N-vinylpyrrolidone dimer, a novel formulation excipient, causes hepatic and thyroid hypertrophy through the induction of hepatic microsomal enzymes in rats

Toxicology Letters

Volumn 208, Issue 1, 2012, Pages 82-91

  Yang, Yi ^a   Ciurlionis, Rita ^a   Kowalkowski, Kenneth ^a   Marsh, Kennan C ^a   Bracken, William M ^a   Blomme, Eric A G ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Enzyme induction; Liver hypertrophy; Thyroid gland hypertrophy; Thyroid hormone metabolism; Transcriptome

Indexed keywords

CYTOCHROME P450 2B1; CYTOCHROME P450 3A1; DRUG METABOLIZING ENZYME; GLUCURONOSYLTRANSFERASE; LIOTHYRONINE; LIVER ENZYME; PHENOBARBITAL; POVIDONE; THYROID HORMONE; THYROTROPIN; THYROXINE; TRANSCRIPTOME;

ANIMAL CELL; ARTICLE; BIOSYNTHESIS; CONTROLLED STUDY; DRUG FORMULATION; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INDUCTION; GOITER; LIOTHYRONINE BLOOD LEVEL; LIVER CELL; LIVER HYPERTROPHY; NONHUMAN; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION; SPRAGUE DAWLEY RAT; THYROTROPIN BLOOD LEVEL; THYROXINE BLOOD LEVEL; TRANSCRIPTOMICS;

ANIMALS; CHEMISTRY, PHARMACEUTICAL; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCIPIENTS; GENE EXPRESSION PROFILING; HEPATOCYTES; HEPATOMEGALY; HYPERTROPHY; LIVER; MALE; MICROSOMES, LIVER; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PYRROLIDINONES; RATS; RATS, SPRAGUE-DAWLEY; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTORS, CYTOPLASMIC AND NUCLEAR; THYROID DISEASES; THYROID GLAND; THYROID HORMONES; TRANSCRIPTOME;

RATTUS;

EID: 80755184770     PISSN: 03784274     EISSN: 18793169     Source Type: Journal    
DOI: 10.1016/j.toxlet.2011.10.012     Document Type: Article

References (45)

