Hepatic sinusoidal-obstruction syndrome: Toxicity of pyrrolizidine alkaloids

Journal of Hepatology

Volumn 39, Issue 3, 2003, Pages 437-446

  Chojkier, Mario ^a  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM CHANNEL BLOCKING AGENT; CLOTRIMAZOLE; CORTICOSTEROID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYPERICUM PERFORATUM EXTRACT; KETOCONAZOLE; MACROLIDE; MIDAZOLAM; PHENOBARBITAL; PREGNANE X RECEPTOR; PYRROLIZIDINE ALKALOID; RIFAMPICIN; RITONAVIR; SILDENAFIL; TAMOXIFEN;

CARCINOGENESIS; DRUG BIOAVAILABILITY; DRUG METABOLISM; DRUG SAFETY; HEPATIC SINUSOIDAL OBSTRUCTION SYNDROME; HERBAL MEDICINE; HUMAN; LIVER INJURY; LIVER METABOLISM; LIVER SINUSOID; LIVER TOXICITY; LUNG TOXICITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SYNDROME;

EID: 0042830247     PISSN: 01688278     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0168-8278(03)00231-9     Document Type: Review

References (181)

1. Poreddy V, DeLeve LD. Hepatic circulatory diseases associated with chronic myeloid disorders. Clin Liver Dis 2002;6:909-31.
2. Ober D, Hartmann T. Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase. Proc Natl Acad Sci USA 1999;96:14777-82.
3. Huxtable RJ. Herbal teas and toxins: novel aspects of pyrrolizidine poisoning in the United States. Perspect Biol Med 1980;24:1-14.
4. Stegelmeier BL, Edgar JA, Colegate SM, Gardner DR, Schoch TK, Coulombe RA, et al. Pyrrolizidine alkaloid plants, metabolism and toxicity. J Nat Toxins 1999;8:95-116.
5. International Programme on Chemical Safety, International programme on chemical safety. Geneva: World Health Organization; 1988. p. 1-232.
6. Huxtable RJ. Human health implications of pyrrolizidine alkaloids and herbs containing them. In: Cheeke PR, editor. Toxicants of plant origins. Boca Raton, FL: CRC Press, Inc;2001. p. 41-79.
7. Ridker PM, McDermott WV. Comfrey herb tea and hepatic venoocclusive disease. Lancet 1989;1:657-8.
8. Girard M, Fillion J, Kindack D, Awang DVC. Investigation of echimidine content of commercial comfrey preparations. Report 89/I. 1989. Bureau of Drug Research, Canada.
9. Hartmann T, Witte L. Alkaloids: chemical and biological perspectives. In: Pelletier SW, editor. Oxford: Pergamon;1995. p. 155-233.
10. IARC. Effects on man. In Pyrrolizidine alkaloids. 1988. pp. 179-226 [International Programme on Chemical Safety, World Health Organization, Geneva].
11. Cheeke PR. A review of the functional and evolutionary roles of the liver in the detoxification of poisonous plants, with special reference to pyrrolizidine alkaloids. Vet Hum Toxicol 1994;36:240-7.
12. Yeong ML, Wakefield SJ, Ford HC. Hepatocyte membrane injury and bleb formation following low dose comfrey toxicity in rats. Int J Exp Path 1993;74:211-7.
13. Couet CE, Crews C, Hanley AB. Analysis, separation, and bioassay of pyrrolizidine alkaloids from comfrey (symphytum officinale). Nat Toxins 1996;4:163-7.
14. Yeong ML, Clark SP, Waring JM, Wilson RD, Wakefield SJ. The effects of comfrey derived pyrrolizidine alkaloids on rat liver. Pathology 1991;23:35-8.
15. Hartmann T, Ehmke A, Eilert U, von Borstel K, Theuring C. Sites of synthesis, translocation and accumulation of pyrrolizidine alkaloid N-oxides in Senecio vulgaris L. Planta 1989;177:98-107.
