Conjugated Linoleic Acid, cis-9,trans-11, Is a Substrate for Pulmonary 15-Lipoxygenase-1 in Rat

The objective of this study was to determine whether two of the major conjugated linoleic acid (CLA) isomers, cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12), are possible substrates for pulmonary 15-lipoxygenase-1 (15-LOX-1) and, therefore, they are also involved in the production of 13(S)-hydroxyoctadecadienoic acid [13(S)-HODE] in biological systems. 13(S)-HODE, a major bioactive metabolite of linoleic acid, is an important intracellular signal agent and is involved in cell proliferation and differentiation in various biological systems. Nordihydroguaiaretic acid (NDGA), a known LOX inhibitor, was used as a control for measuring 15-LOX-1 enzyme activity. It was found that c9,t11-CLA was 25% as active as linoleic acid as a substrate for 15-LOX-1; however, t10,c12-CLA was not a substrate for 15-LOX-1 as measured by 13(S)-HODE production. The authenticity of the production of 13(S)-HODE from c9,t11 as a substrate was established by isolation and cochromatography with pure standard on HPLC using non-radioactive and [14C]-c9,t11-CLA. Keywords: Carcinogenesis; conjugated linoleic acid; 13-hydroxyoctadecadienoic acid; lipoxygenase; lung; rat