Cisatracurium Besylate mg br Materials and Methods br Result

Materials and Methods
Results
Discussion Rats have a low cholesterol Cisatracurium Besylate mg rate compared to humans. Thus, the inclusion of cholic acid in a cholesterol diet has been widely used to improve cholesterol absorption and induce hypercholesterolemia in rats for studying human cholesterol metabolism [29], [30], [31]. In agreement with these previous reports, rats fed the diet without cholic acid had a very low cholesterol absorption rate, approximately 16%. When 0.5% cholic acid was added to the diet, cholesterol absorption rate was increased to about 60%, becoming close to that in humans and hamsters [13], [26]. More importantly, the cholesterol profiles of rats without supplementation of cholic acid were quite different from that of humans and by contrast became similar when cholic acid was provided [13]. Using this rat model, we demonstrated that BBR significantly inhibited the intestinal cholesterol absorption, leading to the large decreases of plasma total and nonHDL cholesterol levels. An indirect support has been provided by a recent study showing that BBR promoted the excretion of neutral sterols [32]. Strong correlations between cholesterol absorption rates and plasma total or nonHDL cholesterol levels provide further support that BBR lowered blood cholesterol levels through inhibiting the intestinal absorption. This is another mechanism that is distinct from the previously reported enhancement of LDLR-mediated liver LDL-C clearance [4]. The small intestine is the only organ responsible for the absorption of dietary and biliary cholesterol, leaving the unabsorbed cholesterol to be excreted in feces and together contributing to the body cholesterol homeostasis [13], [21], [33], [34]. Following intraluminal hydrolysis, free cholesterol is first incorporated into micelles and then transported across the ‘unstirred’ water layer to the brush border membrane of small intestine. This process has been demonstrated to be essential for the intestinal cholesterol absorption [15]. Thus, cholesterol micellarization assays have been developed and used, together with other methods, to study cholesterol absorption [35], particularly a product or compound that potentially disrupts cholesterol solubilisation in micelles [27]. It is well documented that plant stanols/sterols inhibit cholesterol absorption by interfering with cholesterol incorporation into micelles [13], [35], [36]. Therefore, in the present study we used plant stanols as a positive control to validate the cholesterol micellarization assay, which was further used to assess the effect of BBR. It was found that in the presence of BBR, the content of cholesterol in micelles was significantly decreased. This effect could be explained by the physical–chemical properties of BBR molecule. With both hydrophobic and hydrophilic binding sites, BBR can interact with the corresponding molecules of micelles. The bindings of BBR to hydrophobic and hydrophilic molecules of micelles lead to the formation of agglomerates and subsequently reduce the capacity of micelles to incorporate cholesterol [37], [38]. This property has in return been used in recent years to improve the bioavailability of BBR in mice and rats by mixing BBR in different emulsions or other similar solutions [39], [40]. Micellar size may affect the diffusion rate of micelles through the unstirred water layer and thus cholesterol absorption [41]. This potential effect was not measured in the present study.