16. Roitman JN. Comfrey and liver damage. Lancet 1981;1:944.
17. Mattocks AR. Toxic pyrrolizidine alkaloids in comfrey. Lancet 1980;2:1136-7.
18. Hartmann T. Chemical ecology of pyrrolizidine alkaloids. Planta 1999;207:483-95.
19. Mattocks AR. Toxicity of pyrrolizidine alkaloids. Nature 1968;217:723-8.
20. Hartmann T, Sander H, Adolph R-D, Toppel G. Metabolic links between the biosynthesis of pyrrolizidine alkaloids and polyamines in root cultures of Senecio vulgaris. Planta 1988;175:82-90.
21. Fujiwara K, Nagoshi S. Biological activity of growth factors in vivo. In: Strain A, Diehl AM, editors. Liver growth and repair. London: Chapman & Hall; 1998. p. 163-82.
22. Sato Y, Fujiwara K. Compensatory route of spermidine acetylation and oxidation can supply sufficient putrescine for hepatic DNA synthesis at an early stage after partial hepatectomy in diaminopropane-treated rats. J Biochem 1988;104:98-101.
23. Sato Y, Fujiwara K, Ogata I. Additive stimulation of hepatic putrescine production by glucagon and insulin after partial hepatectomy in rats. Life Sci 1989;45:77-83.
24. Böttcher F, Adolph R-D, Hartmann T. Homospermidine synthase, the first pathway-specific enzyme in pyrrolizidine alkaloid biosynthesis. Phytochemistry 1993;32:679-89.
25. Böttcher F, Ober D, Hartmann T. Biosynthesis of pyrrolizidine alkaloids: putrescine and spermidine are essential substrates of enzymatic homospermidine formulation. Can J Chem 1994;72:80-5.
26. Smit-McBride Z, Dever TE, Hershey JW, Merrick WC. Sequence determination and cDNA cloning of eukaryotic initiation factor 4D, the hypusine-containing protein. J Biol Chem 1989;264:1578-83.
27. Krishna RG, Wold F. Post-translational modification of proteins. Adv Enzymol 1993;67:265-98.
28. Kang HA, Hershey JW. Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae. J Biol Chem 1994;269:3934-40.
29. Park MH, Wolff EC, Folk JK Hypusine: its post-translational formation in eukaryotic initiation factor 5A and its potential role in cellular regulation. Biofactors 1993;4:95-104.
30. Ruhl M, Himmelspach M, Bahr GM, Hammerschmid F, Jaksche H, Wolff B, et al. Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans- activation. J Cell Biol 1993;123:1309-20.
31. Czaja MJ. Liver regeneration following hepatic injury. In: Strain A, Diehl AM, editors. Liver growth and repair. London: Chapman and Hall; 1998. p. 28-49.
32. Lipton SA, Choi Y-B, Pan Z-H, Lei SZ, Chen H-SV, Sucher NJ, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 1993;364:626-32.
33. Buck M, Zhang L, Hunter T, Chojkier M. Nuclear export of phosphorylated C/EBPβ mediates the inhibition of albumin expression by TNFα. EMBO J 2001;20:6712-23.
34. Buck M, Chojkier M. Muscle wasting and dedifferentiafion induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J 1996;15:1753-65.
35. Majano PL, Garciá-Monzón C, López-Cabrera M, Lara-Pezzi E, Fernández-Ruiz E, Garcia-Iglesias C, et al. Inducible nitric oxide synthase expression in chronic viral hepatitis. J Clin Invest 1998;101:1343-52.
36. Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 2002;35:478-91.
37. Huxtable RJ, Luthy J, Zweifel U. Toxicity of comfrey-pepsin preparations. N Engl J Med 1986;315:1095.
38. Duke JA. Handbook of medicinal herbs. Boca Raton: CRC Press; 1985.
39. Bianchini F, Corbetta F. Health plants of the world: atlas of medicinal plants. New York: Newsweek Books; 1979.
40. Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health-Syst Pharm 1999;56:125-41.
