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21-aminosteroid and 2-(aminomethyl)chromans inhibition of arachidonic acid-induced lipid peroxidation and permeability enhancement in bovine brain microvessel endothelial cell monolayers
Shi, Fenglin Cavitt, Jennifer Audus, Kenneth L.
Shi, Fenglin
Cavitt, Jennifer
Audus, Kenneth L.
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Abstract
Selected 21-aminosteroids (U74500A, U74006F, and U74389G) and a 2-(aminomethyl)chromans (U78517F) were tested for their efficacy in preventing arachidonate-induced lipid peroxidation and permeability alterations in brain microvessel endothelial cells (BMECs). The 21-aminosteroids and 2-(aminomethyl)chromans were effective in varying degrees in inhibiting (U74500A = U78517F> U74006F = U74389G) concentration- and time-dependent arachidonate-induced thiobarbituric acid reactive substances (TBARS) production by BMECs. Arachidonate produced a corresponding concentration-dependent increase in BMEC monolayer permeability to the membrane impermeant marker, sucrose. Pretreatment of BMEC monolayers with either the 21-aminosteroids or the 2-(aminomethyl)chromans completely blocked the arachidonate-induced increase in permeability to sucrose. Our results demonstrated that these membrane-associating antioxidants were particularly effective in preventing both arachidonic acid-induced lipid peroxidation and permeability changes in BMEC monolayers. However, concentrations of some antioxidants that only partially inhibited TBARS production, completely inhibited the arachidonic acid-induced enhancement in BMEC monolayer permeability. Therefore, arachidonic acid-induced effects on BMEC permeability were likely due in part to both lipid peroxidation and direct or indirect effects of the fatty acid on membrane integrity. This study provides further support for the application of primary cultures of BMECs as a useful in vitro system to evalulate mechanisms through which mediators of disease or injury states compromise blood-brain barrier integrity.
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Date
1995-09
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Elsevier
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Keywords
Free radicals, 21-Aminosteroids, 2-(Aminomethyl)chromans, Tirilazad, Arachidonic acid, Blood-brain barrier, Brain microvessel endothelial cells
Citation
Audus, K.L., Guillot, F.L., and Braughler, J.M. (1991) Evidence for 21-aminosteroid association with the hydrophobic domains in brain microvessel endothelial cells. Free Rad. Biol. Med. 11, 361-371. PMID: 1797623 http://dx.doi.org/10.1016/0891-5849(95)00049-4