PPARγ Role on Ameliorating the Effects of Losartan in LPS-Induced Lung and Systemic Injuries in Mice

Background: The effects of losartan (Los) and GW9662 on lipopolysaccharides (LPS)-induced acute lung injury (ALI) and systemic inflammation were examined. Methods: Mice were administered saline or LPS (0.250 mg/kg) for seven days and were treated with Los (1 mg/kg), GW9662 (1 mg/kg), or their combination for ten days (n=7 per group). Total and differential white blood cells (WBC) in the blood and the bronchoalveolar lavage fluid (BALF), oxidant and anti-oxidant markers including malondialdehyde (MDA), total thiol, superoxide dismutase (SOD), and catalase (CAT) levels were measured in serum, the levels of interleukin-4 (IL-4), interferon gamma (IFN-γ), and transforming growth factor beta (TGF-β1) in the BALF, and lung histopathological changes were assessed. Results: In the LPS group, SOD, CAT, and thiol in serum, and TGF-β1 and IFN-γ levels and INF-γ/IL-4 ratio in the BALF were decreased, but WBC count in the blood and BALF, and serum MDA, BALF IL-4 level and lung pathological changes were significantly increased. Most variables were improved in the LPS group treated with Los or its combination with GW9662. Treatment with GW9662 alone did not change any variable. Conclusion: Although the preventive effect of Los may not be entirely mediated through the PPAR-γ receptor, the results indicate that the Los effect is partially reversed with GW9662 treatment, suggesting at least a partial involvement of the PPAR-γ pathway.