Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors alpha and gamma agonist, following oral administration to Sprague Dawley rats for 94-101 weeks
- Authors
- Lee, Hee Su; Chang, Minsun; Lee, Ji-Eun; Kim, Woojin; Hwang, In-Chang; Kim, Dal-Hyun; Park, Hyun-Kyu; Choi, Hyun-Ji; Jo, Woori; Cha, Shin-Woo; Son, Woo-Chan
- Issue Date
- Jul-2014
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- CKD-501; Carcinogenicity; Dual PPAR alpha/gamma agonist
- Citation
- REGULATORY TOXICOLOGY AND PHARMACOLOGY, v.69, no.2, pp 207 - 216
- Pages
- 10
- Journal Title
- REGULATORY TOXICOLOGY AND PHARMACOLOGY
- Volume
- 69
- Number
- 2
- Start Page
- 207
- End Page
- 216
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10867
- DOI
- 10.1016/j.yrtph.2014.04.003
- ISSN
- 0273-2300
1096-0295
- Abstract
- CKD-501 is a peroxisome proliferator-activated receptor (PPAR) agonist. The current study was conducted in Sprague Dawley (SD) rats for 94-101 weeks to investigate the carcinogenic potential of CKD-501. 60 males received 0, 0.03, 0.12, or 1.0 mg/kg/day, which was changed after 66 weeks to 0.24 mg/kg/day due to increased mortality, while 60 females received 0, 0.03, 0.06, or 0.12 mg/kg/day throughout the study period. After switching the dosage, no significant changes in the survival rates were observed. Non-neoplastic lesions such as bladder transitional cell hyperplasia and a diminished corpus luteum were observed in females administered 0.12 mg/kg/day and the right chamber dilation and left ventricular hypertrophy were increased dose dependently in both males and females. Non-neoplastic lesions such as bone marrow hypoplasia and fat cell proliferation and neoplastic lesions such as lipomas and liposarcomas observed in males and/or females were considered expected pharmacological effects for this compound. Compared to rosiglitazone, CKD-501 had a 4.4-fold higher margin of safety for tumor induction and did not cause bladder carcinoma as was observed with pioglitazone. (C) 2014 Elsevier Inc. All rights reserved.
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