In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-08-11)
Abstract:
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 NH 4 + . Cellular NH 4 + uptake is accomplished mainly by the Na + ,K + ,2Cl − cotransporter. Here we show that hepatic clearance of NH 4 + is impaired in TNFα deficient as well as TNFR1 & TNFR2 double knockout mice, which both develop hyperammonemia. Despite impaired hepatic clearance of NH 4 + , TNFα 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 NH 4 + load, virtually all TNFα deficient mice and TNFR1 deficient mice survived the treatment. Conversely, TNFα treatment of wild type mice sensitized the animals to the toxic effects of an NH 4 + load. The protection of TNFα-deficient mice against an NH 4 + load was paralleled by decreased cerebral expression of NKCC1. According to the present observations, inhibition of TNFα formation and/or NKCC1 may be strategies to favorably influence the clinical course of hepatic encephalopathy.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-07640-8
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3