Project description:Cardiac pathological hypertrophy is associated with a significantly increased risk of coronary heart disease and has been observed in diabetic patients treated with rosiglitazone, whereas most published studies do not suggest a similar increase in risk of cardiovascular events in pioglitazone-treated diabetic subjects. This study sought to understand the pathophysiological mechanisms underlying the disparate cardiovascular effects of rosiglitazone and pioglitazone and yield knowledge as to the causative nature of rosiglitazone-associated cardiac hypertrophy.
Project description: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.
