Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity
1 Department of Critical Care Medicine, University of Pittsburgh Medical School, USA
2 Department of Gastroenterology, Friendship Hospital, Capital Medical School, China
3 Department of Pathology, University of Tampere Medical School, Finland
4 Department of Intensive Care Medicine, University of Tampere Medical School, Finland
BMC Gastroenterology 2011, 11:125 doi:10.1186/1471-230X-11-125Published: 15 November 2011
Acetaminophen (APAP) overdose induces massive hepatocyte necrosis. Liver regeneration is a vital process for survival after a toxic insult. Since hepatocytes are mostly in a quiescent state (G0), the regeneration process requires the priming of hepatocytes by cytokines such as TNF-α and IL-6. Ringer's lactate solution (RLS) has been shown to increase serum TNF-α and IL-6 in patients and experimental animals; in addition, RLS also provides lactate, which can be used as an alternative metabolic fuel to meet the higher energy demand by liver regeneration. Therefore, we tested whether RLS therapy improves liver recovery after APAP overdose.
C57BL/6 male mice were intraperitoneally injected with a single dose of APAP (300 mg/kg dissolved in 1 mL sterile saline). Following 2 hrs of APAP challenge, the mice were given 1 mL RLS or Saline treatment every 12 hours for a total of 72 hours.
72 hrs after APAP challenge, compared to saline-treated group, RLS treatment significantly lowered serum transaminases (ALT/AST) and improved liver recovery seen in histopathology. This beneficial effect was associated with increased hepatic tissue TNF-α concentration, enhanced hepatic NF-κB DNA binding and increased expression of cell cycle protein cyclin D1, three important factors in liver regeneration.
RLS improves liver recovery from APAP hepatotoxicity.