Hepatic and intestinal changes in rats treated with T-0126, a microsomal triglyceride transfer protein (MTP) inhibitor

Journal of Toxicological Sciences

Volumn 32, Issue 2, 2007, Pages 161-177

  Miyazaki, Toshiko ^a   Miwa, Satoko ^a   Kodama, Hirohiko ^a   Yamada, Harutami ^a   Nagata, Koichi ^a   Toriumi, Wataru ^a   Kitamura, Kazuyuki ^a   Nakayama, Hiroyuki ^b   Kume, Eisuke ^a  

^a MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

Fat accumulation; Intestine; Liver; Microsomal triglyceride transfer protein inhibitor; Rat

Indexed keywords

ANTIOXIDANT; FAT; LIPID; MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN INHIBITOR; T 0126; UNCLASSIFIED DRUG; VITAMIN K GROUP;

AMINOTRANSFERASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; GASTROINTESTINAL TOXICITY; INFLAMMATION; LIPID BLOOD LEVEL; LIPID STORAGE; LIVER TOXICITY; MALABSORPTION; MALE; NONHUMAN; RAT; RAT STRAIN;

RATTUS;

EID: 34249825176     PISSN: 03881350     EISSN: 18803989     Source Type: Journal    
DOI: 10.2131/jts.32.161     Document Type: Article

References (17)

1. Chang, G., Ruggeri, R.B. and Harwood, H.J.Jr. (2002): Microsomal triglyceride transfer protein (MTP) inhibitors: Discovery of clinically active inhibitors using high-throughput screening and parallel synthesis paradigms. Current Opinion in Drug Discovery & Development., 5, 562-570.
2. Dunnett, C.W. (1955): A multiple comparison procedure for comparing several treatments with a control. Journal of the American Statistical Association., 50, 1096-1121.
3. Folch, J., Lees, M. and Sloane Stanley, G.H. (1957): A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem., 226, 497-509.
4. Jamil, H., Dickson, J.K. Jr., Chu, C.H., Lago, M.W., Rinehart, J.K., Biller, S.A., Gregg, R.E. and Wetterau, J.R. (1995): Microsomal triglyceride transfer protein. Specificity of lipid binding and transport. J. Biol. Chem., 270, 6549-6554.
5. Katoh, N., Minoura, S., Uchida, E. and Takahashi, K. (1993): Effect of estradiol administration and subsequent nonfeeding on liver estrogen receptor, serum apolipoprotein B-100, and serum triglycerides concentrations in steers. Am. J. Vet. Res., 54, 1476-1482.
6. Kawanishi, H., Kamaya, H., Ando, A., Kusama, M., Annaka, M., Harada, N., Tsujishima, H., Yasuda, K., Nagata, K., Hirano, N., Kume, E., Kodama, H. and Yamada, H. (2005): Discovery of Novel Potent MTP Inhibitors. 24th Symposium on Medicinal Chemistry, Osaka, Japan, poster 2P-16 (in Japanese).
7. Negishi, I. and Aizawa, Y. (1975): Sex difference in the development of fatty liver by orotic acid. Jpn. J. Pharmacol., 25, 289-294.
8. Ohashi, K. (1998): The Lipid., 9, 502-508(in Japanese).
9. Raabe, M., Flynn, L.M., Zlot, C.H., Wong, J.S., Véniant, M.M., Hamilton, R.L. and Young, S.G. (1998): Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes. Proc. Natl. Acad. Sci. USA., 95, 8686-8691.
10. Raabe, M., Véniant, M.M., Sullivan, M.A., Zlot, C.H., Björkegren, J., Nielsen, L.B., Wong, J.S., Hamilton, R.L. and Young, S.G. (1999): Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J. Clin. Invest., 103, 1287-1298.
11. Righetti, A.B. and Kaplan, M.M. (1971): The origin of the serum alkaline phosphatase in normal rats. Biochim. Biophys. Acta., 230, 504-509.
12. Robl, J.A., Sulsky, R., Sun, C.Q., Simpkins, L.M., Wang, T., Dickson, J.K. Jr., Chen, Y., Magnin, D.R., Taunk, P., Slusarchyk, W.A., Biller, S.A., Lan, S.J., Connolly, F., Kunselman, L.K., Sabrah, T., Jamil, H., Gordon, D., Harrity, T.W. and Wetterau, J.R. (2001): A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. J. Med. Chem., 44, 851-856.
13. Sorbera, L.A., Martín, L., Silvestre, J. and Castañer, J. (2000): Implitapide. Drugs of the Future., 25, 1138-1144.
14. Suarez, L., Valbuena, M.L., Moreno, A., Santonja, C., Gonzalez-Palacios, F., Camarero, C. and Escobar, H. (1987): Abetalipoproteinemia associated with hepatic and atypical neurological disorders. J. Pediatr. Gastroenterol. Nutr., 6, 799-802.
15. Wetterau, J.R., Aggerbeck, L.P., Bouma, M.E., Eisenberg, C., Munck, A. , Hermier, M. , Schmitz, J., Gay, G., Rader, D.J. and Gregg, R.E. (1992): Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science., 258, 999-1001.
16. Wetterau, J.R., Gregg, R.E., Harrity, T.W., Arbeeny, C., Cap, M., Connolly, F., Chu, C.H., George, R.J., Gordon, D.A., Jami l, H. , Jol ibois, K.G., Kunselman, L.K., Lan, S.J., Maccagnan, T.J., Ricci, B., Yan, M. , Young, D. , Chen, Y., Fryszman, O.M., Logan, J.V., Musial, C.L., Poss, M.A., Robl , J.A., Simpkins, L.M., Slusarchyk, W.A., Sulsky, R., Taunk, P., Magnin, D.R., Tino, J.A., Lawrence, R.M., Dickson, J.K. Jr. and Biller, S.A. (1998): An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits. Science., 282, 751-754.
17. Yin, M., Ikejima, K., Wheeler, M.D., Bradford, B.U., Seabra, V. , Forman, D.T., Sa to, N. and Thurman, R.G. (2000): Estrogen is involved in early alcohol-induced liver injury in a rat enteral feeding model. Hepatology., 31, 117-123.