Inflammatory Response Modulation through a PPARγ Agonist during Surgically Induced Visceral Ischemia in an Animal Model.

BACKGROUND: Ischemia/reperfusion (I/R) injury represents one of the most severe complications in vascular surgery where cross-clamping of the aorta and subsequent visceral ischemia are a recurrent issue. The literature describes a family of nuclear receptors, that is, peroxisome proliferator-activated receptors (PPARs), in particular PPARγ isoform, which are important modulators of vascular inflammation resulting from I/R injury. The aim of our study is to evaluate how PPARγ agonist administration could reduce local and systemic inflammatory response after I/R injury during aortic supraceliac clamping in animal model.

METHODS: Our model includes 16 rats divided as follows: 8 rats in the placebo control group (PlacG) were operated on without having been administered of any drugs during the preoperative period, whereas the 8 rats in the pioglitazone group (PioG) were pretreated with pioglitazone. Renal and visceral ischemias were induced in the rats by supraceliac aortic clamping. Rats were sacrificed after surgery, and then, we collected blood samples to measure serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and one of the kidneys and a segment of the liver to perform histological analysis.

RESULTS: Considering both cytokines in the PioG, there has been a negative trend in serum concentrations, whereas in the PlacG, we observed an increasing trend. The high standard deviation observed in our study is mainly due to the small population of the cohort. Histologic examination of the kidney showed more severe damage in the placebo group as compared to the PioG with more evident differences in tubular and tubulointerstitial scores.

CONCLUSIONS: Our observations show that administering pioglitazone can partially reduce secondary inflammatory response in the ischemic insult especially in endothelial and perivascular tissues.