BACKGROUND: Acute liver failure is associated with a marked depletion of intrahepatic adenosine 5'-triphosphate (ATP), a compound required for the maintenance of hepatic function and enhanced hepatic regeneration. AIM: The aim of this study was to test the safety and efficacy of exogenous ATP at various doses in a rat model of acute liver failure. METHODS: Adult male Sprague-Dawley rates (n = 56) received an intraperitoneal dose (1.0 g/kg) of the potent hepatotoxin D: -galactosamine (D: -galN). Thereafter, rats were divided into groups that received saline (n = 18), low (n = 8), moderate (n = 18) or high (n = 12) doses of ATP for 7 days. RESULTS: There was an inverse correlation between ATP dose and survival such that rats treated with low dose ATP had the highest survival rate (50%) compared to moderate (39%) and high (17%) dose treated groups. However, survival in all treated groups was similar (P = 0.085) to that of controls (45%). Liver biochemistry, regenerative activity and ATP levels were similar in the highest survival group (low dose ATP) versus controls. CONCLUSION: These findings suggest that exogenous ATP does not improve and indeed at high doses may impair survival in rats with acute liver failure. Further studies involving a wider range of ATP doses and different routes and frequency of ATP administration are required to determine whether exogenous ATP has therapeutic value in the treatment of acute liver failure.
BACKGROUND:Acute liver failure is associated with a marked depletion of intrahepatic adenosine 5'-triphosphate (ATP), a compound required for the maintenance of hepatic function and enhanced hepatic regeneration. AIM: The aim of this study was to test the safety and efficacy of exogenous ATP at various doses in a rat model of acute liver failure. METHODS: Adult male Sprague-Dawley rates (n = 56) received an intraperitoneal dose (1.0 g/kg) of the potent hepatotoxin D: -galactosamine (D: -galN). Thereafter, rats were divided into groups that received saline (n = 18), low (n = 8), moderate (n = 18) or high (n = 12) doses of ATP for 7 days. RESULTS: There was an inverse correlation between ATP dose and survival such that rats treated with low dose ATP had the highest survival rate (50%) compared to moderate (39%) and high (17%) dose treated groups. However, survival in all treated groups was similar (P = 0.085) to that of controls (45%). Liver biochemistry, regenerative activity and ATP levels were similar in the highest survival group (low dose ATP) versus controls. CONCLUSION: These findings suggest that exogenous ATP does not improve and indeed at high doses may impair survival in rats with acute liver failure. Further studies involving a wider range of ATP doses and different routes and frequency of ATP administration are required to determine whether exogenous ATP has therapeutic value in the treatment of acute liver failure.
Authors: C S Lay; Y T Tsai; C W Kong; F Y Lee; T T Chang; H C Lin; C M Yang; S D Lee; B N Chiang; K J Lo Journal: Clin Pharmacol Ther Date: 1988-10 Impact factor: 6.875
Authors: Ian R Corbin; Richard Buist; Vyacheslav Volotovskyy; Jim Peeling; Manna Zhang; Gerald Y Minuk Journal: Hepatology Date: 2002-08 Impact factor: 17.425
Authors: Hendrik J Agteresch; Sjaak A Burgers; Ate van der Gaast; J H Paul Wilson; Pieter C Dagnelie Journal: Anticancer Drugs Date: 2003-09 Impact factor: 2.248