Effects of rosiglitazone, an agonist of the peroxisome proliferator-activated receptor γ, on intestinal damage induced by Escherichia coli lipopolysaccharide in weaned pigs

Objective-To determine whether rosiglitazone, an agonist of the peroxisome proliferator-activated receptor (PPAR) gamma, could alleviate intestinal damage induced by Escherichia coli lipopolysaccharide (LPS) in weaned pigs. Animals-18 weaned pigs (mean +/- SD age, 28 +/- 3 days). Procedures-Pigs were allocated to 3 treatments (6 pigs/treatment). Control pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with sterile saline (0.9% NaCl) solution, LPS-treated pigs were injected IP with dimethyl sulfoxide and then injected 30 minutes later with LPS (100 mu g/kg, IF), and rosiglitazone plus LPS-treated pigs were injected with rosiglitazone (3 mg/kg, IF) and then injected 30 minutes later with LPS (100 mu g/kg, IF). Pigs were euthanized 3 hours after challenge exposure, and samples of the small intestines were collected for histologic, biochemical, and immunohistochemical examination. Results-Rosiglitazone alleviated LPS-induced intestinal damage, which was manifested as a lower crypt depth in the duodenum and a higher villus height-to-crypt depth ratio in the duodenum, jejunum, and ileum. Rosiglitazone also mitigated inhibition of crypt cell proliferation in the jejunum and ileum induced by LPS injection. Pretreatment with rosiglitazone significantly increased the number of cells that stained for PPAR gamma and significantly decreased the number of cells that stained for inducible nitric oxide synthase. Conclusions and Clinical Relevance-Rosiglitazone alleviated intestinal damage induced by LPS injection in weaned pigs. The protective effects of rosiglitazone on the intestines may be associated with inhibition of intestinal proinflammatory mediators, such as inducible nitric oxide synthase. (Am J Vet Res 2010;71:1331-1338)