41. Huxtable RJ. The myth of beneficent nature: the risks of herbal preparations. Ann Intern Med 1992;117:165-6.
42. Winship K. Toxicity of comfrey. Adverse Drug React Toxicol Rev 1991;10:47-59.
43. Larrey D, Pageaux GP. Hepatotoxicity of herbal remedies and mushrooms. Semin Liv Dis 1995;15:183-8.
44. Mattocks AR. Hepatotoxic effects due to pyrrolizidine alkaloid N-oxides. Xenobiotica 1971;1:563-5.
45. Mattocks AR. Spectrophotometric determination of pyrrolizidine alkaloids - some improvements. Anal Chem 1968:40:1749-50.
46. Mattocks AR. The occurrence and analysis of pyrrolizidine alkaloid N-oxides. Xenobiotica 1971;1:451-3.
47. Mattocks AR, White INH. The conversion of pyrrolizidine alkaloids to dihydropyrrolizine derivatives by rat-liver microsomes in vitro. Chem Biol Interact 1971;3:383.
48. Huan JY, Miranda CL, Buhler DR, Cheeke PR. Species differences in the hepatic microsomal enzyme metabolism of the pyrrolizidine alkaloids. Toxicol Lett 1998;99:127-37.
49. 32P-postlabeling/HPLC method for detection of dehydroretronecine-derived DNA adducts in vivo and in vitro. Chem Res Toxicol 2001;14:91-100.
50. Stickel F, Seitz HK. The efficacy and safety of comfrey. Public Health Nutrition 2000;3:501-8.
51. Mattocks AR. Chemistry and toxicology of pyrrolizidine alkaloids. London: Academic Press; 1986.
52. Jago MV. Factors affecting the chronic hepatotoxicity of pyrrolizidine alkaloids. J Pathol 1971;105:1-11.
53. Tuchweber B, Kovacs K, Jago MV, Beaulieu T. Effect of steroidal and non-steroidal microsomal enzyme inducers on the hepatotoxicity of pyrrolizidine alkaloids in rats. Res Commun Chem Pathol Pharmacol 1974;7:459-80.
54. Brauchli J, Luthy J, Zweifel U, Schlatter C. Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorption in rats. Experientia 1982;38:1085-7.
55. Kim H-Y, Stermitz FR, Coulombe Jr RA. Pyrrolizidine alkaloid-induced DNA-protein cross-links. Carcinogenesis 1995;16:2691-7.
56. Prakash AS, Pereira TN, Reilly PE, Seawright AA. Pyrrolizidine alkaloids in human diet. Mutat Res 1999;15:53-67.
57. Houglum K, Filip M, Witztum JL, Chojkier M. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J Clin Invest 1990;86:1991-8.
58. 1(I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload. Am J Physiol 1994;267:G908-13.
59. Niemela O, Parkkila S, Juvonen RO, Viitala K, Gelboin HV, Pasanen M. Cytochromes P450 2A6, 2E1, and 3A and production of protein-aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases. J Hepatol 2000;33:893-901.
60. Holstege A, Bedossa P, Poynard T, Kollinger M, Chaput JC, Houglum K. et al. Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and non-alcoholic patients: localization and association with progression of liver fibrosis. Hepatology 1994;19:367-74.
61. Brenner DA, Chojkier M. Acetaldehyde increases collagen gene transcription in cultured human fibroblasts. J Biol Chem 1987;262:17690-5.
62. Gura T. Can SNPs deliver on susceptibility genes? Science 2001;293:593-5.
63. Kuehl P, Zhang L, Lin Y, Lamba J, Assem M, Schuetz J, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001;27:383-91.
64. Eichelbaum M, Burk O. CYP3A genetics in drug metabolism. Nat Med 2001;7:285-7.
65. Hustert E, Haberl M, Burk O, Wolbold R, He YQ, Klein K, et al. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 2001;11:773-9.
66. Joannard F, Galisteo M, Corcos L, Guillouzo A, Lagadic-Gossmann D. Regulation of phenobarbital-induction of CYP2B and CYP3A genes in rat cultured hepatocytes: involvement of several serine/threonine protein kinases and phosphatases. Cell Biol Toxicol 2000;16:325-37.
67. Quattrochi LC, Guzelian PS. CYP3A regulation: from pharmacology to nuclear receptors. Drug Metab Dispos 2001;29:615-22.
68. Weber A, Kaplan M, Chughtai SA, Cohn LA, Smith AL, Unadkat JD. CYP3A inductive potential of the rifamycins, rifabutin and rifampin, in the rabbit. Biopharm Drug Dispos 2001;22:157-68.
69. Hoen PA, Bijsterbosch MK, van Berkel TJ, Vermeulen NP, Commandeur JN. Midazolam is a phenobarbital-like cytochrome P450 inducer in rats. J Pharmacol Exp Ther 2001;299:921-7.
70. Pascussi JM, Drocourt L, Gerbal-Chaloin S, Fabre JM, Maurel P, Vilarem MJ. Dual effect of dexamethasone on CYP3A4 gene expression in human hepatocytes. Eur J Biochem 2001;268:6346-58.
71. Vogel G. Pharmacology. How the body's 'garbage disposal' may inactivate drugs. Science 2001;291:35-7.
72. Vogel G, Pharmacology A. worrisome side effect of an antianxiety remedy. Science 2001;291:37.
73. Wargovich MJ, Woods C, Hollis DM, Zander ME. Herbals, cancer prevention and health. J Nutr 2001;131:3034S-6S.
74. Drocourt L, Pascussi JM, Assenat E, Fabre JM, Maurel P, Vilarem MJ. Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab Dispos 2001;29:1325-31.
75. Schmidt LE, Olsen AK, Stentoft K, Rasmussen A, Kirkegaard P, Dalhoff K. Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients. Clin Pharmacol Ther 2001;70:446-54.
76. Kuroha M, Azumano A, Kuze Y, Shimoda M, Kokue E. Effect of multiple dosing of ketoconazole on pharmacokinetics of midazolam, a cytochrome P-450 3A substrate in beagle dogs. Drug Metab Dispos 2002;30:63-8.
77. Kumar GN, Dykstra J, Roberts EM, Jayanti VK, Hickman D, Uchic J, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: a positive drug-drug interaction. Drug Metab Dispos 1999;27:902-8.
78. Mousa O, Brater DC, Sunblad KJ, Hall SD. Fas and Fas-ligand expression in human pancreatic cancer. Clin Pharmacol Ther 2000;67:267-74.
79. Zusman RM, Morales A, Glasser DB, Osterloh IH. Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 1999;83:35C-44C.
80. Mattocks AR. Acute hepatotoxicity and pyrrolic metabolites in rats dosed with pyrrolizidine alkaloids. Chem Biol Interact 1972;5:227-42.
81. Mattocks AR, White INH. Toxic effects and pyrrolic metabolites in the liver of young rats given the pyrrolizidine alkaloid retrorsine. Chem Biol Interact 1973;6:297-306.
82. Gorski JC, Wang Z, Haehner-Daniels BD, Wrighton SA, Hall SD. The effect of hormone replacement therapy of CYP3A activity. Clin Pharmacol Ther 2000;68:412-7.
83. Mueller CR, Maire P, Schibler U. DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell 1990;61:279-91.
84. Ourlin JC, Jounaidi Y, Maurel P, Vilarem MJ. Role of the liver-enriched transcription factors C/EBP alpha and DBP in the expression of human CYP3A4 and CYP3A7. J Hepatol 1997;26:54-62.
85. Lavery DJ, Schibler U. Circadian transcription of the cholesterol 7 hydroxylase gene may involve the liver-enriched bZIP protein DBP. Genes Dev 1993;7:1871-84.
86. Wuarin J, Schibler U. Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell 1990;63:1257-66.
87. Bastien MC, Leblond F, Pichette V, Villeneuve JP. Differential alteration of cytochrome P450 isoenzymes in two experimental models of cirrhosis. Can J Physiol Pharmacol 2000;78:912-9.
88. Mazzei T, Surrenti C, Novelli A, Biagini MR, Fallani S, Cassetta MI, et al. Pharmacokinetics of dirithromycin in patients with mild or moderate cirrhosis. Antimicrob Agents Chemother 1999;43:1556-9.
