha.2015.05.002] [PMID: 26233909]
Edson, K.Z.; Rettie, A.E. CYP4 enzymes as potential drug targets: focus on enzyme multiplicity, inducers and inhibitors, and therapeutic modulation of 20-hydroxyeicosatetraenoic acid (20-HETE) synthase and fatty acid ω-hydroxylase activities. Curr. Top. Med. Chem., 2013, 13(12), 1429-1440.
[http://dx.doi.org/10.2174/15680266113139990110] [PMID: 23688133]
Kirischian, N.L.; Wilson, J.Y. Phylogenetic and functional analyses of the cytochrome P450 family 4. Mol. Phylogenet. Evol., 2012, 62(1), 458-471.
[http://dx.doi.org/10.1016/j.ympev.2011.10.016] [PMID: 22079551]
Hakkola, J.; Bernasconi, C.; Coecke, S.; Richert, L.; Andersson, T.B.; Pelkonen, O. Cytochrome P450 induction and xeno-sensing receptors pregnane X receptor, constitutive androstane receptor, aryl hydrocarbon receptor and peroxisome proliferator-activated receptor α at the crossroads of toxicokinetics and toxicodynamics. Basic Clin. Pharmacol. Toxicol., 2018, 123(Suppl. 5), 42-50.
[http://dx.doi.org/10.1111/bcpt.13004] [PMID: 29527807]
Shelby, M.K.; Klaassen, C.D. Induction of rat UDP-glucuronosyltransferases in liver and duodenum by microsomal enzyme inducers that activate various transcriptional pathways. Drug Metab. Dispos., 2006, 34(10), 1772-1778.
[http://dx.doi.org/ 10.1124/dmd.106.010397] [PMID: 16855052]
Zhou, Y.; Huang, H.; Chang, H.H.; Du, J.; Wu, J.F.; Wang, C.Y.; Wang, M.H. Induction of renal 20-hydroxyeicosatetraenoic acid by clofibrate attenuates high-fat diet-induced hypertension in rats. J. Pharmacol. Exp. Ther., 2006, 317(1), 11-18.
[http://dx.doi.org/ 10.1124/jpet.105.095356] [PMID: 16339392]
Nishimura, J.; Dewa, Y.; Okamura, T.; Muguruma, M.; Jin, M.; Saegusa, Y.; Umemura, T.; Mitsumori, K. Possible involvement of oxidative stress in fenofibrate-induced hepatocarcinogenesis in rats. Arch. Toxicol., 2008, 82(9), 641-654.
[http://dx.doi.org/10.1007/s00204-007-0278-2] [PMID: 18253720]
Zhao, X.; Li, L.Y. PPAR-alpha agonist fenofibrate induces renal CYP enzymes and reduces blood pressure and glomerular hypertrophy in Zucker diabetic fatty rats. Am. J. Nephrol., 2008, 28(4), 598-606.
[http://dx.doi.org/10.1159/000116885] [PMID: 18277067]
Ayrton, A.D.; Ioannides, C.; Parke, D.V. Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity. Biochem. Pharmacol., 1991, 42(1), 109-115.
[http://dx.doi.org/10.1016/0006-2952(91)90688-2] [PMID: 2069584]
Rekka, E.; Ayalogu, E.O.; Lewis, D.F.; Gibson, G.G.; Ioannides, C. Induction of hepatic microsomal CYP4A activity and of peroxisomal beta-oxidation by two non-steroidal anti-inflammatory drugs. Arch. Toxicol., 1994, 68(2), 73-78.
[http://dx.doi.org/10.1007/s002040050037] [PMID: 8179485]
Bambal, R.B.; Hanzlik, R.P. Effects of steric bulk and conformational rigidity on fatty acid omega hydroxylation by a cytochrome P450 4A1 fusion protein. Arch. Biochem. Biophys., 1996, 334(1), 59-66.
[http://dx.doi.org/10.1006/abbi.1996.0429] [PMID: 8837739]
Dong, J.Q.; Liu, J.; Smith, P.C. Role of benoxaprofen and flunoxaprofen acyl glucuronides in covalent binding to rat plasma and liver proteins in vivo. Biochem. Pharmacol., 2005, 70(6), 937-948.
