Linoleic acid, cis-epoxyoctadecenoic acids, and dihydroxyoctadecadienoic acids are toxic to Sf-21 cells in the absence of albumin

Abstract

Conversion of 12,13- cis-epoxyoctadecenoic acid (12,13-EOA) to 12,13-dihydroxyoctadecenoic acid (12,13-DHOA) by soluble epoxide hydrolase has been suggested to be a critical step in mediating the toxicity of epoxidized linoleic acid. The current study tests the hypothesis that low levels of albumin in the normal culturing media of Sf-21 cells can protect these cells from exposures to 12,13-EOA, but not 12,13-DHOA. In albumin-free media, Sf-21 cells exposed to 100 μM 12,13-EOA, and 12,13-DHOA for 1 min showed significant signs of mitochondrial dysfunction which led to cytotoxicity. The addition of bovine serum albumin (BSA) at a concentration (3 μM) found in normal serum-supplemented media protected Sf-21 cells exposed to 12,13-EOA, but not 12,13-DHOA while BSA (500 μM) fully protected Sf-21 cells exposed to these fatty acids. These data resolve previous discrepancies observed among in vitro models and help clarify our understanding of how these metabolites affect human health.