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Protective effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on endotoxin-induced acute lung injury in rats

Objective

To determine whether rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, decreases the severity of endotoxin-induced acute lung injury and to investigate cellular mechanisms contributing to these effects.

Setting

A university research laboratory.

Interventions

Male Wistar rats were allocated into six groups (n = 6 for each group): (a) Sham-vehicle group: rats were treated with 10% dimethyl sulphoxide (DMSO) (vehicle for rosiglitazone) 30 min prior to saline; (b) Sham-rosiglitazone group: same as the Sham-vehicle group except that rosiglitazone (0.3 mg/kg, intravenously [i.v.]) was administered instead of DMSO; (c) Sham-GW9662 group: identical to Sham-vehicle group except that GW9662 (0.3 mg/kg, i.v.) was administered instead of DMSO; (d) LPS-vehicle group: rats were treated with DMSO 30 min before they were challenged with lipopolysaccharide (LPS) (6 mg/kg, i.v.); (e) Rosiglitazone-LPS group: rats were treated with rosiglitazone 30 min before they were subjected to LPS; (f) GW9662-rosiglitazone group: identical to Rosiglitazone-LPS group, but GW9662 was administered 20 min before rosiglitazone. Rats were killed at 4 hours after the injection of LPS and the lungs were collected.

Measurements and results

Pretreatment with rosiglitazone markedly attenuated the degree of (a) tissue injury and pulmonary edema, (b) neutrophils infiltration and lipid peroxidation, (c) expression of inducible nitric oxide synthase and production of nitric oxide, (d) formation of nitrotyrosine in the lungs of LPS-treated rats. The specific PPAR-γ antagonist GW9662 significantly antagonized the effects of rosiglitazone.

Conclusions

These findings support the view that rosiglitazone and other potent PPAR-γ agonists may be useful in the therapy of endotoxin-induced acute lung injury.

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Liu, D., Zeng, B., Zhang, S. et al. Protective effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on endotoxin-induced acute lung injury in rats. Crit Care 9, P201 (2005). https://doi.org/10.1186/cc3264

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Keywords

  • Nitric Oxide
  • Pulmonary Edema
  • Rosiglitazone
  • Neutrophil Infiltration
  • Nitrotyrosine