CTEM and HVEM of Rat Liver After Dosing With MDL 18719, A Serum Lipid Lowering Agent

Abstract

MDL-18719 which is (E)-3-[5-(1-oxododecyl)-2-furanyl]-2-propenoic acid has been shown to reduce serum cholesterol and triglycerides when administered orally to test animals. It is structurally related to RMI-14,514 a hypolipidemic drug reported to cause quantitative and qualitative alterations of hepatocellular peroxisomes (microbodies) when administered to rats.Male Sprague-Dawley rats were treated for 13 days with 0.125% MDL-18719 in the diet then sacrificed. A portion of the liver from each animal was immersed in cold 0.15 M cacodylate-buffered 4% paraformaldehyde, 0.05% dinitrodifluorobenzene, 4% glutaraldehyde fixative solution. Tissue sections 50μ thick were prepared and treated in catalase localization medium. The specimens were osmicated, dehydrated in graded acetones and embedded in epoxy resin. Additional liver specimens from the same rats were prepared in a similar fashion omitting the enzyme localization step. Thin sections were prepared for conventional transmission EM (CTEM), and 0. 5. thick sections were cut for high voltage EM (HVEM).