Triglyceride-rich lipoproteins improve survival when given after endotoxin in rats

Surgery. 1995 Jan;117(1):62-7. doi: 10.1016/s0039-6060(05)80231-4.

Abstract

Background: Triglyceride-rich lipoproteins have been shown to bind bacterial endotoxin and inhibit its activity in vitro and to protect animals from death when administered before a lethal injection of endotoxin. We now demonstrate that triglyceride-rich lipoproteins can neutralize the toxic effects of endotoxin already in circulation.

Methods: Rats were infused with a lethal dose of endotoxin, followed at various time intervals by an infusion of either mesenteric lymph containing nascent chylomicrons (1 gm chylomicron triglyceride/kg) or an equal volume of normal saline solution. Survival was measured at 48 hours. The experiment was then repeated, substituting the synthetic triglyceride-rich lipid emulsion (1 gm/kg) for chylomicrons. We also measured the clearance and tissue distribution of radioiodinated endotoxin in rats treated subsequently with chylomicrons or saline solution.

Results: Chylomicron infusions significantly improved survival when given up to 30 minutes after a lethal dose of endotoxin (p < 0.05). Chylomicrons accelerated endotoxin clearance from the blood and increased endotoxin uptake by the liver. The synthetic triglyceride-rich lipid emulsion significantly improved survival when given up to 15 minutes after a lethal dose of endotoxin (p < 0.05).

Conclusions: Triglyceride-rich lipoproteins and synthetic triglyceride-rich lipid emulsions significantly improve survival of rats when given after a lethal dose of endotoxin. Lipoprotein treatment accelerates endotoxin clearance to the liver, which may account for the observed protection. These data suggest a possible therapeutic role for triglyceride-rich lipoproteins or synthetic lipid emulsions in the treatment of the endotoxemia of gram-negative sepsis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chylomicrons / therapeutic use*
  • Endotoxins / blood
  • Escherichia coli
  • Fat Emulsions, Intravenous / therapeutic use
  • Iodine Radioisotopes
  • Lethal Dose 50
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Toxemia / drug therapy*
  • Toxemia / metabolism
  • Triglycerides / therapeutic use*

Substances

  • Chylomicrons
  • Endotoxins
  • Fat Emulsions, Intravenous
  • Iodine Radioisotopes
  • Triglycerides