High risk of
cardiovascular diseases caused by existing
PPAR-γ agonists such as
rosiglitazone and
pioglitazone has been recently reported.
CKD-501 is a novel selective
PPAR-γ agonist as a potential target to reduce cardiovascular risk in
non-insulin dependent diabetes mellitus (
NIDDM). In this study, We investigated potential
cardiotoxicity of
CKD-501 and compared its toxicity with that of
rosiglitazone or
pioglitazone using db/db mice. After 12-week repeated administration of
CKD-501 at doses of 3, 10 and 30 mg/kg/day or
rosiglitazone at doses of 10 and 30 mg/kg/day or
pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And
lipid accumulation and apoptosis in heart muscle were examined by
oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of
pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as
pioglitazone >
CKD-501 ≥
rosiglitazone. However,
lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell
hypertrophy of
CKD-501 are relatively lower than that of
pioglitazone and similar to
rosiglitazone. And it is suggested that the myocardial cell
hypertrophy of
CKD-501 are less adverse in clinical use for the management of the
NIDDM.