Modulation of adjuvant‐induced arthritis by dietary arachidonic acid in essential fatty acid‐deficient rats

Abstract

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.

Fatty acids, fatty acid analogues and their derivatives

“…The results showed that consumption of the average daily amount of AA without concurrent ingestion of linoleic acid did not alter the essential fatty acid deficient state. 565 The phospholipid AA level in the blood of human infants born at full term showed a continuous decrease over time when fed formula without AA or DHA as compared to breast-fed infants. 566 The effects of EPA and DHA in the diet (formula) of term infants [567][568][569][570] and infant rats 571 have been studied.…”

Dietary supplementation with arachidonic acid increases arachidonic acid content in paw, but does not affect arthritis severity or prostaglandin E2 content in rat adjuvant-induced arthritis model

“…To the best of our knowledge, there is one study in 1997 regarding the effects of ARA on AIA in essential fatty acid-deficient (EFAD) rats. ARA supplementation could increase the ARA content in EFAD and recover the suppressed inflammatory response in EFAD rats compared with normal rats [ 47 ]. This was an early and important report, but it does not necessarily reflect the situation for general arthritis.…”

“…The fatty acid profile in EFAD is quite abnormal, that is, ARA and LA are extremely reduced. Furthermore, Mead acid, which was clarified to have anti-inflammatory properties [ 48 – 50 ], was endogenously synthesized instead of ARA in EFAD and was reduced by ARA administration [ 47 ]. It is also reported that Mead acid is detected in articular cartilage of newborn animals, suggesting that Mead acid might have unknown roles in cartilage development [ 51 ].…”