Effect of intravenous lipid emulsions enriched with gamma-linolenic acid on plasma n-6 fatty acids and prostaglandin biosynthesis after burn and endotoxin injury in rats.
OBJECTIVE
To study the effect of intravenous lipid emulsions enriched with gamma-linolenic acid on plasma fatty acids and series-2 prostaglandins to determine if the slow conversion of linoleic acid by delta-6-desaturase to gamma-linolenic acid could be bypassed to provide substrate for the formation of dihomo-gamma-linolenic acid, the immediate precursor for series-1 prostaglandins, in control and injured rats. Dihomo-gamma-linolenic acid can also compete with arachidonic acid for oxidative metabolism by cyclooxygenase to modulate series-2 prostaglandin biosynthesis.


METHODS
Prospective, randomized, controlled, double-blind study.


METHODS
Research laboratory at a university medical center.


METHODS
Thirty-three control and thirty-one injured male Sprague-Dawley rats were randomized into one of four parenteral dietary treatment groups.


METHODS
Rats were injured by the combined actions of a 30% body surface area full-thickness skin burn and a nonlethal injection of endotoxin (1 mg/kg ip). The rats were parenterally fed 200 kcal/kg/day, 1.5 g nitrogen/kg/day, and 30% of nonprotein calories as lipid (20% soybean lipid emulsion enriched with 2.7%, 4.4%, or 6.1% gamma-linolenic acid derived from borage oil) for 3 days. Control rats were treated similarly but were not injured. A 20% soybean/safflower oil lipid emulsion was used as the control diet (0% gamma-linolenic acid). Plasma was analyzed on day 3 to determine the concentrations of total fatty acids, thromboxane B2, 6-keto-prostaglandin F1 alpha, and bicyclo-prostaglandin E.


RESULTS
Parenteral nutrition with 2.7%, 4.4%, and 6.1% gamma-linolenic acid increased the plasma percentages (mol%) of gamma-linolenic acid and dihomo-gamma-linolenic acid in a dose-dependent fashion in control and injured rats. Supplementation with gamma-linolenic acid did not increase the plasma percentage of arachidonic acid as compared with the 0% gamma-linolenic acid lipid emulsion in control and injured rats. The ratio of dihomo-gamma-linolenic acid to arachidonic acid was significantly increased in response to 4.4% and 6.1% gamma-linolenic acid in both the control and injured groups. The plasma ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha was substantially reduced with gamma-linolenic acid compared with 0% gamma-linolenic acid in injured rats. Bicyclo-prostaglandin E concentration was significantly higher with 2.7% gamma-linolenic acid in injured rats. Injured rats were protein catabolic, as evidenced by a net negative nitrogen balance and loss of body mass compared with controls, but neither group showed overt signs of intolerance to the diets.


CONCLUSIONS
Supplementation of parenteral nutrition with gamma-linolenic acid had the following effects: a) increased plasma gamma-linolenic acid, dihomo-gamma-linolenic acid, and bicyclo-prostaglandin E; b) increased the plasma ratio of dihomo-gamma-linolenic acid to arachidonic acid; and c) favorably reduced the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha in injured rats. These results reflect the potential capacity of gamma-linolenic acid-enriched lipid emulsions to have the following actions: a) to increase dihomo-gamma-linolenic acid, which is the fatty acid precursor of the antiaggregatory, anti-inflammatory eicosanoid, prostaglandin E1; and b) to modulate arachidonic acid-derived series-2 prostaglandins after injury.
Karlstad
M D
MD
Department of Anesthesiology, Graduate School of Medicine, University of Tennessee Medical Center, Knoxville 37920.
DeMichele
S J
SJ
Leathem
W D
WD
Peterson
M B
MB
D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000097:blood / Q000453:epidemiology / Q000628:therapy*; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000633:toxicity*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D008297:Male; D010288:Parenteral Nutrition; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis; D013312:Stress, Physiological / Q000097:blood / Q000453:epidemiology / Q000628:therapy; D017965:gamma-Linolenic Acid / Q000008:administration & dosage*
D004731:Endotoxins; D005217:Fat Emulsions, Intravenous; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D011453:Prostaglandins; D017965:gamma-Linolenic Acid