[http://dx.doi.org/10.1016/j.bcp.2005.05.026] [PMID: 16046212]
Dong, J.Q.; Smith, P.C. Glucuronidation and covalent protein binding of benoxaprofen and flunoxaprofen in sandwich-cultured rat and human hepatocytes. Drug Metab. Dispos., 2009, 37(12), 2314-2322.
[http://dx.doi.org/10.1124/dmd.109.028944] [PMID: 19773537]
Qiu, Y.; Burlingame, A.L.; Benet, L.Z. Mechanisms for covalent binding of benoxaprofen glucuronide to human serum albumin. Studies By tandem mass spectrometry. Drug Metab. Dispos., 1998, 26(3), 246-256.
[PMID: 9492388]
Sallustio, B.C.; Degraaf, Y.C.; Weekley, J.S.; Burcham, P.C. Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity. Chem. Res. Toxicol., 2006, 19(5), 683-691.
[http://dx.doi.org/10.1021/tx060022k] [PMID: 16696571]
Aleksunes, L.M.; Klaassen, C.D. Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARα-, and Nrf2-null mice. Drug Metab. Dispos., 2012, 40(7), 1366-1379.
[http://dx.doi.org/ 10.1124/dmd.112.045112] [PMID: 22496397]
Nebert, D.W.; Wikvall, K.; Miller, W.L. Human cytochromes P450 in health and disease. Philos. Trans. R. Soc. Lond. B Biol. Sci., 2013, 368(1612), 20120431.
[http://dx.doi.org/ 10.1098/rstb. 2012.0431] [PMID: 23297354]
Park, E.C.; Kim, S.I.; Hong, Y.; Hwang, J.W.; Cho, G.S.; Cha, H.N.; Han, J.K.; Yun, C.H.; Park, S.Y.; Jang, I.S.; Lee, Z.W.; Choi, J.S.; Kim, S.; Kim, G.H. Inhibition of CYP4A reduces hepatic endoplasmic reticulum stress and features of diabetes in mice. Gastroenterology, 2014, 147(4), 860-869.
[http://dx.doi.org/ 10.1053/j.gastro.2014.06.039] [PMID: 24983671]
Wilson, J.L.; Duan, R.; El-Marakby, A.; Alhashim, A.; Lee, D.L. Peroxisome proliferator activated receptor-α agonist slows the progression of hypertension, attenuates plasma interleukin-6 levels and renal inflammatory markers in angiotensin II infused mice. PPAR Res., 2012, 2012, 645969.
[http://dx.doi.org/10.1155/2012/645969] [PMID: 22848208]
Alsaad, A.M.; Zordoky, B.N.; El-Sherbeni, A.A.; El-Kadi, A.O. Chronic doxorubicin cardiotoxicity modulates cardiac cytochrome P450-mediated arachidonic acid metabolism in rats. Drug Metab. Dispos., 2012, 40(11), 2126-2135.
[http://dx.doi.org/10.1124/dmd.112.046631] [PMID: 22867862]
Maser, E. Xenobiotic carbonyl reduction and physiological steroid oxidoreduction. The pluripotency of several hydroxysteroid dehydrogenases. Biochem. Pharmacol., 1995, 49(4), 421-440.
[http://dx.doi.org/10.1016/0006-2952(94)00330-O] [PMID: 7872949]
Hoffmann, F.; Maser, E. Carbonyl reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/reductase superfamily. Drug Metab. Rev., 2007, 39(1), 87-144.
[http://dx.doi.org/10.1080/03602530600969440] [PMID: 17364882]
Niwa, R.; Niwa, Y.S. Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond. Biosci. Biotechnol. Biochem., 2014, 78(8), 1283-1292.
[http://dx.doi.org/10.1080/09168451.2014.942250] [PMID: 25130728]
Ciato, D.; Mumbach, A.G.; Paez-Pereda, M.; Stalla, G.K. Currently used and investigational drugs for Cushing’s disease. Expert Opin. Investig. Drugs, 2017, 26(1), 75-84.
