Cholesterol photosensitised oxidation of horse meat slices stored under different packaging films

The effect of the type of packaging film (transparent vs. light-protecting red film) was evaluated on the formation of cholesterol oxidation products (COPs) in refrigerated horse meat slices stored in retail conditions under light exposure for 8 h. In meat wrapped with a transparent film, COPs increased from 233 (control) to 317 μg/g of fat, whereas the red film delayed cholesterol oxidation and offered protection against COPs formation, since COPs decreased from 173 (control) to 139 μg/g of fat after 8 h of light exposure. In addition, light opened the epoxy ring and led to the formation of triol, which was actually absent at T_0. A proper packaging film may represent a useful strategy to retard oxidative degradation in a light-sensitive, high pigment- and fat-containing food, such as horse meat.     

高植物甾醇玉米油改善高脂血症金黄地鼠的胆固醇代谢

植物甾醇具有调节胆固醇代谢的作用。为考察富含植物甾醇的玉米油是否仍然具备调节胆固醇代谢的作用,并初探其作用机制,通过高脂高胆固醇饮食诱导,建立金黄地鼠高脂血症模型,以橄榄油为对照,考察含17 000 mg/kg的高植物甾醇玉米油对金黄地鼠体重、血脂水平、主要脏器以及肠道菌群的影响。研究结果显示,高植物甾醇玉米油饮食干预10周后,金黄地鼠体重增长率下降40.9%,血总胆固醇和低密度脂蛋白胆固醇分别下降19.1%和45.5%,肝脏总胆固醇下降23.1%,肝脏指数下降8.5%,动脉硬化指数下降29.4%;但甘油三酯水平未见改善。高植物甾醇玉米油还可以改善金黄地鼠肠道菌群的丰度和结构,降低厚壁菌门/拟杆菌门的比例,并抑制脱硫杆菌等有害菌。因此,高植物甾醇玉米油可能通过抑制胆固醇吸收和调节肠道菌群,发挥降低体重增长率、促进胆固醇代谢健康、降低动脉硬化指数的作用。     

Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in rats

The hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (GG) root powder were examined in hypercholesterolaemic male albino rats. A 4-week administration of GG root powder (5 and 10 gm% in diet) to hypercholesterolaemic rats resulted in significant reduction in plasma, hepatic total lipids, cholesterol, triglycerides and plasma low-density lipoprotein and VLDL-cholesterol accompanied by significant increases in HDL-cholesterol levels. Furthermore, significant increases in fecal cholesterol, neutral sterols and bile acid excretion along with an increase in hepatic HMG-CoA reductase activity and bile acid production were observed in these animals. The root powder administration to hypercholesterolaemic rats also decreased hepatic lipid peroxidation with a concomitant increase in superoxide dismutase (SOD) and catalase activities and total ascorbic acid content. Thus, the hypocholesterolaemic and antioxidant effects of GG root appeared to be mediated via (i) accelerated cholesterol, neutral sterol and bile acid elimination through fecal matter with an increased hepatic bile acid production and (ii) improving the activities of hepatic SOD, catalase and increasing the ascorbic acid content. The normo-cholesterolaemic animals when fed with GG root powder at 10 gm% level, registered a significant decline in plasma lipid profiles and an increase in HDL-cholesterol content. The antioxidant status of these animals also was improved upon treatment.     

Identification of Correlative Shifts in Indices of Brain Cholesterol Metabolism in the C57BL6/Mecp2tm1.1Bird Mouse,a Model for Rett Syndrome

Rett syndrome (RS) is a pervasive neurodevelopmental disorder resulting from loss‐of‐function mutations in the X‐linked gene methyl‐Cpg‐binding protein 2 (MECP2). Using a well‐defined model for RS, the C57BL6/Mecp2^tm1.1Bird mouse, we have previously found a moderate but persistently lower rate of cholesterol synthesis, measured in vivo, in the brains of Mecp2^?/y mice, starting from about the third week after birth. There was no genotypic difference in the total cholesterol concentration throughout the brain at any age. This raised the question of whether the lower rate of cholesterol synthesis in the mutants was balanced by a fall in the rate at which cholesterol was converted via cholesterol 24‐hydroxylase (Cyp46A1) to 24S‐hydroxycholesterol (24S‐OHC), the principal route through which cholesterol is ordinarily removed from the brain. Here, we show that while there were no genotypic differences in the concentrations in plasma and liver of three cholesterol precursors (lanosterol, lathosterol, and desmosterol), two plant sterols (sitosterol and campesterol), and two oxysterols (27‐hydroxycholesterol [27‐OHC] and 24S‐OHC), the brains of the Mecp2 ^?/y mice had significantly lower concentrations of all three cholesterol precursors, campesterol, and both oxysterols, with the level of 24S‐OHC being ~20% less than in their Mecp2 ^+/y controls. Together, these data suggest that coordinated regulation of cholesterol synthesis and catabolism in the central nervous system is maintained in this model for RS. Furthermore, we speculate that the adaptive changes in these two pathways conceivably resulted from a shift in the permeability of the blood–brain barrier as implied by the significantly lower campesterol and 27‐OHC concentrations in the brains of the Mecp2^?/y mice.     

