Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

Figure 1 Effect of losartan treatment in sirtuin 1 protein expression and SIRT1 activity parameters. A: Sirtuin 1 (SIRT1) protein expression; B: SIRT1 activity; C: NAD+/NADH levels; D and E: NAMPT and ac-FoxO1 protein expression in livers after 24 h of reperfusion. ^aP < 0.05 vs Sham, ^bP < 0.05 vs ROLT. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1 h of cold storage in University of Wisconsin solution; losartan + ROLT: same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.

Figure 2 Implication of losartan administration in mRNA (A) and protein levels of sirtuin 3 (B). ^aP < 0.05 vs Sham. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1 h of cold storage in University of Wisconsin solution; losartan + ROLT: Same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.

Figure 3 Role of losartan pretreatment in endoplasmic reticulum stress parameters. A: GRP78; B: IRE1α; C: p-eIF2 protein levels. ^aP < 0.05 vs Sham, ^bP < 0.05 vs ROLT. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1 h of cold storage in University of Wisconsin solution; losartan + ROLT: Same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.

Figure 4 Losartan administration regulates heat shock proteins expression. HO-1 (A) and HSP70 protein levels (B). ^aP < 0.05 vs Sham, ^bP < 0.05 vs ROLT. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1 h of cold storage in University of Wisconsin solution; losartan + ROLT: Same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.

Figure 5 Liver apoptosis in reduced-size orthotopic liver transplantation after losartan treatment. Protein levels of Caspase 12 (A) and Cleaved Caspase 3 (B). ^aP < 0.05 vs Sham, ^bP < 0.05 vs ROLT. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1h of cold storage in University of Wisconsin solution; losartan + ROLT: Same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.

Figure 6 Mitogen activated protein kinases modulation by losartan administration. Effect of losartan in p-ERK (A) and p-p38 protein expression (B). ^aP < 0.05 vs Sham. Sham: Liver harvested without transplantation; ROLT: Liver subjected to reduced-size orthotopic liver transplantation after 1 h of cold storage in University of Wisconsin solution; losartan + ROLT: Same as ROLT group, but with further administration of losartan 24 h and 1 h before the surgical procedure to both the donor and the recipient.