Effect of two 5-HT6 receptor antagonists on the rat liver: a molecular approach.
作者： L Suter , M Haiker , M C de Vera , S Albertini
关键词: Receptor 、 Toxicogenomics 、 Serotonin 、 Metabolic pathway 、 Pharmacology 、 Gene expression 、 Steatosis 、 5-HT6 receptor 、 Toxicity 、 Biology
摘要: Serotonin is involved in disorders of the central nervous system; thus, specific 5-HT6 receptor antagonists have therapeutic potential. Nevertheless, preclinical tests showed that Ro 65-7199 caused hepatic steatosis. Here, we investigated effects and 66-0074 using toxicogenomics. The profiles obtained after exposure rats to both compounds clearly show two pharmacologically closely related with different toxicological can be distinguished based on gene expression profiles. Moreover, side detected earlier toxicogenomics than conventional end points. A possible link between sterol metabolic pathway, induction CYP2B, fat accumulation was also established. Summarizing, allow according their toxicity provide mechanistic insights. results power as a tool for obtaining characteristic fingerprints at early time-points generating hypotheses.
nature.com
sci-hub.se 参考文章(34)
Taro E Akiyama, Jerrold M Ward, Frank J Gonzalez, Regulation of the Liver Fatty Acid-binding Protein Gene by Hepatocyte Nuclear Factor 1α (HNF1α) ALTERATIONS IN FATTY ACID HOMEOSTASIS INHNF1α-DEFICIENT MICE Journal of Biological Chemistry. ,vol. 275, pp. 27117- 27122 ,(2000) , 10.1074/JBC.M004388200
Y Suwa, Y Mizukami, K Sogawa, Y Fujii-Kuriyama, Gene structure of a major form of phenobarbital-inducible cytochrome P-450 in rat liver. Journal of Biological Chemistry. ,vol. 260, pp. 7980- 7984 ,(1985) , 10.1016/S0021-9258(17)39550-9
R. Mössner, A. Schmitt, Y. Syagailo, M. Gerlach, P. Riederer, K. P. Lesch, The serotonin transporter in Alzheimer's and Parkinson's disease. Journal of Neural Transmission-supplement. pp. 345- 350 ,(2000) , 10.1007/978-3-7091-6301-6_24
Françoise de Longueville, Dominic Surry, Georgina Meneses-Lorente, Vincent Bertholet, Valérie Talbot, Stephanie Evrard, Nathalie Chandelier, Andrew Pike, Phil Worboys, Jean-Paul Rasson, Béatrice Le Bourdellès, José Remacle, Gene expression profiling of drug metabolism and toxicology markers using a low-density DNA microarray Biochemical Pharmacology. ,vol. 64, pp. 137- 149 ,(2002) , 10.1016/S0006-2952(02)01055-9
W.D. Pennie, I. Kimber, Toxicogenomics; transcript profiling and potential application to chemical allergy. Toxicology in Vitro. ,vol. 16, pp. 319- 326 ,(2002) , 10.1016/S0887-2333(02)00007-3
David J. Waxman, Christopher Walsh, Cytochrome P-450 isozyme 1 from phenobarbital-induced rat liver: purification, characterization, and interactions with metyrapone and cytochrome b5. Biochemistry. ,vol. 22, pp. 4846- 4855 ,(1983) , 10.1021/BI00289A035
Kazuo Nakayama, Yorimasa Suwa, Yuzuru Mizukami, Kazuhiro Sogawa, Yoshiaki Fujii-Kuriyama, Cloning and sequencing of a novel rat cytochrome P450 2B-encoding gene Gene. ,vol. 136, pp. 333- 336 ,(1993) , 10.1016/0378-1119(93)90490-T
Michael Fountoulakis, Maria-Cristina de Vera, Flavio Crameri, Franziska Boess, Rodolfo Gasser, Silvio Albertini, Laura Suter, Modulation of gene and protein expression by carbon tetrachloride in the rat liver. Toxicology and Applied Pharmacology. ,vol. 183, pp. 71- 80 ,(2002) , 10.1006/TAAP.2002.9460
Isabelle Leclercq, Yves Horsmans, Jean-Pierre Desager, Nathalie Delzenne, André-Pierre Geubel, Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat content in animal models of steatosis in the absence of inflammation Journal of Hepatology. ,vol. 28, pp. 410- 416 ,(1998) , 10.1016/S0168-8278(98)80314-0
John Whysner, Peter M Ross, Gary M Williams, Phenobarbital mechanistic data and risk assessment: Enzyme induction, enhanced cell proliferation, and tumor promotion Pharmacology & Therapeutics. ,vol. 71, pp. 153- 191 ,(1996) , 10.1016/0163-7258(96)00067-8