The impact of partial hepatectomy on oxidative state in the liver remnant - An in vivo swine model.
Previous studies on oxidative state after partial hepatectomy (PHx) report conflicting data on levels of glutathione (GSH) and are mainly presented in rodent models by methodology less sensitive than the present technologies. The current swine model presents GSH levels and the following genetic response post-PHx, utilizing an analytical platform more sensitive and precise than earlier available.



Twelve pigs were randomized to a PHx- and a control group (n=6 in each). The PHx group had a 60% hepatectomy. Serial in vivo liver biopsies during 12h of anaesthesia post-PHx were analyzed for GSH by liquid chromatography mass spectrometry (LC-MS/MS). Transcriptional alterations of genes (GS, GCLM, GCLC, GR, HGF, NFE2L2, TGFβ1) regulating GSH synthesis were measured by real-time PCR.



No difference was detected between the GSH levels in the PHx- and the control group during the experiment (P=0.247). Still, decreased gene expression of GS (P=0.026) and NFE2L2 (P=0.014) the first nine hours, and a decrease of TGFβ1 (P=0.029) the first seven hours post-PHx was seen in the liver remnant.



The results show that the liver has an extended capacity to maintain GSH homeostasis during major stress and parenchymal loss, even at the early onset of such trauma. This observation was not explained by increased expression of key genes in GSH pathways. Consequently, the results indicate an inherent compensatory capacity to maintain GSH homeostasis in the reduced organ.
Laboratory of Surgical Research, Institute of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Digestive Surgery, University Hospital North Norway, Tromsø, Norway. Electronic address: ase.florholmen-kjar@uit.no.
Åse
Å
Florholmen-Kjær
Department of Gastroenterology, University Hospital North Norway, Tromsø, Norway; Research group of Gastroenterology & Nutrition, UiT-The Arctic University of Norway, Tromsø, Norway.
Rasmus
R
Goll
Department of Laboratory Medicine, University Hospital North Norway, Tromsø, Norway.
Ole-Martin
OM
Fuskevåg
Laboratory of Surgical Research, Institute of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.
Ingvild Engdal
IE
Nygård
Research group of Gastroenterology & Nutrition, UiT-The Arctic University of Norway, Tromsø, Norway; Genomics Support Center Tromsø, UiT-The Arctic University of Tromsø, Norway.
Ruth H
RH
Paulssen
Laboratory of Surgical Research, Institute of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Digestive Surgery, University Hospital North Norway, Tromsø, Norway.
Arthur
A
Revhaug
Laboratory of Surgical Research, Institute of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Digestive Surgery, University Hospital North Norway, Tromsø, Norway.
Kim Erlend
KE
Mortensen
D000818:Animals; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism* / Q000601:surgery*; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D010084:Oxidation-Reduction; D013552:Swine
D005978:Glutathione
Glutathione; Liquid chromatography mass spectrometry/LC-MS/MS; Oxidative state; Partial hepatectomy; Swine