AIM: To investigate a possible association between losartan and sirtuin 1(SIRT1) in reduced-size orthotopic liver transplantation(ROLT) in rats.METHODS: Livers of male Sprague-Dawley rats(200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 ℃ prior to ROLT.In an additional group,an antagonist of angiotensin Ⅱ type 1 receptor(AT1R),losartan,was orally administered(5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients.Transaminase(as an indicator of liver injury),SIRT1 activity,and nicotinamide adenine dinucleotide(NAD+,a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods.Protein expression of SIRT1,acetylated Fox O1(ac-Fox O1),NAMPT(the precursor of NAD+),heat shock proteins(HSP70,HO-1) expression,endoplasmic reticulum stress(GRP78,IRE1 a,p-e IF2) and apoptosis(caspase 12 and caspase 3) parameters were determined by Western blot.Possible alterations in protein expression of mitogen activated protein kinases(MAPK),such as p-p38 and p-ERK,were also evaluated.Furthermore,the SIRT3 protein expression and m RNA levels were examined.RESULTS: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group,as evidenced by the significant decreases in alanine aminotransferase(358.3 ± 133.44 vs 206 ± 33.61,P < 0.05) and aspartate aminotransferase levels(893.57 ± 397.69 vs 500.85 ± 118.07,P < 0.05).The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity(5.27 ± 0.32 vs 6.08 ± 0.30,P < 0.05).This was concomitant with increased levels of NAD+(0.87 ± 0.22 vs 1.195 ± 0.144,P < 0.05) the co-factor necessary for SIRT1 activity,as well as with decreases in ac-Fox O1 expression.Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters(GRP78,IRE1 a,p-e IF2) which was consistent with reduced levels of both caspase 12 and caspase 3.Furthermore,losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression.However,no changes were observed in protein or m RNA expression of SIRT3.Finally,the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration.CONCLUSION: The present study reports that losartan induces SIRT1 expression and activity,and that it reduces hepatic injury in a ROLT model. AIM: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. METHODS: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 ° C prior to ROLT. an additional group, an antagonist of angiotensin Ⅱ type 1 receptor (AT1R), losartan, was orally administered (5 mg / kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD +, a co-factor necessary for SIRT1 activity) were determined by biochemical methods. Protein expression of SIRT1, acetylated Fox O1 (ac-Fox O1), NAMPT (the precursor of NAD +), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1 a, peIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mito The activated protein kinases (MAPKs), such as p-p38 and p-ERK, also as.Furthermore, the SIRT3 protein expression and m RNA levels were examined.RESULTS: The present study said that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by a significant reduction in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P <0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P <0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P <0.05). This was concomitant with increased levels of NAD + (0.87 ± 0.22 vs 1.195 ± 0.144, P <0.05) factor necessary for SIRT1 activity, as well as with decreasing in ac-Fox O1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1 a, pe IF2) which was consistent with reduced levels of both caspase 12 an d caspase 3.Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. Although no changes were observed in protein or m RNA expression of SIRT3. Finaally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration .CONCLUSION: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces to hepatic injury in a ROLT model.