Hypercholesterolemia and tissue-specific differential mRNA expression of type-1 5'-iodothyronine deiodinase under different selenium status in rats

Type-1 5'-iodothyronine deiodinase (5'-DI) is responsible for conversion of T4 to T3. Selenium (Se) is an integral part of this enzyme. Keeping in view the strong association between atherosclerosis and hypothyroidism, the present study examined the behavior of 5'-DI in liver, aorta and thyroid during hypercholesterolemia following different Se status, i.e., Se deficiency (0.02ppm), adequate (0.2ppm) and excess dose (1ppm) in SD male rats. Animals were fed a control or high-cholesterol diet (2%) for 1 and 2 months. 5'-DI activity and mRNA expression was measured by RIA and RT-PCR respectively. In liver and aorta, 5'-DI expression significantly decreased with the Se-deficient and the high-cholesterol diet. The trend was opposite in thyroid, i.e., mRNA expression increased significantly during selenium deficiency and with a high-cholesterol feeding. But with 1ppm Se supplementation, the 5'-DI expression increased in all the three tissues. The present study indicates that hypercholesterolemia along with selenium deficiency is co-responsible for differential regulation of 5'-DI enzyme in thyroidal vs. extrathyroidal tissues. Distinct regulation of 5'-DI in the thyroid reflects the clinical importance of this selenoprotein during hypercholesterolemia as this enzyme is essential for T3 production, which further has a vital role in the maintenance of lipid metabolism.

Lipid peroxidation in different tissues: effect of high cholesterol and fish oil in the diet.

Malonyldialdehyde was measured in erythrocytes, aorta and spleen on feeding mice with high cholesterol diet in presence and absence of fish oil. Mice were grouped as: Group I: Control laboratory diet Group II: 0.16% cholesterol (sunflower oil) Group III: 1.16% cholesterol (sunflower oil) Group IV: 1.16% cholesterol (fish oil) After 7 weeks on their respective diets, erythrocytic, and splenic MDA levels were significantly higher in group III compared to controls. Also, MDA levels in aorta and spleen showed a significant increase in group IV males compared to group III males. However in group IV the erythrocyte MDA levels were almost equal to that in controls. This suggests that high cholesterol diet increases lipid peroxidation in erythrocytes, spleen and aorta. Addition of fish oil in the diet further increases lipid peroxidation in aorta and spleen, but not in the erythrocytes.

Inhibition of expression of P-selectin by antioxidant in cholesterol-fed rats

Butylated hydroxytoluene (BHT) can inhibit experimental atherosclerosis in animals. Although the agent is an antioxidant, the exact mechanism of the reaction in atherosclerosis is still unknown. To investigate the effects of BHT on expression of P-selectin (PADGEM, GMP-140), intercellular adhesion molecule-1 (ICAM-1) and class II MHC (Ia) antigen, we proposed an experiment on rats. Male rats (n=18 per group) were fed either a normal cholesterol control diet, a normal cholesterol diet containing 0.5% BHT (BD), a high cholesterol diet containing 1.5% cholesterol and 0.1% sodium cholate (CD), or the CD diet containing 0.5% BHT (BCD). Rats were sacrificed after 3 days, and after 1, 2, 4, 10, and 17 weeks of dietary treatment. Although there was no gross or light microscopic atherosclerotic lesions, scanning electron microscopy revealed monocytic adhesion to aortic endothelium and mild endothelial injuries in CD and BCD groups. Immunohistochemically, the addition of BHT to a high cholesterol diet inhibited P-selectin expression but not in ICAM-1 and Ia antigen. These findings suggest that in rats, high cholesterol diets induce expression of ICAM-1, P-selectin and Ia antigen. In addition, the antiatherogenic effect of BHT may play a role in the inhibition of P-selectin.

Influência do grau de saturaçäo dos ácidos graxos da dieta e do estado alimentar sobre a esterificaçÝo do colesterol e sua transferência entre lipoproteínas no plasma / Influence saturation degree of fatty acid of diet and fasting state about cholesterol esterification and its transfer among lipoproteins in plasma

