Endotoxin alters serum-free choline and phospholipid-bound choline concentrations, and choline administration attenuates endotoxin-induced organ injury in dogs.
This study in dogs was performed to assess circulating choline status during endotoxemia and to determine whether choline administration can protect dogs from endotoxin-induced tissue injuries. Baseline serum-free and phospholipid-bound choline concentrations were 19.2 +/- 0.6 micromol/L and 3700 +/- 70 micromol/L, respectively. After intravenous endotoxin infusion, serum-free choline concentrations decreased by 14% to 49% (P < 0.05-0.001) at 2 to 6 h after 0.02 mg/kg endotoxin, and increased by 23% to 98% (P < 0.05-0.001) at 1 to 48 h after 1 mg/kg endotoxin. Serum phospholipid-bound choline concentrations increased by 19% to 27% (P < 0.05) at 12 to 24 h or by 18% to 53% (P < 0.05-0.001) at 1 to 48 h after 0.02 or 1 mg/kg endotoxin, respectively. The changes in serum-free and -bound choline levels in response to endotoxin were accompanied by dose- and time-related elevations in serum cortisol and biochemical markers for tissue injury and/or organ dysfunction. Intravenous administration of choline (20 mg/kg) 5 min before, and 4 and 8 h after endotoxin (1 mg/kg) attenuated endotoxin-induced elevations in serum alanine aminotransferase (P < 0.05-0.001), aspartate aminotransferase (P < 0.05-0.001), gamma-glutamyl transferase (P < 0.05-0.001), alkaline phosphatase (P < 0.05-0.001), lactate dehydrogenase (P < 0.05-0.001), myocardial creatine kinase (P < 0.001), urea (P < 0.05-0.01), creatinine (P < 0.05), uric acid (P < 0.01-0.001), and tissue necrosis factor-alpha (P < 0.001). Choline also attenuated alanine aminotransferase (P < 0.05-0.01), alkaline phosphatase (P < 0.05-0.01), lactate dehydrogenase (P < 0.05-0.01), creatine kinase (P < 0.05-0.001), myocardial creatine kinase (P < 0.05-0.001), and uric acid (P < 0.05-0.01), but failed to alter the serum urea, creatinine, aspartate aminotransferase, and gamma-glutamyl transferase responses to 0.02 mg/kg endotoxin. These data show that choline status is altered during endotoxemia and that choline administration diminishes endotoxin-induced tissue injury.
Ilcol
Yesim Ozarda
YO
Department of Biochemistry, Uludag University Medical School, The Central Clinical Chemistry Laboratory, 16059 Bursa, Turkey. yesim@uludag.edu.tr
Yilmaz
Zeki
Z
Ulus
Ismail H
IH
D000410:Alanine Transaminase / Q000096:biosynthesis / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002794:Choline / Q000737:chemistry* / Q000378:metabolism; D003402:Creatine Kinase / Q000096:biosynthesis; D003404:Creatinine / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000473:pathology; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014527:Uric Acid / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D016895:Culture Media, Serum-Free; D004731:Endotoxins; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; D000469:Alkaline Phosphatase; D002794:Choline; D006854:Hydrocortisone