Effect of rosiglitazone on cisplatin-induced nephrotoxicity.
OBJECTIVE
Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity.


METHODS
Eighteen male Sprague-Dawley rats weighing 150-200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis-Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically.


RESULTS
Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p<0.05) and group 2 (p<0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p>0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p<0.05). However, there were no significant differences between groups 1 and 2 (p>0.05).


CONCLUSIONS
This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.
Ozkaya
Ozan
O
Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
Yavuz
Oguzhan
O
Can
Bilge
B
Dilek
Melda
M
Savli
Evren
E
Acikgoz
Yonca
Y
Bedir
Abdülkerim
A
Akpolat
Tekin
T
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003404:Creatinine; D002945:Cisplatin