89. Barre J, Mallat A, Rosenbaum J, Deforges L, Houin G, Dhumeaux D, et al. Pharmacokinetics of erythromycin in patients with severe cirrhosis. Respective influence of decreased serum binding and impaired liver metabolic capacity. Br J Clin Pharmacol 1987;23:753-7.
90. Poli V, Ciliberto G. Transcriptional regulation of acute phase genes by IL-6 and related cytokines. In: Tronche F, Yaniv M, editors. Liver gene expression. Austin: R.G. Landes Co; 1994. p. 131-51.
91. Akira S, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL and TNF). FASEB J 1990;4:2860-7.
92. Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, et al. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of IL-I. J Exp Med 1986;163:1433-50.
93. Gordon CJ, Coleman WB, Grisham JW. Induction of cytochrome P450 enzymes in the livers of rats treated with the pyrrolizidine alkaloid retrorsine. Exp Mol Pathol 2000;69:17-26.
94. Culvenor CCJ, Clarke M, Edgar JA. Structure and toxicity of the alkaloids of Russian comfrey (Symphytum X uplandicum Nyman), a medicinal herb and item of human diet. Experientia 1980;36(Fas. 4):377-502.
95. Chojkier M. Regulation of collagen gene expression. In: Strain A, Diehl A, editors. Liver growth and repair. London: Chapman & Hall; 1998. p. 430-50.
96. Wang X, Kanel GC, DeLeve LD. Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat. Hepatology 2000;31:428-34.
97. Chojkier M, Houglum K, Lee KS, Buck M. Long-and short-term D-α-tocopherol supplementation inhibits liver collagen α1(I) gene expression. Am J Physiol 1998;275:G1480-5.
98. Ankoma-Sey V, Friedman S. Hepatic stellate cells. In: Strain A, Diehl A, editors. Liver growth and repair. London: Chapman and Hall; 1998. p. 512-37.
99. 1(I) gene from a 5′ regulatory region. J Clin Invest 1994;94:808-14.
100. 1(I) gene in hepatic stellate cells and in skin and tendon fibroblasts. J Clin Invest 1995;96:2269-76.
101. Huxtable RJ. Activation and pulmonary toxicity of pyrrolizidine alkaloids. Pharmacol Ther 1990;47:371-89.
102. Mattocks AR, Driver E. Toxic actions of senaetnine, a new pyrrolizidine-type alkaloid, in rats. Toxicol Lett 1987;38:315-9.
103. Chojkier M, Fierer J. D-Galactosamine hepatotoxicity is associated with endotoxin-sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 1985;88:115-21.
104. Scholmerich J, DeLuca M, Chojkier M. Bioluminescence assays for bile acids in the detection and follow-up of experimental liver injury. Hepatology 1984;4:639-43.
105. Magee PN, Farber E. Toxic liver injury and carcinogenesis. Biochem J 1962;83:114-24.
106. Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998;282:2085-5088.
107. Galanos C, Freudenberg MA, Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci USA 1979;76:5939-43.
108. Freudenberg MA, Galanos C. Induction of tolerance to lipopolysaccharide (LPS)-D-galactosamine lethality by pretreatment with LPS in mediated by macrophages. Infect Immun 1988;56:1352-7.
109. Alcorn JM, Fierer J, Chojkier M. The acute-phase response protects mice from D-galactosamine sensitization to endotoxin and tumor necrosis factor-α. Hepatology 1992;15:122-9.
110. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M, et al. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 2000;25:187-91.
111. Yee SB, Kinser S, Hill DA, Barton CC, Hotchkiss JA, Harkema JR, et al. Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline. Toxicol Appl Pharmacol 2000;166:173-85.
112. Schoental R. Liver lesions in young rats suckled by mothers with the pyrrolizidine (senecio) alkaloids, lasiocarpine and retrorsine. J Path Bact 1959;77:485-95.
113. Noble JW, Crossley JB, Hill BD, Pierce RJ, McKenzie RA, Debritz M, et al. Pyrrolizidine alkaloidosis of cattle associated with Senecio lautus. Aust Vet J 1994;71:196-200.
114. Yan CC, Huxtable RJ. Quantitation of the hepatic release of metabolites of the pyrrolizidine alkaloid, monocrotaline. Toxicol Appl Pharmacol 1994;127:58-63.
