Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model

Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, in gut barrier failure during experimental peritonitis in rats.

Male rats were randomly divided into three groups as follows: sham, sepsis, and sepsis + pioglitazone. Sepsis was achieved by means of the cecal ligation and puncture (CLP). Pioglitazone was administered intraperitoneally (10 mg/kg/d) for 7 d before the experiment. Animals were killed at 24 h or followed 72 h for survival. The tissue level of tumor necrosis factor-α, interleukin-6, superoxide dismutase, malondialdehyde, and myeloperoxidase was measured. Intestinal mucosa injury was assessed histologically. The plasma fluorescein isothiocyanate-dextran, D-lactic acid, and intestinal diamine oxidase were determined to evaluate the permeability and integrity of intestinal mucosal epithelium. Vena cava blood and tissue samples were used to monitor bacterial translocation.

Intestinal inflammation, oxidize stress, neutrophil infiltration, morphology injury, and impaired permeability of the small intestine in the CLP group were found more severe than those in the sham group. Application of pioglitazone not only minimized all the indicators of intestinal injury and barrier failure but also improved the survival of septic rats induced by CLP.

Our novel findings suggest that pioglitazone could protect against intestinal injury and maintain intestinal barrier integrity and might be a useful strategy to ameliorate intestinal failure in polymicrobial sepsis.