| First Author | Zhu JH | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 404 |
| Issue | 1 | Pages | 559-63 |
| PubMed ID | 21145306 | Mgi Jnum | J:167441 |
| Mgi Id | MGI:4868295 | Doi | 10.1016/j.bbrc.2010.12.025 |
| Citation | Zhu JH, et al. (2011) Lipopolysaccharide-induced hepatic oxidative injury is not potentiated by knockout of GPX1 and SOD1 in mice. Biochem Biophys Res Commun 404(1):559-63 |
| abstractText | Knockout of copper, zinc-superoxide dismutase (SOD1) and (or) cellular glutathione peroxidase (GPX1) has been reported to have dual impacts on coping with free radical-induced oxidative injury. Because bacterial endotoxin lipopolysaccharide (LPS) triggers inflammatory responses involving the release of cytokines, nitric oxide and superoxide in targeted organs such as liver, in this study we used SOD1 knockout (SOD1-/-), GPX1 knockout (GPX1-/-), GPX1 and SOD1 double-knockout (DKO) and their wild-type (WT) mice to investigate the role of these two antioxidant enzymes in LPS-induced oxidative injury in liver. Mice of the four genotypes (2month old) were killed at 0, 3, 6 or 12h after an i.p. injection of saline or 5mg LPS/kg body weight. The LPS injection caused similar increase in plasma alanine aminotransferase among the four genotypes. Hepatic total glutathione (GSH) was decreased (P<0.05) compared with the initial values by the LPS injection at all time points in the WT mice, but only at 6 and 12h in the other three genotypes. The GSH level in the DKO mice was higher (P<0.05) than in the WT at 6h. Although the LPS injection resulted in substantial increases in plasma NO in a time-dependent manner in all genotypes, the NO level in the DKO mice was lower (P<0.05) at 3, 6 and 12h than in the WT. The level in the GPX1-/- and SOD1-/- mice was also lower (P<0.05) than in the WT at 3h. The LPS-mediated hepatic protein nitration was detected in the WT and GPX1-/- mice at 3, 6 or 12h, but not in the SOD1-/-. In conclusion, knockout of SOD1 and (or) GPX1 did not potentiate the LPS-induced liver injury, but delayed the induced hepatic GSH depletion and plasma NO production. |