115. Lamé MW, Jones AD, Wilson DW, Dunston SK, Segall HJ. Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells. J Biol Chem 2000;275:29091-9.
116. Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000;6:698-702.
117. Chen M-J, Chiang LY, Lai YL. Reactive oxygen species and substance P in monocrotaline-induced pulmonary hypertension. Toxicol Appl Pharmacol 2001;171:165-73.
118. Perazzo J, Eizayaga F, Romay S, Bengochea L, Pavese A, Lemberg A. An experimental model of liver damage and portal hypertension induced by a single dose of monocrotaline. Hepatogastroenterology 1999;46:432-5.
119. DeLeve LD, McCuskey RS, Wang X, Hu L, McCuskey MK, Epstein RB, et al. Characterization of a reproducible rat model of hepatic veno-occlusive disease. Hepatology 1999;29:1779-91.
120. Lyford CL, Vergara GG, Moeller DD. Hepatic veno-occlusive disease originating in Equador. Gastroenterology 1976;70:105-8.
121. McGee JO, Patrick RS, Wood CB, Blumgart LH. A case of venoocclusive disease of the liver in Britain associated with herbal tea consumption. J Clin Path 1976;29:788-94.
122. Datta DV, Khurro MS, Mattocks AR, Aikat BK, Chhuttani PN. Herbal medicines and veno-occlusive disease in India. Postgrad Med J 1978;54:511-5.
123. Lemberg A, Calabrese G, Majowicz M, Peredo H, Scorticati C, Filinger E, et al. Prostanoid production in endothelial and Kupffer liver cells from monocrotaline intoxicated rats. Hum Exper Toxicol 1998;17:564-9.
124. Boyer TD. Portal hypertension and bleeding esophageal varices. In: Zakim D, Boyer TD, editors. Hepatology: a textbook of liver disease. Philadelphia: W.B. Saunders Company;1990. p. 572-615.
125. Yan CC, Huxtable RJ. Effects of monocrotaline, a pyrrolizidine alkaloid, on glutathione metabolism in the rat. Biochem Pharmacol 1996;51:375-9.
126. DeLeve LD, Wang X, Kuhlenkamp JF, Kaplowitz N. Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: the role of glutathione and relevance to hepatic venoocclusive disease. Hepatology 1996;23:589-99.
127. 14C]monocrotaline in the rat. Drug Metab Dispos 1995;23:422-9.
128. Soto-Blanco B, Medeiros RMT, Guerra JL, Gorniak SL. Lack of protective action of cysteine against the fetotoxic effect of monocrotaline. Food Chem Toxicol 2001;39:635-9.
129. LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber H-P, et al. Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 2003;299:890-3.
130. Gordon CJ, Coleman WB, Grisham JW. Bax-mediated apoptosis in the livers of rats after partial hepatectomy in the retrorsine model of hepatocellular injury. Hepatology 2000;32:312-20.
131. Dabeva MD, Laconi E, Oren R, Petkov PM, Hurston E, Shafritz DA. Liver regeneration and alpha-fetoprotein messenger RNA expression in the retrorsine model for hepatocyte transplantation. Cancer Res 1998;58:5825-34.
132. Fausto N. Hepatic regeneration. In: Zakim D, Boyer T, editors. Hepatology: a textbook of liver diseases. Philadelphia: Saunders; 1990. p. 49-64.
133. Tilghman S, Belayew A. Transcriptional control of the murine albumin/α-fetoprotein locus during development. Proc Natl Acad Sci USA 1982;79:5254-7.
134. Leffert HL, Koch KS, Lu XP, Brenner DA, Karin M, Skelly HF, et al. Cellular and molecular biology of hepatocyte growth, regeneration and gene expression. In: Nishizuka Y, et al., editors. The biology and medicine of signal transduction, advances in second messenger and phosphoprotein research. New York: Raven Press; 1990. p. 352-8.
135. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, et al. Bcl-x,a Bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 1993;74:597-608.
136. Miyashita T, Reed J. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 1995;80:293-9.
137. Green D, Reed J. Mitochondria and apoptosis. Science 1998;281:1309-12.
138. Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature 2001;410:549-54.
