Effect of gender, dose, and time on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione (DCPT)-induced hepatotoxicity in Fischer 344 rats.
1. The thiazolidinedione ring present in drugs available for type II diabetes can contribute to hepatic injury. Another thiazolidinedione ring-containing compound, 3-(3,5-dichlorophenyl)-2,4-thiazoli-dinedione (DCPT), produces liver damage in rats. Accordingly, the effects of gender, dose, and time on DCPT hepatotoxicity were therefore evaluated. 2. Male rats were more sensitive to DCPT (0.4-1.0 mmol kg(-1) by intraperitoneal administration) as shown by increased serum alanine aminotransferase levels and altered hepatic morphology 24 h post-dosing. Effects in both genders were dose dependent. In males, DCPT (0.6 mmol kg(-1)) produced elevations in alanine aminotransferases and changes in liver sections 3 h after dosing that progressively worsened up to 12 h. DCPT-induced renal effects were mild. 3. It is concluded that male rats are more susceptible to DCPT hepatotoxicity and that damage occurs rapidly. DCPT primarily affects the liver and can be a useful compound to investigate the role of the thiazolidinedione ring in hepatic injury. However, the gender dependency and rapid onset of DCPT hepatotoxicity require further investigation.
Patel
N N
NN
Department of Pharmaceutical Sciences, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA.
Crincoli
C M
CM
Kennedy
E L
EL
Frederick
D M
DM
Tchao
R
R
Harvison
P J
PJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione