title: Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: involvement of the peripheral nicotinic acetylcholine receptors.
abstract: We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.
authors.affiliation: Department of Biochemistry (Medical School), Uludag University, Bursa, Turkey. yesim@uludag.edu.tr
authors.forename: Yesim Ozarda
authors.initials: YO
authors.lastname: Ilcol
authors.forename: Zeki
authors.initials: Z
authors.lastname: Yilmaz
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Ulus
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D002794:Choline / Q000494:pharmacology* / Q000627:therapeutic use; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D018738:Hexamethonium / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy; D014280:Triglycerides / Q000097:blood
chemical_list: D004731:Endotoxins; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D018733:Nicotinic Antagonists; D010743:Phospholipids; D011978:Receptors, Nicotinic; D014280:Triglycerides; D018738:Hexamethonium; D003566:Cytidine Diphosphate Choline; D001285:Atropine; D002784:Cholesterol; D002794:Choline