title: Ringer's lactate improves liver recovery in a murine model of acetaminophen toxicity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  RLS improves liver recovery from APAP hepatotoxicity.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh Medical School, USA. bobyangr@yahoo.com
authors.forename: Runkuan
authors.initials: R
authors.lastname: Yang
authors.forename: Shutian
authors.initials: S
authors.lastname: Zhang
authors.forename: Henri
authors.initials: H
authors.lastname: Kajander
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhu
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Koskinen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Tenhunen
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000628:therapy*; D019938:Cyclin D1 / Q000378:metabolism; D062787:Drug Overdose / Q000628:therapy; D007552:Isotonic Solutions / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D000077325:Ringer's Lactate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D007552:Isotonic Solutions; D016328:NF-kappa B; D000077325:Ringer's Lactate; D014409:Tumor Necrosis Factor-alpha; D019938:Cyclin D1; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
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