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SPHINGANINE-1-PHOSPHATE ATTENUATES BOTH HEPATIC AND RENAL INJURY INDUCED BY HEPATIC ISCHEMIA AND REPERFUSION IN MICE
| Content Provider | Scilit |
|---|---|
| Author | D'Agati, Vivette D. Park, Sang Won Kim, Mihwa Chen, Sean W. C. Lee, H. Thomas |
| Copyright Year | 2010 |
| Description | Journal: Shock Hepatic ischemia/reperfusion (I/R) injury is a major complication after liver transplantation, major hepatic resection, or prolonged portal vein occlusion. Furthermore, acute kidney injury is frequent after hepatic I/R and greatly increases postoperative complications. Sphinganine-1-phosphate is a sphingolipid with uncharacterized physiological effects. We serendipitously determined that plasma levels of sphinganine-1-phosphate fell significantly after liver I/R in mice. In this study, we hypothesized that repletion of plasma sphinganine-1-phosphate would protect against liver and kidney injuries after liver I/R. C57BL/6 mice were subjected to 60 min of partial hepatic I/R and treated with either vehicle or with sphinganine-1-phosphate (given immediately before and 2 h after reperfusion). Vehicle-treated mice subjected to liver I/R developed acute liver and kidney injuries with elevated plasma alanine aminotransferase and creatinine 5 and 24 h after liver I/R. However, liver and kidney injuries were significantly attenuated with sphinganine-1-phosphate treatment. Sphinganine-1-phosphate markedly inhibited liver and kidney necrosis and apoptosis 24 h after liver I/R. Moreover, sphinganine-1-phosphate attenuated neutrophil infiltration, reduced plasma IL-6 and TNF-α upregulation, and preserved liver and kidney vascular integrity while reducing liver and kidney F-actin degradation after liver I/R. Finally, sphinganine-1-phosphate-mediated hepatic and renal protection was blocked by VPC23019, an antagonist for sphingosine-1-phosphate type 1 receptor. Therefore, sphinganine-1-phosphate improves acute liver and kidney injuries after hepatic I/R via sphingosine-1-phosphate type 1 receptor-mediated inhibition of necrosis and apoptosis and by improving vascular integrity. Harnessing the mechanisms of cytoprotection with sphinganine-1-phosphate activation may lead to new therapies for perioperative hepatic I/R injury and subsequent remote organ injury. |
| Related Links | http://europepmc.org/articles/pmc2794916?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794916/pdf |
| Ending Page | 42 |
| Page Count | 12 |
| Starting Page | 31 |
| ISSN | 15400514 |
| DOI | 10.1097/shk.0b013e3181c02c1f |
| Journal | Shock |
| Issue Number | 1 |
| Volume Number | 33 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2010-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Shock Peripheral Vascular Disease Apoptosis, Dihydrosphingosine-1-phosphate, Inflammation, Kidney, Liver, Necrosis, Sphingolipid, Sphingosine-1-phosphate |
| Content Type | Text |
| Resource Type | Article |
| Subject | Emergency Medicine Critical Care and Intensive Care Medicine |