Mulheres portadoras de hipercolesterolemia moderada (n=19) foram submetidas, por 2 períodos de 3 semanas cada um, a uma dieta rica em ácidos graxos saturados (SAT) ou poliinsaturados (POLI). A escolha da dieta para iniciar o estudo foi aleatória, tendo sido trocada no período subsequente. Estas pacientes foram estudadas em jejum e no período alimentar (após a ingestÝo de sobrecarga de gordura, contendo 40g de gordura por 'm POT. 2' de superfície corporal). Foram dois os tipos de refeiçÝo-teste preparados de forma liofilizada: um com gordura saturada e outro com poliinsaturada. Cada paciente recebeu no teste a refeiçÝo com o mesmo tipo de gordura da dieta à qual já estava sendo submetido. A velocidade de esterificaçÝo do 'ANTPOT 14 C'-colesterol medida nas HDL (obtidas através da precipitaçÝo de lipoproteínas contendo apoB - VLDL+LDL com sulfato de dextrana/Mg'Cl IND. 2') foi idêntica nas duas dietas e aumentou igualmente no período alimentar. A transferência de 'ANTPOT 14 C'-colesteril-éster das HDL para VLDL+LDL foi, também, semelhante nas duas dietas, mas aumentou no período alimentar. A sobrecarga oral de gordura provocou elevaçÝo dos triglicérides plasmáticos com as duas dietas estudadas, sendo que o aumento foi significativamente maios com a dieta poliinsaturada. Os valores de apoB nÝo foram alterados comparando-se o jejum ao período alimentar. A saturaçÝo dos ácidos graxos também nÝo modificou os níveis plasmáticos de apoB. A transferência de '14 ANTPOT. C'-colesteril-éster corrigida pelos valores plasmáticos de apoB foi semelhante com as duas dietas. No período alimentar a transferência de 'ANTPOT.14 C'-colesteril-éster das HDL foi menor com a dieta POLI do que com a SAT, quando relacionado àtrigliceramida. Consequentemente, a configuraçÝo espacial das moléculas de triglicérides nas lipoproteínas contendo apoB restringe a concentraçÝo de colesteril-éster captada das HDL na dieta POLI. Esta conclusÝo é reforçada pelo fato de a concentraçÝo da proteína de transferência de colesteril-éster (CETP), medida por radioimunoensaio, similar com as duas dietas, tenha sido maior com a dieta poliinsaturada no período alimentar. Conclui-se, portanto, que o aumento da concentraçÝo de triglicérides, induzido pela alimentaçÝo no período alimentar, influenciou mais a velocidade de transferência de '14 ANTPOT. C'-colesteril-éster, mediada pela CETP, do que a composiçÝo dos ácidos graxos da dieta

Efecto comparativo de aceites de origen vegetal o marino y suplementación de colesterol en lípidos de plasma e hígado de rata / Comparative effect of vegetable or marine oils and cholesterol supplementation on plasma and liver lipids of the rat

Los aceites poseen una composición acil grasa característica, responsable de muchos de sus efectos biológicos, que pueden modificarse por la ingestión concomitante de colesterol. En el estudio se evaluó el efecto de la ingestión de aceites de maíz, avellana y pescado, y la suplementación con colesterol, sobre los niveles de lípidos plasmáticos y hepáticos. Ratas macho se alimentaron con dieta que contenía 15 por ciento de aceite, sin/con 1 por ciento colesterol, durante 20 días. El grupo con avellanas exhibió la mayor concentración plasmática de colesterol, p<0,001, en tanto que el grupo con aceite de pescado presentó los niveles más bajos, p<0,001. El grupo con maíz/colesterol exhibió menos concentración de HDL, p<0,001, la cual aumentó en el grupo con aceite de pescado/colesterol. El peso del hígado fue mayor en el grupo con maíz/colesterol, p<0,001. El colesterol indujo un incremento de los lípidos hepáticos en los grupos con aceites vegetales. Los lípidos hepáticos fueron más bajos al ingerir aceite marino/colesterol, p<0,001. Los resultados indican que el aceite de pescado indujo los niveles más bajos de lípidos en plasma, en tanto que el de avellana es hipercolesterolémico, mostrando estrecha relación entre las grasas dietarias (ácidos grasos y colesterol) y los lípidos plasmáticos y hepáticos

Neutral sterol excretions in rats fed skim milk and skim milk yogurt diets.

Acceleration of cholesterol catabolism (through feces) has been proposed as one of the mechanisms for the hypocholesterolemic effect of dairy products. This study examined the effects of feeding two milk products (skim milk and skim milk yogurt) on fecal neutral sterol excretions in rats. Six groups of nine rats each were fed iso-caloric Chow-based diets containing water, 45% skim milk (SM), or 45% skim milk yogurt (SMY), without or with cholesterol. The results indicate that both SM and SMY increased the excretion of total neutral sterols under hyperlipemic conditions. The SMY diet (with cholesterol) also increased the excretion of coprostanol, a bacterial metabolite.