[http://dx.doi.org/10.1080/13543784.2017.1266338] [PMID: 27894193]
Belai, I.; Darvas, B.; Bauer, K.; Tag El-Din, M. Effects of anti-ecdysteroid azole analogues of metyrapone on the larval development of the fleshfly, Neobellieria bullata. Pestic. Sci., 1995, 44, 225-232.
Rekka, E.A.; Soldan, M.; Belai, I.; Netter, K.J.; Maser, E. Biotransformation and detoxification of insecticidal metyrapone analogues by carbonyl reduction in the human liver. Xenobiotica, 1996, 26(12), 1221-1229.
[http://dx.doi.org/10.3109/00498259609047226] [PMID: 9004452]
Gulliford, M.C.; Charlton, J.; Latinovic, R. Risk of diabetes associated with prescribed glucocorticoids in a large population. Diabetes Care, 2006, 29(12), 2728-2729.
[http://dx.doi.org/10.2337/dc06-1499] [PMID: 17130214]
Baudrand, R.; Campino, C.; Carvajal, C.A.; Olivieri, O.; Guidi, G.; Faccini, G.; Sateler, J.; Cornejo, J.; Martin, B.S.; Dominguez, J.M.; Cerda, J.; Mosso, L.M.; Owen, G.I.; Kalergis, A.M.; Fardella, C.E. Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction. Steroids, 2011, 76(14), 1575-1581.
[http://dx.doi.org/10.1016/j.steroids.2011.09.010] [PMID: 21996535]
Morton, N.M.; Paterson, J.M.; Masuzaki, H.; Holmes, M.C.; Staels, B.; Fievet, C.; Walker, B.R.; Flier, J.S.; Mullins, J.J.; Seckl, J.R. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 β-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes, 2004, 53(4), 931-938.
[http://dx.doi.org/10.2337/diabetes.53.4.931] [PMID: 15047607]
Harno, E.; Cottrell, E.C.; Keevil, B.G.; DeSchoolmeester, J.; Bohlooly-Y, M.; Andersén, H.; Turnbull, A.V.; Leighton, B.; White, A. 11-Dehydrocorticosterone causes metabolic syndrome, which is prevented when 11β-HSD1 is knocked out in livers of male mice. Endocrinology, 2013, 154(10), 3599-3609.
[http://dx.doi.org/10.1210/en.2013-1362] [PMID: 23832962]
Wake, D.J.; Walker, B.R. 11 beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Mol. Cell. Endocrinol., 2004, 215(1-2), 45-54.
[http://dx.doi.org/10.1016/j.mce.2003.11.015] [PMID: 15026174]
Hu, G.X.; Lin, H.; Lian, Q.Q.; Zhou, S.H.; Guo, J.; Zhou, H.Y.; Chu, Y.; Ge, R.S. Curcumin as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats. PLoS One, 2013, 8(3), e49976.
[http://dx.doi.org/10.1371/journal.pone.0049976] [PMID: 23533564]
Quadros, I.M.; Macedo, G.C.; Domingues, L.P.; Favoretto, C.A. An update on CRF mechanisms underlying alcohol use disorders and dependence. Front. Endocrinol. (Lausanne), 2016, 7, 134.
[http://dx.doi.org/10.3389/fendo.2016.00134] [PMID: 27818644]
Sanna, P.P.; Kawamura, T.; Chen, J.; Koob, G.F.; Roberts, A.J.; Vendruscolo, L.F.; Repunte-Canonigo, V. 11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse. Transl. Psychiatry, 2016, 6, e760.
[http://dx.doi.org/10.1038/tp.2016.13] [PMID: 26978742]
Wirth, M.M. Hormones, stress, and cognition: The effects of glucocorticoids and oxytocin on memory. Adapt. Human Behav. Physiol., 2015, 1(2), 177-201.
[http://dx.doi.org/10.1007/s40750-014-0010-4] [PMID: 25893159]
Nicolaides, N.C.; Kyratzi, E.; Lamprokostopoulou, A.; Chrousos, G.P.; Charmandari, E. Stress, the stress system and the role of glucocorticoids. Neuroimmunomodulation, 2015, 22(1-2), 6-19.
