Modulation of adjuvant-induced arthritis by dietary arachidonic acid in essential fatty acid-deficient rats.
Controlled feeding of linoleic acid (LA) or arachidonic acid (AA) to essential fatty acid-deficient (EFAD) rats was used to define the relationship between dietary AA and the inflammatory response evoked during adjuvant-induced arthritis. Based on energy percentage, EFAD rats were fed AA at the human daily equivalent (1x; 5.5 mg/day) or 10 times that amount (10x; 55 mg/day) or, alternatively 0.5x of LA (273 mg/day). Feeding of 0.5x LA restored the plasma level of AA to that in chow-fed controls. In contrast, feeding of 1x AA only partially restored the plasma level of AA; 10x AA was required to fully replete AA. In parallel to the degree of repletion of AA in plasma, there were accompanying decreases in the levels of palmitoleic acid, oleic acid, and Mead acid. Compared to rats fed the standard laboratory chow diet (Control), edema in the primary hind footpads was decreased by 87% in EFAD, 71% in EFAD + 1x AA, 45% in EFAD + 10x AA, and 30% in EFAD + 0.5x LA. The decrease in edema in the footpads of EFAD rats was nearly identical to the decrease in edema in the footpads of Control rats dosed with indomethacin. Hind footpad edema correlated with the final AA plasma level and eicosanoid levels extracted from hind footpad tissue, but not with neutrophil infiltration. The data showed that 0.5x LA and 10x AA, but not 1x AA, could quickly replete AA, accompanied by the synthesis of AA-derived eicosanoids and restoration of edema. These results suggest that in humans consumption of the average daily amount of AA without concurrent ingestion of LA would not alleviate an EFAD state.
Chinn
K S
KS
G.D. Searle, St. Louis, Missouri 63198, USA.
Welsch
D J
DJ
Salsgiver
W J
WJ
Mehta
A
A
Raz
A
A
Obukowicz
M G
MG
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000178:diet therapy* / Q000378:metabolism; D001835:Body Weight; D004041:Dietary Fats / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D002149:Energy Intake; D005227:Fatty Acids / Q000097:blood; D005228:Fatty Acids, Essential / Q000172:deficiency*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
D004041:Dietary Fats; D015777:Eicosanoids; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D016718:Arachidonic Acid; D019787:Linoleic Acid; D009195:Peroxidase; D007213:Indomethacin