Possible Interaction: Arachidonic Acid and Cyclosporine

“ CsA and LPS both enhance the release of labeled metabolites from cells labeled with arachidonic acid , but indomethacin only blocks the effect of LPS.”

“These differences are explained by mechanisms in which CsA promotes prostanoid synthesis through arachidonic acid release , and LPS promotes prostanoid synthesis through increased cyclooxygenase activity.”

“IL-1ß and IL-6 up-regulation, induced by CyA, was counteracted by the addition of EPA in both protocols; on the contrary, arachidonic acid (AA) magnified CyA the effects.”

“Circulating plasma concentrations of CsA and Tac inhibited CYP2C8 wild-type in vitro epoxidation of AA by 17 and 35%, respectively.”

“These results indicate that CsA inhibits arachidonic acid-stimulated production of PGI2 by HUVEC in a dose-dependent fashion beginning at concentrations comparable to the high end of the therapeutic range.”

“In fibroblasts stimulated with thapsigargin, which induces MPTP formation by a direct effect on mitochondria, LDH and arachidonic acid release were blocked by CsA and 1-oleoyl-2-acetyl-sn-glycerol but not by pyrrophenone or EGTA.”

“Unlike pyrrophenone, the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol and CsA blocked cell death and arachidonic acid release not by preventing mitochondrial calcium uptake but by inhibiting MPTP formation.”

“… cyclosporin A (… arachidonic acid (AA) to 20-HETE (93 ± 6%, P < 0.05), increased systolic blood pressure (SBP), reduced the urinary excretion of nitrite (53 ± 8%, P < ….05) and sodium nitroprusside (SNP; 56 ± 13%, P < 0.05) in the renal preglomerular vessel treated with indomethacin and NO synthase inhibitor.”

“All these effects of arachidonic acid could be prevented by cyclosporin A but not by the phospholipase A2 inhibitor aristolochic acid.”

“ Arachidonic acid omega-hydroxylation activity was also induced 2-fold by treatment with CsA for 17 days.”

“These data suggest that CsA increased arachidonic acid omega-hydroxylation activity by the induction of CYP4A2.”

“In addition, CSA treatment resulted in i) a reduced acylation of arachidonic acid into medullary phospholipids by 25% and into medullary and cortical triglycerides by 33 and 27%, respectively, and ii) an increase in cortical and medullary triglycerides.”

“This inhibitory effect might be explained by the previous findings of others, that CSA inhibits phospholipase A2 activity, thereby decreasing arachidonic acid production, the rate-limiting step in PG synthesis.”