| First Author | Pozdeev VI | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 7938 |
| PubMed ID | 28801579 | Mgi Jnum | J:323704 |
| Mgi Id | MGI:6869622 | Doi | 10.1038/s41598-017-07640-8 |
| Citation | Pozdeev VI, et al. (2017) TNFalpha induced up-regulation of Na(+),K(+),2Cl(-) cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity. Sci Rep 7(1):7938 |
| abstractText | The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH4(+). Cellular NH4(+) uptake is accomplished mainly by the Na(+),K(+),2Cl(-) cotransporter. Here we show that hepatic clearance of NH4(+) is impaired in TNFalpha deficient as well as TNFR1&TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH4(+), TNFalpha deficient mice and TNFR1 deficient mice were protected against acute ammonia intoxication. While 54% of the wild-type mice and 60% of TNFR2 deficient mice survived an NH4(+) load, virtually all TNFalpha deficient mice and TNFR1 deficient mice survived the treatment. Conversely, TNFalpha treatment of wild type mice sensitized the animals to the toxic effects of an NH4(+) load. The protection of TNFalpha-deficient mice against an NH4(+) load was paralleled by decreased cerebral expression of NKCC1. According to the present observations, inhibition of TNFalpha formation and/or NKCC1 may be strategies to favorably influence the clinical course of hepatic encephalopathy. |