139. Mitchell C, Mallet VO, Guidotti JE, Goulenok C, Kahn A, Gilgenkrantz H. Liver repopulation by Bcl-x(L) transgenic hepatocytes. Am J Pathol 2002;160:31-5.
140. Selzner M, Ru-diger HA, Selzner N, Thomas DW, Sindram D, Clavien PA. Transgenic mice overexpressing human Bcl-2 are resistant to hepatic ischemia and reperfusion. J Hepatol 2002;36:218-25.
141. Vogelstein B, Kinzler KW. Achilles' heel of cancer? Nature 2001; 412:865-6.
142. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery Jr CA, Butel JS, et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992;356:215-21.
143. Yap EP, Cooper K, Maharaj B, McGee JO. p53 codon 249ser hotspot mutation in HBV-negative hepatocellular carcinoma. Lancet 1993;341:251.
144. Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci USA 2001;98:14601-6.
145. Sun Z, Lu P, Gail MH, Pee D, Zhang Q, Ming L, et al. Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1. Hepatology 1999;30:379-83.
146. Wang H, Dick R, Yin H, Licad-Coles E, Kroetz DL, Szklarz G, et al. Structure-function relationships of human liver cytochromes P450 3A: aflatoxin B1 metabolism as a probe. Biochemistry 1998;37:12536-45.
147. Hirono I, Mori H, Haga M. Carcinogenic activity of Symphytum officinale. J Natl Cancer Inst 1978;61:865-9.
148. Kew MC. Hepatic tumors and cysts. In: Feldman M, Scharschmidt BF, Sleisenger MH, editors. Gastrointestinal and liver disease. Philadelphia: W.B. Saunders Company; 1998. p. 1364-87.
149. Buck M, Poli V, van der Geer P, Chojkier M, Hunter T. Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBPβ is required for hepatocyte proliferation induced by TGFα. Mol Cell 1999;4:1087-92.
150. Hunter T, Karin M. The regulation of transcription by phosphorylation. Cell 1992;70:375-87.
151. Hunter T, Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell 1994;79:573-82.
152. Svoboda DJ, Reddy JK. Malignant tumors in rats given lasiocarpine. Cancer Res 1972;32:908-12.
153. Rao MS, Reddy JK. Malignant neoplasms in rats fed lasiocarpine. Br J Cancer 1978;37:289-93.
154. Hirono I, Haga M, Fujii M, Matsuura S, Matsubara N, Nakayama M, et al. Induction of hepatic tumors in rats by senkirkine and symphytine. J Natl Cancer Inst 1979;63:469-72.
155. Kay JM, Harris P, Heath D. Pulmonary hypertension produced in rats by ingestion of Crotalaria spectabilis seeds. Thorax 1967;22:176-9.
156. Ohtsubo K, Ito Y, Saito M, Furuya T, Hikichi M. Hypertrophy of pulmonary arteries and arterioles with cor pulmonale in rats induced by seneciphylline, a pyrrolizidine alkaloid. Experientia 1977;33:498-9.
157. 3H-senecionine to DNA of rat liver, lung and kidney. Chem Biol Interact 1985;54:57-69.
158. Bruick RK, McKnight SL. Oxygen sensing gets a second wind. Science 2002;295:807-8.
159. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001;294:1337-40.
160. Peterkofsky B, Chojkier M, Bateman J. Determination of collagen synthesis in tissue and cell culture systems. In: Furthmayr H, editor. Immunochemistry of the extracellular matrix. Boca Raton, FL: CRC Press, Inc; 1982. p. 19-47.
161. Tanimoto K, Makino Y, Pereira T, Poellinger L. Mechanism of regulation of the hypoxia-inducible factor-1α by the von Hippel-Lindau tumor suppressor protein. EMBO J 2000;19:4298-309.
162. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 1998;95:7987-92.
163. Martin JL, Pumford NR, LaRosa AC, Martin BM, Gonzaga HMS, Beaven MA, et al. A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity. Biochem Biophys Res Commun 1991;178:679-85.