1. Bachhav Y.G., Date A.A., Patravale V.B. Exploring the potential of N-methyl pyrrolidone as a cosurfactant in the microemulsion systems. Int. J. Pharm. 2006, 326:186-189.
2. Blomme E.A., Yang Y., Waring J.F. Use of toxicogenomics to understand mechanisms of drug-induced hepatotoxicity during drug discovery and development. Toxicol. Lett. 2009, 186:22-31.
3. Breitenbach J. Naturwissenschaften 1955, 42:440-441.
4. Breitenbach, J., Heger, R., Simon, D., 2003. Test system for characterizing the compatibility of bioactive substances and polyvinylpyrrolidone. United States Patent 6,599,931 (29.07.03).
5. Capen C. Toxic response of the endocrine system. Casarett & Doull's Toxicology: The Basic Science of Poisons 2008, 807-879. McGraw-Hill. C.D. Klaassen (Ed.).
6. Capen C.C., Martin S.L. The effects of xenobiotics on the structure and function of thyroid follicular and C-cells. Toxicol. Pathol. 1989, 17:266-293.
7. Clemmesen J., Fuglsang-Frederiksen V., Plum C.M. Are anticonvulsants oncogenic?. Lancet 1974, 1:705-707.
8. Corda D., Kohn L.D. Thyrotropin upregulates alpha 1-adrenergic receptors in rat FRTL-5 thyroid cells. Proc. Natl. Acad. Sci. U.S.A. 1985, 82:8677-8680.
9. Curran P.G., DeGroot L.J. The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr. Rev. 1991, 12:135-150.
10. DeGroot L.J., Quintans J. The causes of autoimmune thyroid disease. Endocr. Rev. 1989, 10:537-562.
11. Dickins M. Induction of cytochromes P450. Curr. Top. Med. Chem. 2004, 4:1745-1766.
12. Ennulat D., Walker D., Clemo F., Magid-Slav M., Ledieu D., Graham M., Botts S., Boone L. Effects of hepatic drug-metabolizing enzyme induction on clinical pathology parameters in animals and man. Toxicol. Pathol. 2010, 38:810-828.
13. Galanti M.R., Sparen P., Karlsson A., Grimelius L., Ekbom A. Is residence in areas of endemic goiter a risk factor for thyroid cancer?. Int. J. Cancer. 1995, 61:615-621.
14. Glatt C.M., Ouyang M., Welsh W., Green J.W., Connor J.O., Frame S.R., Everds N.E., Poindexter G., Snajdr S., Delker D.A. Molecular characterization of thyroid toxicity: anchoring gene expression profiles to biochemical and pathologic end points. Environ. Health Perspect. 2005, 113:1354-1361.
15. Goodwin B., Moore L.B., Stoltz C.M., McKee D.D., Kliewer S.A. Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol. Pharmacol. 2001, 60:427-431.
16. 2002. Guiding principles in the use of animals in toxicology. Adopted by the Society of Toxicology in July 1989. Toxicol. Appl. Pharmacol. 178, 4.
17. Hewitt N.J., Lecluyse E.L., Ferguson S.S. Induction of hepatic cytochrome P450 enzymes: methods, mechanisms, recommendations, and in vitro-in vivo correlations. Xenobiotica 2007, 37:1196-1224.
18. Hill R.N., Crisp T.M., Hurley P.M., Rosenthal S.L., Singh D.V. Risk assessment of thyroid follicular cell tumors. Environ. Health Perspect. 1998, 106:447-457.
19. Hood A., Hashmi R., Klaassen C.D. Effects of microsomal enzyme inducers on thyroid-follicular cell proliferation, hyperplasia, and hypertrophy. Toxicol. Appl. Pharmacol. 1999, 160:163-170.
20. Hood A., Liu J., Klaassen C.D. Effects of phenobarbital, pregnenolone-16alpha-carbonitrile, and propylthiouracil on thyroid follicular cell proliferation. Toxicol. Sci. 1999, 50:45-53.
21. Hood A., Liu Y.P., Gattone V.H., Klaassen C.D. Sensitivity of thyroid gland growth to thyroid stimulating hormone (TSH) in rats treated with antithyroid drugs. Toxicol. Sci. 1999, 49:263-271.
22. Jain P., Yalkowsky S.H. Solubilization of poorly soluble compounds using 2-pyrrolidone. Int. J. Pharm. 2007, 342:1-5.
23. Jones H.B., Clarke N.A. Assessment of the influence of subacute phenobarbitone administration on multi-tissue cell proliferation in the rat using bromodeoxyuridine immunocytochemistry. Arch. Toxicol. 1993, 67:622-628.
24. Kawamoto T., Sueyoshi T., Zelko I., Moore R., Washburn K., Negishi M. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol. Cell. Biol. 1999, 19:6318-6322.
