Possible protective role of pregnenolone-16α-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis

European Journal of Pharmacology

Volumn 636, Issue 1-3, 2010, Pages 145-154

  Miyata, Masaaki ^a   Nomoto, Masahiro ^a,b   Sotodate, Fumiaki ^a   Mizuki, Tomohiro ^a   Hori, Wataru ^a   Nagayasu, Miho ^a   Yokokawa, Shinya ^c   Ninomiya, Shin ichi ^c   Yamazoe, Yasushi ^a  

^a TOHOKU UNIVERSITY   (Japan)

^b MEIJI SEIKA KAISHA LTD   (Japan)

^c SEKISUI CHEMICAL CO LTD   (Japan)

Author keywords

Hepatotoxicity; Lipogenesis; Lithocholic acid; PCN; Phospholipid; PXR

Indexed keywords

16ALPHA CYANOPREGNENOLONE; ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; BILE ACID; FATTY ACID DERIVATIVE; LITHOCHOLIC ACID; MESSENGER RNA; PHOSPHATIDYLCHOLINE; PHOSPHOLIPID; TRIACYLGLYCEROL;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; FEMALE; LIPID METABOLISM; LIPOGENESIS; LIVER PROTECTION; LIVER TOXICITY; MOUSE; NONHUMAN; PHOSPHOLIPID SYNTHESIS; PRIORITY JOURNAL;

ANIMALS; BILIARY TRACT; BIOLOGICAL MARKERS; FATTY ACIDS; FEMALE; GENE EXPRESSION PROFILING; HEPATOCYTES; LIPOGENESIS; LITHOCHOLIC ACID; LIVER; LIVER DISEASES; MICE; MICE, INBRED C57BL; PHOSPHATIDYLCHOLINES; PREGNENOLONE CARBONITRILE; TIME FACTORS;

EID: 77952673972     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2010.03.022     Document Type: Article

References (39)