164. Houglum K, Ramm GA, Crawford DHG, Witztum JL, Powell LW, Chojkier M. Excess iron induces hepatic oxidative stress and transforming growth factor β1 in genetic hemochromatosis. Hepatology 1997;26:605-10.
165. Wagner JG, Petry TW, Roth RA. Characterization of monocrotaline pyrrole-induced DNA cross-linking in pulmonary artery endothelium. Am J Physiol 1993;264:L517-22.
166. Thomas HC, Lamé MW, Morin D, Wilson DW, Segall HJ. Prolonged cell-cycle arrest associated with altered cdc2 kinase in monocrotaline pyrrole-treated pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1998;19:129-42.
167. Hosoda Y. Pathology of pulmonary hypertension: a human and experimental study. Pathol Int 1994;44:241-67.
168. Lipke DW, Aziz SM, Fagerland JA, Majesky MW, Arcot SS. Tenascin synthesis, deposition, and isoforms in monocrotaline-induced pulmonary hypertensive rat lungs. Am J Physiol 1996;271(Lung Cell. Mol. Physiol. 15):L208-15.
169. Lipke DW, Arcot SS, Gillespie MN, Olson JW. Temporal alterations in specific basement membrane components in lungs from monocrotaline-treated rats. Am J Respir Cell Mol Biol 1993;9:418-28.
170. Frasch HF, Marshall C, Marshall BE. Endothelin-1 is elevated in monocrotaline pulmonary hypertension. Am J Physiol 1999;276:L304-10.
171. A receptor blockade improves nitric oxide-mediated vasodilation in monocrotaline-induced pulmonary hypertension. Circulation 1998;97:2169-74.
172. Mathew R, Zeballos GA, Tun H, Gewitz MH. Role of nitric oxide and endothelin-1 in monocrotaline-induced pulmonary hypertension in rats. Cardiovasc Res 1995;30:739-46.
173. Tyler RC, Muramatsu M, Abman SH, Stelzner TJ, Rodman DM, Bloch KD, et al. Variable expression of endothelial NO synthase in three forms of rat pulmonary hypertension. Am J Physiol 1999;276:L297-L303.
174. Stamler JS. Redox signaling: nitrosylation and related interactions of nitric oxide. Cell 1994:78:931-6.
175. Irukayama-Tomobe Y, Sakai S, Miyauchi T. Chronic treatment with probucol effectively inhibits progression of pulmonary hypertension in rats. Life Sci 2000;67:2017-23.
176. Nagaya N, Yokoyama C, Kyotani S, Shimonishi M, Morishita R, Uematsu M, et al. Gene transfer of human prostacyclin synthase ameliorates monocrotaline-induced pulmonary hypertension in rats. Circulation 2000;102:2005-10.
177. Zhu L, Wigle D, Hinek A, Kobayashi J, Ye C, Zuker M, et al. The endogenous vascular elastase that governs development and progression of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme related to the serine proteinase adipsin. J Clin Invest 1994;94:1163-71.
178. Partovian C, Adnot S, Eddahibi S, Teiger E, Levame M, Dreyfus P, et al. Heart and lung VEGF mRNA expression in rats with monocrotaline- or hypoxia-induced pulmonary hypertension. Am J Physiol 1998;275(Heart Circ. Physiol. 44):H1948-56.
179. Arcot SS, Lipke DW, Gillespie MN, Olson JW. Alterations of growth factor transcripts in rat lungs during development of monocrotaline-induced pulmonary hypertension. Biochem Pharmacol 1993;46:1086-91.
180. Ronis MJ, Ingelman-Sundberg M, Badger TM. Induction, suppression and inhibition of multiple hepatic cytochrome P450 isozymes in the male rat and bobwhite quail (Colinus virginianus) by ergosterol biosynthesis inhibiting fungicides (EBIFs). Biochem Pharmacol 1994;48:1953-65.
181. Cotreau MM, von Moltke LL, Harmatz JS, Greenblatt DJ. Molecular and pharmacokinetic evaluation of rat hepatic and gastrointestinal cytochrome P450 induction by tamoxifen. Pharmacology 2001;63:210-9.