HEPATIC AND INTESTINAL CHANGES IN RATS TREATED WITH T-0126, A MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN (MTP) INHIBITOR

• Published in: Journal of toxicological sciences Vol. 32; no. 2; pp. 161 - 177
• Main Authors: MIYAZAKI, MIWA, Satoko, KODAMA, Hirohiko, YAMADA, Harutami, NAGATA, Koichi, TORIUMI, Wataru, KITAMURA, Kazuyuki, KUME, Eisuke
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society of Toxicology 2007; Japan Science and Technology Agency
• Subjects: Administration, Oral; Animals; Benzamides - toxicity; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - metabolism; Chemistry, Clinical; Dose-Response Relationship, Drug; Female; Hematologic Tests; Hepatocytes - drug effects; Hepatocytes - ultrastructure; Indoles - toxicity; Intestine, Small - drug effects; Intestine, Small - metabolism; Intestine, Small - pathology; Lipids - blood; Liver - drug effects; Liver - metabolism; Liver - pathology; Lymph Nodes - drug effects; Lymph Nodes - metabolism; Lymph Nodes - pathology; Male; Microsomes - drug effects; Organ Size - drug effects; Rats; Rats, Inbred Strains
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.32.161

In the present study, we investigated the potential toxic effects of 2-week oral treatment with T-0126, a novel microsomal triglyceride transfer protein (MTP) inhibitor, on the liver and intestine in male and female rats. Administration of T-0126 decreased serum lipids and resulted in fat accumulation in the liver and the small intestine. In addition, slight changes in the liver, including an increase in serum aminotransferase (AST and ALT) activity, presence of focal inflammatory lesions, and prolongation of PT and APTT were observed after treatment with T-0126. These changes may be related to a mechanism based on malabsorption of fat, fat-soluble antioxidants, and vitamin K, although we cannot exclude other potential mechanisms such as direct cytotoxicity of T-0126.