Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases

Drug Metabolism and Disposition

Volumn 32, Issue 6, 2004, Pages 587-594

  Sridar, Chitra ^a   Goosen, Theunis C ^b   Kent, Ute M ^a   Williams, J Andrew ^b   Hollenberg, Paul F ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7 BENZYLOXY 4 (TRIFLUOROMETHYL)COUMARIN; 7 HYDROXY 4 (TRIFLUOROMETHYL)COUMARIN; COUMARIN DERIVATIVE; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; GLUCURONOSYLTRANSFERASE; HEME; SILIBININ; TESTOSTERONE; UNCLASSIFIED DRUG;

ARTICLE; DEBENZYLATION; DIALYSIS; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG STRUCTURE; ENZYME INHIBITION; GEL FILTRATION; IC 50; PRIORITY JOURNAL; SILYBUM MARIANUM; TESTOSTERONE METABOLISM;

ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 ENZYME SYSTEM; GLUCURONOSYLTRANSFERASE; HEME; KINETICS; NADP; PLANT EXTRACTS; RECOMBINANT PROTEINS; SILYMARIN; TESTOSTERONE;

CIRSIUM; SILYBUM MARIANUM;

EID: 2442649042     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.32.6.587     Document Type: Article

References (39)

1. Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, Bocker RH, Beckurts KT, Lang W, Hunz M, and Fuhr U (2000) Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 86:250-256.
2. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, et al.; Pharmaceutical Research and Manufacturers of America Drug Metabolism and Clinical Pharmacology Technical Working Group (2003) The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos 31:815-832.
3. Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism and nutritional significance. Nutr Rev 56:317-333.
4. Carini R, Comoglio A, Albano E, and Poli G (1992) Lipid peroxidation and irreversible damage in the rat hepatocyte model. Protection by the silybin-phospholipid complex IdB 1016. Biochem Pharmacol 43:2111-2115.
5. Dehmlow C, Erhard J, and de Groot H (1996) Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 23:749-754.
6. Dwyer J (1995) Overview: dietary approaches for reducing cardiovascular disease risks. J Nutr 125:656S-665S.
7. Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, and Schneider B (1989) Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9:105-113.
8. Fisher MB, Paine MF, Strelevitz TJ, and Wrighton SA (2001) The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metab Rev 33:273-297.
9. Flora K, Hahn M, Rosen H, and Benner K (1998) Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 93:139-143.
10. Fuhr U (1998) Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance. Drug Saf 18:251-272.
11. Gerhauser C, Klimo K, Heiss E, Neumann I, Gamal-Eldeen A, Knauft J, Liu GY, Sitthimonchai S, and Frank N (2003) Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat Res 523-524:163-172.
12. Gillam EM, Baba T, Kim BR, Ohmori S, and Guengerich FP (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123-131.
13. Guengerich FP (1991) Reactions and significance of cytochrome P-450 enzymes. J Biol Chem 266:10019-10022.
14. Hanna IH, Reed JR, Guengerich FP, and Hollenberg PF (2000) Expression of human cytochrome P450 2B6 in Escherichia coli: characterization of catalytic activity and expression levels in human liver. Arch Biochem Biophys 376:206-216.
15. Hanna IH, Teiber JF, Kokones KL, and Hollenberg PF (1998) Role of the alanine at position 363 of cytochrome P450 2B2 in influencing the NADPH- and hydroperoxide-supported activities. Arch Biochem Biophys 350:324-332.
16. Hertog MGL, Hollman PCH, and van de Putte B (1993) Content of potentially anticarcinogenic flavonoids of tea infusions, wines and fruit juices. J Agric Food Chem 41:1242-1246.
17. Hruby K, Csomos G, Fuhrmann M, and Thaler H (1983) Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2:183-195.
18. Iyer L, Hall D, Das S, Mortell MA, Ramirez J, Kim S, Di Rienzo A, and Ratain MJ (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism. Clin Pharmacol Ther 65:576-582.
19. Koop DR (1990) Inhibition of ethanol-inducible cytochrome P45011E1 by 3-amino-1,2,4-triazole. Chem Res Toxicol 3:377-383.
20. Liston HL, Markowitz JS, and DeVane CL (2001) Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol 21:500-515.
21. Lu P, Lin Y, Rodrigues AD, Rushmore TH, Baillie TA, and Shou M (2001) Testosterone, 7-benzyloxyquinoline and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4. Drug Metab Dispos 29:1473-1479.
22. Miguez MP, Anundi I, Sainz-Pardo LA, and Lindros KO (1994) Hepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1. Chem Biol Interact 91:51-63.
23. 4-induced liver cirrhosis by silymarin. Fundam Clin Pharmacol 3:183-191.
24. Muriel P, Garciapina T, Perez-Alvarez V, and Mourelle M (1992) Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol 12:439-442.
25. Salmi HA and Sarna S (1982) Effect of silymarin on chemical, functional and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17:517-521.
26. Sandhu P, Baba T, and Guengerich FP (1993) Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli: purification and reconstitution of catalytic activity. Arch Biochem Biophys 306:443-450.
27. Schrag ML and Wienkers LC (2001) Triazolam substrate inhibition: evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metab Dispos 29:70-75.
28. Siess MH, Leclerc J, Canivenc-Lavier MC, Rat P, and Suschetet M (1995) Heterogenous effects of natural flavonoids on monooxygenase activities in human and rat liver microsomes. Toxicol Appl Pharmacol 130:73-78.
29. Singh RP and Agarwal R (2002) Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal 4:655-663.
30. Sonnenbichler J, Goldberg M, Hane L, Madubunyi I, Vogl S, and Zetl I (1986) Stimulatory effect of Silibinin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malign cell lines. Biochem Pharmacol 35:538-541.
31. Sweetman S (2002) Martindale: The Complete Drug Reference, 33rd ed. Pharmaceutical Press, London.
32. USP (2002) The United States Pharmacopeia and The National Formulary. United States Pharmacopeial Convention, Rockville, MD.
33. Valenzuela A, Bustamante JC, Videla C, and Guerra R (1989) Effect of silybin dihemisuccinate on the ethanol metabolizing systems of the rat liver. Cell Biochem Funct 7:173-178.
34. Valenzuela A, Guerra R, and Videla LA (1986) Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med 6:438-440.
35. Valenzuela A, Lagos C, Schmidt K, and Videla LA (1985) Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem Pharmacol 34:2209-2212.
36. Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, and Strom SC (2000) Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28:1270-1273.
37. Vogel G, Tuchweber B, Trost W, and Mengs U (1984) Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol 73:355-362.
38. Weyhenmeyer R, Mascher H, and Birkmayer J (1992) Study on dose-linearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay. Int J Clin Pharmacol Ther Toxicol 30:134-138.
39. Yanev S, Kent UM, Pandova B, and Hollenberg PF (1999) Selective mechanism-based inactivation of cytochromes P-450 2B1 and P-450 2B6 by a series of xanthates. Drug Metab Dispos 27:600-604.