3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines

The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3‐deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X‐receptor (LXR) activation. The effects of 3dSB on ATP‐binding cassette transporter 1 levels and other LXR targets are similar to that of 25‐hydroxycholesterol, an LXR agonist. Unlike 25‐hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.     

An Ester of β-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans

In response to carbohydrate deprivation or prolonged fasting the ketone bodies, β‐hydroxybutyrate (βHB) and acetoacetate (AcAc), are produced from the incomplete β‐oxidation of fatty acids in the liver. Neither βHB nor AcAc are well utilized for synthesis of sterols or fatty acids in human or rat liver. To study the effects of ketones on cholesterol homeostasis a novel βHB ester (KE) ((R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate) was synthesized and given orally to rats and humans as a partial dietary carbohydrate replacement. Rats maintained on a diet containing 30‐energy % as KE with a concomitant reduction in carbohydrate had lower plasma cholesterol and mevalonate (?40 and ?27 %, respectively) and in the liver had lower levels of the mevalonate precursors acetoacetyl‐CoA and HMG‐CoA (?33 and ?54 %) compared to controls. Whole liver and membrane LDL‐R as well as SREBP‐2 protein levels were higher (+24, +67, and +91 %, respectively). When formulated into a beverage for human consumption subjects consuming a KE drink (30‐energy %) had elevated plasma βHB which correlated with decreased mevalonate, a liver cholesterol synthesis biomarker. Partial replacement of dietary carbohydrate with KE induced ketosis and altered cholesterol homeostasis in rats. In healthy individuals an elevated plasma βHB correlated with lower plasma mevalonate.     

高胆固醇膳食对兔动脉组织及其一氧化氮合成的影响

为研究高脂高胆固醇膳食对动脉壁内皮一氧化氮（ＮＯ）合成的影响，以高脂高胆固醇饲料喂饲雄性纯种新西兰兔８周后，通过定量逆转录多聚酶链式反应（ＲＴ－ＰＣＲ），观察高脂高胆固醇膳食对动脉组织一氧化氮合成酶（ＮＯＳ）基因表达影响。结果表明：高脂高胆固醇膳食８周后，内皮型（ＮＯＳ）ｍＲＮＡ表达下降、总ＮＯＳ活力减弱、血浆一氧化氮代谢产物（ＮＯＰ）水平降低（Ｐ＜０．０５）；内皮素（ＥＴ）水平上升。结果提示：高脂高胆固醇膳食引起高脂血症，可损害动脉内皮，降低ＮＯＳ的基因表达，抑制ＮＯ的合成     

Potato and soy peptides alter caecal fermentation and reduce serum non‐HDL cholesterol in rats fed cholesterol

We examined the effect of potato peptides (PPC) in rats fed a cholesterol‐enriched diet, in comparison with two cholesterol‐enriched diets containing soy peptides (SPC) or casein (CNC), and a cholesterol‐free diet containing casein (CN) for 4 weeks. The serum non‐high‐density lipoprotein (HDL) cholesterol level was lower in the PPC‐ (–18.39%) and SPC‐fed (–32.76%) groups (p <0.05) than in the CNC‐fed group at the end of the feeding period. The low‐density lipoprotein receptor mRNA level in the PPC‐fed group, and cholesterol 7α‐hydroxylase and scavenger receptor class B type 1 mRNA levels in the SPC‐fed group, were higher (p <0.05) than in the CN‐ and CNC‐fed groups. Faecal neutral sterol and caecal short‐chain fatty acid concentrations in the PPC‐ and SPC‐fed groups were higher (p <0.05) than in the CN‐ and CNC‐fed groups. The faecal total acidic sterol concentration was higher in the SPC‐fed group than in the CN‐ and PPC‐fed groups. Caecal anaerobe and Bifidobacterium populations were higher (p <0.05) in the PPC‐ and SPC‐fed groups than in the CN‐fed group. This study suggests that potato peptides, as soy peptides, alter caecal fermentation and steroid absorption and reduce the serum non‐HDL cholesterol level in rats fed cholesterol.     

Competitive Displacement of Clozapine from Plasma Proteins in Normolipidemic and Hyperlipidemic Plasma Samples: Clinical Implications

Objective, This study assesses whether competitive displacement of clozapine by warfarin affects clozapine's overall plasma distribution. Methods, Warfarin sodium was preincubated in normolipidemic and hyperlipidemic plasma samples in varying concentrations. Following the preincubation with warfarin, [³H]clozapine mixed with unlabeled clozapine was added to the plasma samples. The plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation, and clozapine distribution was determined. Results, When normolipidemic plasma was preincubated with various concentrations of warfarin, no significant redistribution of clozapine was noted among the various plasma lipoprotein fractions. However, in the case of the hyperlipidemic plasma, preincubating with warfarin did result in a significant redistribution of clozapine from the lipoprotein-deficient fraction to the very-low-density and low-density fractions of lipoproteins. Based on pharmacokinetic principles, the steady-state unbound concentration of clozapine in normolipidemic and hyperlipidemic plasma is not expected to change. Conclusion, Although no change in the steady-state unbound (active) concentration of clozapine would predict no change in clinical status, it is possible that this may only apply to the individuals with a normal lipid profile. We believe clozapine's association with lipoproteins (particularly triglycerides) may actually increase clozapine's effectiveness.