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Exogenous Adenosine 5′-triphosphate does not Improve Survival in Rats with Acute Liver Failure

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Abstract

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.

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Acknowledgments

The authors would like to thank Mrs. S. Zdanuk for her prompt and accurate typing of the manuscript. Ms. Becker is the recipient of an INSERC Graduate Student Award.

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Authors and Affiliations

  1. Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada

    Erin P. Becker & Gerald Y. Minuk

  2. Section of Hepatology, Departments of Medicine, University of Manitoba, John Buhler Research Centre, 803-715 McDermot Avenue, Winnipeg, MB, Canada, R3E 3P4

    DongFeng Sun & Gerald Y. Minuk

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  1. Erin P. Becker
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  2. DongFeng Sun
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  3. Gerald Y. Minuk
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Correspondence to Gerald Y. Minuk.

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Becker, E.P., Sun, D. & Minuk, G.Y. Exogenous Adenosine 5′-triphosphate does not Improve Survival in Rats with Acute Liver Failure. Dig Dis Sci 53, 794–798 (2008). https://doi.org/10.1007/s10620-007-9940-z

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  • DOI: https://doi.org/10.1007/s10620-007-9940-z

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