[http://dx.doi.org/10.1159/000362736] [PMID: 25227402]
de Kloet, E.R.; Joëls, M.; Holsboer, F. Stress and the brain: from adaptation to disease. Nat. Rev. Neurosci., 2005, 6(6), 463-475.
[http://dx.doi.org/10.1038/nrn1683] [PMID: 15891777]
Holmes, M.C.; Carter, R.N.; Noble, J.; Chitnis, S.; Dutia, A.; Paterson, J.M.; Mullins, J.J.; Seckl, J.R.; Yau, J.L. 11β-hydroxysteroid dehydrogenase type 1 expression is increased in the aged mouse hippocampus and parietal cortex and causes memory impairments. J. Neurosci., 2010, 30(20), 6916-6920.
[http://dx.doi.org/10.1523/JNEUROSCI.0731-10.2010] [PMID: 20484633]
Yau, J.L.; Noble, J.; Kenyon, C.J.; Hibberd, C.; Kotelevtsev, Y.; Mullins, J.J.; Seckl, J.R. Lack of tissue glucocorticoid reactivation in 11β -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Proc. Natl. Acad. Sci. USA, 2001, 98(8), 4716-4721.
[http://dx.doi.org/10.1073/pnas.071562698] [PMID: 11274359]
Sandeep, T.C.; Yau, J.L.; MacLullich, A.M.; Noble, J.; Deary, I.J.; Walker, B.R.; Seckl, J.R. 11β-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics. Proc. Natl. Acad. Sci. USA, 2004, 101(17), 6734-6739.
[http://dx.doi.org/10.1073/pnas.0306996101] [PMID: 15071189]
Sooy, K.; Noble, J.; McBride, A.; Binnie, M.; Yau, J.L.; Seckl, J.R.; Walker, B.R.; Webster, S.P. Cognitive and disease-modifying effects of 11β-hydroxysteroid dehydrogenase type 1 inhibition in male Tg2576 mice, a model of Alzheimer’s disease. Endocrinology, 2015, 156(12), 4592-4603.
[http://dx.doi.org/10.1210/en.2015-1395] [PMID: 26305888]
Rekka, E.A.; Kourounakis, A.P.; Kourounakis, P.N. Investigation of the effect of chamazulene on lipid peroxidation and free radical processes. Res. Commun. Mol. Pathol. Pharmacol., 1996, 92(3), 361-364.
[PMID: 8827832]
Kourounakis, A.P.; Rekka, E.A.; Kourounakis, P.N. Antioxidant activity of guaiazulene and protection against paracetamol hepatotoxicity in rats. J. Pharm. Pharmacol., 1997, 49(9), 938-942.
[http://dx.doi.org/10.1111/j.2042-7158.1997.tb06140.x] [PMID: 9306266]
Vinholes, J.; Gonçalves, P.; Martel, F.; Coimbra, M.A.; Rocha, S.M. Assessment of the antioxidant and antiproliferative effects of sesquiterpenic compounds in in vitro Caco-2 cell models. Food Chem., 2014, 156, 204-211.
[http://dx.doi.org/10.1016/j.foodchem. 2014.01.106] [PMID: 24629959]
Capuzzo, A.; Occhipinti, A.; Maffei, M.E. Antioxidant and radical scavenging activities of chamazulene. Nat. Prod. Res., 2014, 28(24), 2321-2323.
[http://dx.doi.org/10.1080/14786419.2014. 931393] [PMID: 24980540]
Rekka, E.; Chrysselis, M.; Siskou, I.; Kourounakis, A. Synthesis of new azulene derivatives and study of their effect on lipid peroxidation and lipoxygenase activity. Chem. Pharm. Bull. (Tokyo), 2002, 50(7), 904-907.
[http://dx.doi.org/10.1248/cpb.50.904] [PMID: 12130848]
Pratsinis, H.; Haroutounian, S.A. Synthesis and antioxidant activity of 3-substituted guaiazulene derivatives. Nat. Prod. Lett., 2002, 16(3), 201-205.
