Ultrastructural, Protein, and Lipid Changes in Liver Associated with Chlordecone Treatment of Mice

Pretreatment of mice with chlordecone (CD) reduced hepatic accumulationof a subsequent dose of [¹⁴C]CD without significantly changing[¹⁴C]CD biotransformation. To determine if CD-induced changesin hepatic [¹⁴C]CD accumulation were coincident with alteredcell composition, we examined the effects of CD on hepatic proteinand lipid content, on fatty acid profiles of liver and kidney,and on the ultrastructure of hepatocytes. SDS-polyacrylamidegel electrophoresis detected an apparent CD dose-related increasein a microsomal protein with a molecular weight of about 23kDa. Total liver or kidney lipid contents were not altered byCD but relative amounts of several hepatic fatty acids werechanged. CD caused marked hepatic mitochondrial swelling, increasedamounts of endoplasmic reticulum, apparently increased numbersof peroxisome-like structures, and decreased numbers of lipiddroplets in cytoplasm of hepatocytes. Numbers of lipid dropletswere not decreased in perisinusoidal fat storage cells. In addition,the numbers of cytoplasmic lipoprotein vesicles were apparentlyincreased in some hepatocytes. Overall these changes indicatedan increased hepatocyte secretory activity and suggested thatCD changed hepatocellular lipid transport, storage, and metabolismpathways.     

Alcohol-free red wine prevents arterial thrombosis in dietary-induced hypercholesterolemic rats: experimental support for the ''French paradox''

The concept of the 'French paradox' has been recently challenged. As it is difficult in a short period to produce direct clinical evidence of the protective effect of red wine on thrombosis, we evaluated such a possibility in an experimental model mimicking the conditions of the 'French paradox'. Normolipidemic rats (FNL) were fed a standard diet or a 2% cholesterol-rich-diet (Ch-rich-diet) for 5 months: the latter was given either alone (FNL + D) or in combination with 'alcohol-free' red wine (FNL + D + 5 W). Arterial thrombosis was measured as the occlusion time (OT) of an artificial prosthesis inserted into the abdominal aorta. Lipid levels, platelet adhesion to fibrillar collagen, factor VII (FVII) clotting activity and fibrinogen levels were also measured. Compared to animals fed a standard diet, Ch-rich diet induced in FNL rats a several-fold increase in lipids and FVII levels with a concomitant significant increase in both thrombotic tendency (shortening of the OT) and platelet adhesion. 'Alcohol-free' red wine supplementation almost completely reverted the prothrombotic effect of the Ch-rich-diet. Indeed, the OT was prolonged from 78 +/- 3 to 122 +/- 10 h (P < 0.01), while platelet adhesion to fibrillar collagen was reduced from 49 +/- 3.5% to 30 +/- 2.8%. Neither the increase in lipid levels induced by Ch-rich diet nor FVII or fibrinogen levels were modified by wine supplementation. In conclusion, in experimental animals, this study supports the concept of the 'French paradox' that regular consumption of wine (rather than alcohol) was able to prevent arterial thrombosis associated with dietary-induced hypercholesterolemia, an effect mediated by downregulation of platelet function.     

Synthesis and 19F spectra of tetra-L-alanine analogs containing selectively incorporated 3-fluoro-l-alanine residues

The synthesis of analogs of tetra-l -alanine containing 3-fluoro-l -alanine selectively incorporated at each position is described. The standard procedures in the literature used to couple l -alanine peptides together were often found to lead to undesired products, or elimination reactions when corresponding 3-fluoro-l -alanine peptide analogs were used. Several modified procedures have thus been developed for the synthesis of fluorine-substituted analogs. In addition, the pH-dependence of ¹⁹F n.m.r. spectra of 3-fluoro-l -alanine and the tetrapeptide analogs is presented.