25. Maglich J.M., Stoltz C.M., Goodwin B., Hawkins-Brown D., Moore J.T., Kliewer S.A. Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol. Pharmacol. 2002, 62:638-646.
26. Maronpot R.R., Yoshizawa K., Nyska A., Harada T., Flake G., Mueller G., Singh B., Ward J.M. Hepatic enzyme induction: histopathology. Toxicol. Pathol. 2010, 38:776-795.
27. McClain R.M., Levin A.A., Posch R., Downing J.C. The effect of phenobarbital on the metabolism and excretion of thyroxine in rats. Toxicol. Appl. Pharmacol. 1989, 99:216-228.
28. Moore L.B., Parks D.J., Jones S.A., Bledsoe R.K., Consler T.G., Stimmel J.B., Goodwin B., Liddle C., Blanchard S.G., Willson T.M., Collins J.L., Kliewer S.A. Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. 2000, 275:15122-15127.
29. Nebert D.W., Roe A.L., Dieter M.Z., Solis W.A., Yang Y., Dalton T.P. Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochem. Pharmacol. 2000, 59:65-85.
30. Olsen J.H., Boice J.D., Jensen J.P., Fraumeni J.F. Cancer among epileptic patients exposed to anticonvulsant drugs. J. Natl. Cancer Inst. 1989, 81:803-808.
31. Polakis P. Wnt signaling and cancer. Genes Dev. 2000, 14:1837-1851.
32. Qatanani M., Zhang J., Moore D.D. Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology 2005, 146:995-1002.
33. Refetoff S., Weiss R.E., Usala S.J. The syndromes of resistance to thyroid hormone. Endocr. Rev. 1993, 14:348-399.
34. Ringel M.D., Hayre N., Saito J., Saunier B., Schuppert F., Burch H., Bernet V., Burman K.D., Kohn L.D., Saji M. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res. 2001, 61:6105-6111.
35. Saji M., Ringel M.D. The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. Mol. Cell Endocrinol. 2010, 321:20-28.
36. Semler D.E., Chengelis C.P., Radzialowski F.M. The effects of chronic ingestion of spironolactone on serum thyrotropin and thyroid hormones in the male rat. Toxicol. Appl. Pharmacol. 1989, 98:263-268.
37. Smith P., Williams E.D., Wynford-Thomas D. In vitro demonstration of a TSH-specific growth desensitising mechanism in rat thyroid epithelium. Mol. Cell Endocrinol. 1987, 51:51-58.
38. Smith P.F., Grossman S.J., Gerson R.J., Gordon L.R., Deluca J.G., Majka J.A., Wang R.W., Germershausen J.I., MacDonald J.S. Studies on the mechanism of simvastatin-induced thyroid hypertrophy and follicular cell adenoma in the rat. Toxicol. Pathol. 1991, 19:197-205.
39. Stringer B.M., Wynford-Thomas D., Williams E.D. In vitro evidence for an intracellular mechanism limiting the thyroid follicular cell growth response to thyrotropin. Endocrinology 1985, 116:611-615.
40. Waring J.F., Yang Y., Healan-Greenberg C.H., Adler A.L., Dickinson R., McNally T., Wang X., Weitzberg M., Xu X., Lisowski A., Warder S.E., Gu Y.G., Zinker B.A., Blomme E.A., Camp H.S. Gene expression analysis in rats treated with experimental acetyl-coenzyme A carboxylase inhibitors suggests interactions with the peroxisome proliferator-activated receptor alpha pathway. J. Pharmacol. Exp. Ther. 2008, 324:507-516.
41. Weng L., Dai H., Zhan Y., He Y., Stepaniants S.B., Bassett D.E. Rosetta error model for gene expression analysis. Bioinformatics 2006, 22:1111-1121.
42. Wu K.M., Farrelly J.G. Preclinical development of new drugs that enhance thyroid hormone metabolism and clearance: inadequacy of using rats as an animal model for predicting human risks in an IND and NDA. Am. J. Ther. 2006, 13:141-144.
43. Wynford-Thomas D., Stringer B.M., Williams E.D. Dissociation of growth and function in the rat thyroid during prolonged goitrogen administration. Acta Endocrinol. (Copenh) 1982, 101:210-216.
44. Younes M.N., Kim S., Yigitbasi O.G., Mandal M., Jasser S.A., Dakak Y.Y., Schiff B.A., El Naggar A., Bekele B.N., Mills G.B., Myers J.N. Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer. Mol. Cancer. Ther. 2005, 4:1146-1156.
45. Zabka T.S., Fielden M.R., Garrido R., Tao J., Fretland A.J., Albassam M.A., Singer T., Kolaja K.L. Characterization of xenobiotic-induced hepatocellular enzyme induction in rats: anticipated thyroid effects and unique pituitary gland findings. Toxicol. Pathol. 2011, 39:664-677.