Trancriptional profiling of rat bladder after daily administration of Pioglitazone and Rosiglitazone in vivo (miRNA). Rattus norvegicus

The purpose of the study was to investigate the nongenotoxic carcinogenic effect of Pioglitazone. Pioglitazone is a PPARgamma agonist and is known to cause bladder tumours in male rats and an increase in the incidence of bladder cancer in humans has been observed in patients treated with Pioglitazone. Pioglitazone is not considered genotoxic or carcinogenic in mice and tumours are only observed in male rats suggesting a nongenotoxic mechanism of tumorigenesis. A suggested hypothesis is urinary calculi formation and subsequent irritation, hyperplasia and metaplasia. Rosiglitazone was used as reference compound as this PPARgamma agonist does not cause changes in the bladder but cause lipoma/liposarcoma in rats. Overall design: Sprague-Dawley rats were dosed for 3 time periods: 3, 28 or 90 days. The animals (10/sex/group) were dosed orally with vehicle (0.5 % methylcellulose), Pioglitazone (13 and 63 mg/kg/day) or Rosiglitazone (10 mg/kg/day). Bladder urothelium was isolated from 5 animals/sex/group and further processed for transcriptional profiling.