Abstract
Troglitazone is an oral antidiabetic drug that is a ligand for peroxisome proliferator activated receptor γ (PPARγ). Based on other studies that have implicated an immunosuppressive role for PPARγ during inflammatory responses, we hypothesized that troglitazone treatment would improve survival in a murine model of endotoxemia and that the protective effect would be mediated by decreased expression of inflammatory mediators. C57Bl/6N x Sv/129 (wild-type [WT]) or PPARα null mice treated for 2 weeks with dietary troglitazone (0.1%) had significantly fewer deaths and a higher LD50value compared to control-fed mice when challenged with lipopolysaccharide (LPS). PPARα null mice were more sensitive to the lethal effects of LPS as evidenced by a 2-fold lower LD50(6.6 mg/kg) compared to WT mice (14.6 mg/kg). Troglitazone treatment had no significant effect on LPS-induced plasma TNF, glucose, or nitric oxide levels in WT or PPARα null mice at any of the time points examined. However, troglitazone treatment significantly reduced LPS-induced plasma IL-6 levels in both WT and PPARα null mice. The results of these studies suggest that troglitazone treatment protects mice against a lethal challenge of LPS, but whether or not this effect is mediated through decreased expression of inflammatory mediators remains unclear.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.