Role of PPAR gamma in Acute Renal Failure

Objective: Acute Renal failure (ARF) is a common sequel to chronic diseases such as hypertension and Diabetes Mellitus. Understanding the mechanism involved in damaging the glomerular membrane at the molecular level is of significant importance since this will allow us to prevent molecular changes before they attain a level of irreversibility.Oxidative stress and nitric oxide (NO) play a significant role in the maintenance of renal tubular and glomerular function in health and illness. Enzymes responsible for either ROS generation or NO production are controlled by transcription factors such as peroxisome proliferator activated receptor gamma (PPARγ). Here, we hypothesized that oxidative stress during chronic disease process reduced PPARγ gene expression and therefore, NAD(P)H oxidase NO production. Design and method: We used a glycerol model of ARF in male Sprague-Dawly rats, divided in control and treated groups. ARF was induced using the standard method involving administration of 50% glycerol (v/v, 8 mL/kg, i.m). After 21 days of study period, the required amount of glycerol was administered as a deep intramuscular injection equally distributed to both hind legs. Rats were deprived of food and water for 24 hours after glycerol administration. After injecting glycerol, rats were placed in metabolic cages, and 24 hr urine was collected. Blood was collected via cardiac puncture under pentobarbital anesthesia (Na pentobarbital 50 mg/kg; i.p). Kidneys were processed for isolation of renal microvessels and subsequent biochemical and molecular biology analysis. Results: Our results indicated reduced PPARγ mRNA and protein expression and activity in ARF. Addition of PPARg inducer, Ciglitazone, increased PPARγ mRNA and protein expression and activity in ARF. Ciglitazone improved renal vascular reactivity that was exaggerated in ARF. We observed ~100% increase in 8-isoprostane level in the plasma of ARF rats compared control. Ciglitazone abolished the increase in free-radical generation significantly. Conclusion: Based on our data we are concluding that reduced PPARg has a definitive role in the kidney function. This work was supported by an Innovation grant from Texas Southern University. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.