1. Dolinsky V.W., Gilham D., Alam M., Vance D.E., Lehner R. Triacylglycerol hydrolase: role in intracellular lipid metabolism. Cell. Mol. Life Sci. 2004, 61:1633-1651.
2. Fickert P., Fuchsbichler A., Marschall H.U., Wagner M., Zollner G., Krause R., Zatloukal K., Jaeschke H., Denk H., Trauner M. Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice. Am. J. Pathol. 2006, 168:410-422.
3. Futter C.E., White I.J. Annexins and endocytosis. Traffic 2007, 8:951-958.
4. Hofmann A.F. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab. Rev. 2004, 36:703-722.
5. Kanno K., Wu M.K., Scapa E.F., Roderick S.L., Cohen D.E. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim. Biophys. Acta 2007, 1771:654-662.
6. Kitada H., Miyata M., Nakamura T., Tozawa A., Honma W., Shimada M., Nagata K., Sinal C.J., Guo G.L., Gonzalez F.J., Yamazoe Y. Protective role of hydroxysteroid sulfotransferase in lithocholic acid-induced liver toxicity. J. Biol. Chem. 2003, 278:17838-17844.
7. Kliewer S.A., Moore J.T., Wade L., Staudinger J.L., Watson M.A., Jones S.A., McKee D.D., Oliver B.B., Willson T.M., Zetterstrom R.H., Perlmann T., Lehmann J.M. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998, 92:73-82.
8. Kourounakis P., Szabo S., Selye H. Effect of pregnenolone-16alpha-constitutive androstane receptorbonitrile on the rat liver. Arzneimittelforschung 1976, 26:74-75.
9. Minahk C., Kim K.W., Nelson R., Trigatti B., Lehner R., Vance D.E. Conversion of low density lipoprotein-associated phosphatidylcholine to triacylglycerol by primary hepatocytes. J. Biol. Chem. 2008, 283:6449-6458.
10. Miyata M., Tozawa A., Otsuka H., Nakamura T., Nagata K., Gonzalez F.J., Yamazoe Y. Role of farnesoid X receptor in the enhancement of canalicular bile acid output and excretion of unconjugated bile acids: a mechanism for protection against cholic acid-induced liver toxicity. J. Pharmacol. Exp. Ther. 2005, 312:759-766.
11. Miyata M., Watase H., Hori W., Shimada M., Nagata K., Gonzalez F.J., Yamazoe Y. Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity. Xenobiotica 2006, 36:631-644.
12. Nakamura K., Moore R., Negishi M., Sueyoshi T. Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. J. Biol. Chem. 2007, 282:9768-9776.
13. Nomoto M., Miyata M., Shimada M., Yoshinari K., Gonzalez F.J., Shibasaki S., Kurosawa T., Shindo Y., Yamazoe Y. ME3738 protects against lithocholic acid-induced hepatotoxicity, which is associated with enhancement of biliary bile acid and cholesterol output. Eur. J. Pharmacol. 2007, 574:192-200.
14. Okazaki H., Igarashi M., Nishi M., Tajima M., Sekiya M., Okazaki S., Yahagi N., Ohashi K., Tsukamoto K., Amemiya-Kudo M., Matsuzaka T., Shimano H., Yamada N., Aoki J., Morikawa R., Takanezawa Y., Arai H., Nagai R., Kadowaki T., Osuga J., Ishibashi S. Identification of a novel member of the constitutive androstane receptor boxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis. Diabetes 2006, 55:2091-2097.
15. Oude Elferink R.P., Paulusma C.C. Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch. 2007, 453:601-610.
16. Oude Elferink R.P., Paulusma C.C., Groen A.K. Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology 2006, 130:908-925.
17. Owen B.M., Milona A., van Mil S., Clements P., Holder J., Boudjelal M., Cairns W., Parker M., White R., Williamson C. Intestinal detoxification limits the activation of hepatic pregnane X receptor by lithocholic acid. Drug Metab. Dispos. 2010, 38:143-149.
18. Puglielli L., Amigo L., Arrese M., Nunez L., Rigotti A., Garrido J., Gonzalez S., Mingrone G., Greco A.V., Accatino L., et al. Protective role of biliary cholesterol and phospholipid lamellae against bile acid-induced cell damage. Gastroenterology 1994, 107:244-254.
19. Radenne A., Akpa M., Martel C., Sawadogo S., Mauvoisin D., Mounier C. Hepatic regulation of fatty acid synthase by insulin and T3: evidence for T3 genomic and nongenomic actions. Am. J. Physiol. Endocrinol. Metab. 2008, 295:E884-E894.
20. Repa J.J., Liang G., Ou J., Bashmakov Y., Lobaccaro J.M., Shimomura I., Shan B., Brown M.S., Goldstein J.L., Mangelsdorf D.J. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000, 14:2819-2830.
21. Robichaud J.C., van der Veen J.N., Yao Z., Trigatti B., Vance D.E. Hepatic uptake and metabolism of phosphatidylcholine associated with high density lipoproteins. Biochim. Biophys. Acta 2009, 1790:538-551.
22. Sahu S.K., Gummadi S.N., Manoj N., Aradhyam G.K. Phospholipid scramblases: an overview. Arch. Biochem. Biophys. 2007, 462:103-114.
23. Saini S.P., Sonoda J., Xu L., Toma D., Uppal H., Mu Y., Ren S., Moore D.D., Evans R.M., Xie W. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol. Pharmacol. 2004, 65:292-300.
24. Schultz J.R., Tu H., Luk A., Repa J.J., Medina J.C., Li L., Schwendner S., Wang S., Thoolen M., Mangelsdorf D.J., Lustig K.D., Shan B. Role of LXRs in control of lipogenesis. Genes Dev. 2000, 14:2831-2838.
25. Selye H. Prevention by catatoxic steroids of lithocholic acid-induced biliary concrements in the rat. Proc. Soc. Exp. Biol. Med. 1972, 141:555-558.
26. Selye H., Szabo S., Kourounakis P. Protection by catatoxic steroids, phenobarbital and diphenylhydantoin against methaqualone intoxication. Steroids. Lipids Res. 1972, 3:156-159.
27. Sinha Roy S., Mukherjee S., Kabir S., Rajaratnam V., Smith M., Das S.K. Inhibition of choline phosphotransferase activity in lung injury induced by 2-chloroethyl ethyl sulfide, a mustard analog. J. Biochem. Mol. Toxicol. 2005, 19:289-297.
28. Sonoda J., Xie W., Rosenfeld J.M., Barwick J.L., Guzelian P.S., Evans R.M. Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc. Natl. Acad. Sci. U. S. A. 2002, 99:13801-13806.
29. Staudinger J.L., Goodwin B., Jones S.A., Hawkins-Brown D., MacKenzie K.I., LaTour A., Liu Y., Klaassen C.D., Brown K.K., Reinhard J., Willson T.M., Koller B.H., Kliewer S.A. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:3369-3374.
30. Trauner M., Boyer J.L. Bile salt transporters: molecular characterization, function, and regulation. Physiol. Rev. 2003, 83:633-671.
31. Trauner M., Fickert P., Wagner M. MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes. Semin. Liver Dis. 2007, 27:77-98.
32. Tsuboi K., Tazuma S., Nishioka T., Chayama K. Partial characterization of cytoprotective mechanisms of lecithin against bile salt-induced bile duct damage. J. Gastroenterol. 2004, 39:955-960.
33. Uppal H., Toma D., Saini S.P., Ren S., Jones T.J., Xie W. Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice. Hepatology 2005, 41:168-176.
34. Uppal H., Saini S.P., Moschetta A., Mu Y., Zhou J., Gong H., Zhai Y., Ren S., Michalopoulos G.K., Mangelsdorf D.J., Xie W. Activation of LXRs prevents bile acid toxicity and cholestasis in female mice. Hepatology 2007, 45:422-432.
35. Wu M.K., Cohen D.E. Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins. Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 289:G1067-G1074.
36. Xie W., Radominska-Pandya A., Shi Y., Simon C.M., Nelson M.C., Ong E.S., Waxman D.J., Evans R.M. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:3375-3380.
37. Yousef I.M., Bouchard G., Tuchweber B., Plaa G.L. Monohydroxy bile acid induced cholestasis: role of biotransformation. Drug Metab. Rev. 1997, 29:167-181.
38. Zhang J., Huang W., Qatanani M., Evans R.M., Moore D.D. The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. J. Biol. Chem. 2004, 279:49517-49522.
39. Zhou J., Zhai Y., Mu Y., Gong H., Uppal H., Toma D., Ren S., Evans R.M., Xie W. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J. Biol. Chem. 2006, 281:15013-15020.