[http://dx.doi.org/10.1080/10575630290013585] [PMID: 12049221]
Cao, T.; Li, Y.; Yang, Z.; Yuan, M.; Li, Y.; Yang, H.; Feng, Y.; Yin, S. Synthesis and biological evaluation of 3,8-dimethyl-5-isopropylazulene derivatives as anti-gastric ulcer agent. Chem. Biol. Drug Des., 2016, 88(2), 264-271.
[http://dx.doi.org/10.1111/cbdd.12753] [PMID: 26938488]
Brewer, C.T.; Chen, T. PXR variants: the impact on drug metabolism and therapeutic responses. Acta Pharm. Sin. B, 2016, 6(5), 441-449.
[http://dx.doi.org/10.1016/j.apsb.2016.07.002] [PMID: 27709012]
Kourounakis, P.N.; Rekka, E. Structural considerations of the 16-cyano and related pregnenolones on their drug metabolic inducing activity. Eur. J. Med. Chem., 1990, 25, 701-704.
[http://dx.doi.org/ 10.1016/0223-5234(90)90136-Q]
Rekka, E.A.; Kourounakis, P.N. An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers. Eur. J. Drug Metab. Pharmacokinet., 1996, 21(1), 7-11.
[http://dx.doi.org/10.1007/BF03190271] [PMID: 8839671]
Francis, G.A.; Fayard, E.; Picard, F.; Auwerx, J. Nuclear receptors and the control of metabolism. Annu. Rev. Physiol., 2003, 65, 261-311.
[http://dx.doi.org/10.1146/annurev.physiol.65.092101.142528] [PMID: 12518001]
Ma, Y.; Liu, D. Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice. PLoS One, 2012, 7(6), e38734.
[http://dx.doi.org/10.1371/journal.pone.0038734] [PMID: 22723881]
Estabrook, R.W. A passion for P450s (rememberances of the early history of research on cytochrome P450). Drug Metab. Dispos., 2003, 31(12), 1461-1473.
[http://dx.doi.org/10.1124/dmd.31.12.1461] [PMID: 14625342]
Lewis, D.F.; Ito, Y. Human CYPs involved in drug metabolism: structures, substrates and binding affinities. Expert Opin. Drug Metab. Toxicol., 2010, 6(6), 661-674.
[http://dx.doi.org/10.1517/17425251003674380] [PMID: 20402561]
Parikh, A.; Gillam, E.M.; Guengerich, F.P. Drug metabolism by Escherichia coli expressing human cytochromes P450. Nat. Biotechnol., 1997, 15(8), 784-788.
[http://dx.doi.org/10.1038/nbt0897-784] [PMID: 9255795]
Vail, R.B.; Homann, M.J.; Hanna, I.; Zaks, A. Preparative synthesis of drug metabolites using human cytochrome P450s 3A4, 2C9 and 1A2 with NADPH-P450 reductase expressed in Escherichia coli. J. Ind. Microbiol. Biotechnol., 2005, 32(2), 67-74.
[http://dx.doi.org/10.1007/s10295-004-0202-1] [PMID: 15739102]
Szczebara, F.M.; Chandelier, C.; Villeret, C.; Masurel, A.; Bourot, S.; Duport, C.; Blanchard, S.; Groisillier, A.; Testet, E.; Costaglioli, P.; Cauet, G.; Degryse, E.; Balbuena, D.; Winter, J.; Achstetter, T.; Spagnoli, R.; Pompon, D.; Dumas, B. Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat. Biotechnol., 2003, 21(2), 143-149.
[http://dx.doi.org/10.1038/nbt775] [PMID: 12514739]
Behrendorff, J.B.; Gillam, E.M. Prospects for applying synthetic biology to toxicology: Future opportunities and current limitations for the re-purposing of cytochrome P450 systems. Chem. Res. Toxicol., 2017, 30(1), 453-468.
[http://dx.doi.org/10.1021/acs.chemrestox.6b00396] [PMID: 27957859]

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