Basic Study
Copyright ©The Author(s) 2015.
World J Gastroenterol. Feb 14, 2015; 21(6): 1765-1774
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1765
Figure 1
Open in New Tab Full Size Figure Download Figure
Figure 1 Alanine aminotransferase levels (A) and hepatic glutamate dehydrogenase (B) in plasma after 24 h of reperfusion. Sham: Liver harvested without transplantation; IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 M Trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1. ALT: Alanine aminotransferase; GLDH: Glutamate dehydrogenase.
Figure 2
Open in New Tab Full Size Figure Download Figure
Figure 2 NAMPT protein expression (A), NAD+/NADH levels (B), SIRT1 (C), ac-FoxO1 (D) and ac-p53 (E) protein expression in livers after 24 h of reperfusion. Sham: Liver harvested without transplantation, IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 mol/L trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1. NAMPT: Nicotinamide phosphoribosyltransferase; NAD+: Nicotinamide adenine dinucleotide; SIRT1: Sirtuin 1; FoxO1: Forkhead box-containing protein O 1; NADH: Nicotinamide adenine dinucleotide.
Figure 3
Open in New Tab Full Size Figure Download Figure
Figure 3 Malondialdehyde (A) and HSP70 protein levels (B) in livers after 24 h of reperfusion. Sham: Liver harvested without transplantation; IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 mol/L trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1. MDA: Malondialdehyde.
Figure 4
Open in New Tab Full Size Figure Download Figure
Figure 4 Protein levels of p-AMPK (A), p-mTOR/mTOR (B) and p-p70S6k (C) in livers after 24 h of reperfusion. Sham: Liver harvested without transplantation; IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 mol/L trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1.
Figure 5
Open in New Tab Full Size Figure Download Figure
Figure 5 Protein expression of beclin-1 (A) and LC3B (II)/(I) (B) in livers after 24 h of reperfusion. Sham: Liver harvested without transplantation; IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 mol/L trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1.
Figure 6
Open in New Tab Full Size Figure Download Figure
Figure 6 Protein levels of pERK (A) and p-p38 (B) in livers after 24 h of reperfusion. Sham: Liver harvested without transplantation; IGL-1: Liver transplanted after 8 h of cold storage in IGL-1 solution; IGL-1 + TMZ: Liver transplanted after 8 h of cold storage in IGL-1 solution with 10-6 mol/L trimetazidine (TMZ). aP < 0.05 vs Sham; cP < 0.05 vs IGL-1.
Figure 7
Open in New Tab Full Size Figure Download Figure
Figure 7 Schematic model of the protective effect of sirtuin 1 against ischemia-reperfusion injury associated to rat orthotopic liver transplantation. Trimetazidine (TMZ) addition to IGL-1 promotes NAMPT expression and enhances NAD+ levels, which in turn provokes SIRT1 up-regulation. SIRT1 contributes to decreased hepatic injury by inhibiting mitochondrial damage and oxidative stress, activating autophagic pathway and by enhancing p-ERK and decreasing p-p38 protein expression. SIRT1: Sirtuin 1; IRI: Ischemia-reperfusion injury; OLT: Orthotopic liver transplantation.