Liver: Cirrhosis, Fibrosis, And Portal Hypertension

Digestive Diseases and Sciences

, Volume 41, Issue 11, pp 2204-2212

Effect of ethanol on adenosine triphosphate, cytosolic free calcium, and cell injury in rat hepatocytes

Time course and effect of nutritional status
  • Antonio GasbarriniAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , André B. BorleAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , Paolo CaraceniAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , Alessandra ColantoniAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , Hassan FarghaliAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , Franco TrevisaniAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , Mauro BernardiAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute
  • , David H. van ThielAffiliated withFrom the Patologia Medica, Catholic UniversityDepartment of Physiology, University of PittsburghPatologia Medica I, University of BolognaOklahoma Transplantation Institute

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Abstract

The events implicated in the early phases of acute ethanol-induced hepatocyte injury and their relation with the nutritional status of the liver are not clearly defined. We aimed to determine the effect of ethanol on ATP and cytosolic free Ca2+ in hepatocytes isolated from fed or fasted rats. Cell injury was assessed by LDH release and trypan blue uptake, ATP by [31P]NMR spectroscopy, and cytosolic free Ca2+ with aequorin. In control conditions, cells from fasted animals had a lower ATP level (−52%) and a higher cytosolic free Ca2+ (+101%) than did those isolated from fed animals. Ethanol caused a dose-dependent cell injury in both groups. At all ethanol doses, greater damage occurred when using hepatocytes isolated from fasted rats. In both groups, a dose-dependent decrease in ATP content and a rise in cytosolic free Ca2+ were seen. The magnitude of these changes were significantly greater in the fasted group. In conclusion, these data showed that fasting affects the energy status and cytosolic free calcium level in hepatocytes; ethanol causes a dose-dependent cell injury that occurs in association with a fall in ATP and a rise in cytosolic free Ca2+ levels. The nutritional status of an animals is an important determinant of the severity of ethanol-induced damage to liver cells.

Key words

hepatocyte ethanol cytosolic free calcium lactate dehydrogenase