Z Gastroenterol 2007; 45 - A3_08
DOI: 10.1055/s-2007-967844

The hepatoprotective effect of glycine is mediated through upregulation of proregenerative and downregulation of antiproliferative mediators in the liver

J Best 1, EM Niehues 2, T Benkö 3, M Trippler 1, U Rauen 3, G Gerken 1, JF Schlaak 4
  • 1Dept. of Gastroenterology and Hepatology, University Hospital of Essen, Essen
  • 2Department of General and Transplant Surgery, University Hospital of Essen, Essen
  • 3Institute of Biochemistry, University Hospital of Essen, Essen
  • 4Klinik für Gastroenterologie und Hepatologie, Uniklinikum Essen, Essen

Aims: Glycine pre-treatment has recently been shown to improve the outcome after liver transplantation and ischemia-reperfusion injury. Own data revealed that glycine is also hepatoprotective after subtotal (90%) hepatectomy (SH). However, only little is known about the molecular basis of this effect.

Methods: To further elucidate the molecular mechanisms responsible for the hepatoprotective effects of glycine we developed quantitative rt-PCRs and a customized inhouse cDNA gene array system for convenient multi-sample expression profiling for 120 genes of choice known to be involved in liver regeneration, apoptosis, inflammation, ischemia reperfusion injury and NFKB signalling. Male 6–8 weeks old Wistar rats (n=6/group) were subjected to SH. 5 days prior to resection animals of the test group were fed with glycine-enriched diet in contrast to control animals who received standard diet. 0h, 2h, 12h, 24h, 48h and 72h after surgery total RNA was isolated from liver tissue. The RNA samples were analyzed by customized gene arrays and quantitative rt-PCR. In addition, relevant clinical data (liver-body-weight ratio, liver function tests, survival) were recorded.

Results: Glycine treatment led to improved survival rates after resection which was associated with reduction of liver enzyme and bilirubin elevations. In glycine-treated animals a potent upregulation of proregenerative cytokines (IL–6, TNF-_, HGF) was observed by quantitative rt-PCR with a maximum directly after resection (HGF) or 48h after resection (IL–6, TNF-_). The LPS receptors CD14 and LBP were upregulated in glycine treated animals which is of particular interest with a possible involvement of the TLR system. In addition, the cDNA array analysis revealed that multiple genes including some genes involved in cell cycle regulation and growth control (PCNA, Pparg) or negative regulators of the TLR signalling pathway (IrakM) were downregulated by glycine treatment.

Discussion: These data indicate that a glycine pretreatment before subtotal liver resection results in improved clinical outcome. Our data suggest that this effect is mediated through hepatic upregulation of proregenerative and downregulation of antiproliferative genes and, at least in part, an activation of the TLR system.