Effects of gender, and SLCO1B1 and CYP7A1 polymorphisms on plasma bile acids in humans and the pharmacokinetics of therapeutic ursodeoxycholic acid

Bile acids are important steroid-derived molecules essential for fat absorption in the small intestine. They are produced in the liver and secreted into the bile. Bile acids are transported by bile flow to the small intestine, where they aid the digestion of lipids. Most bile acids are reabsorbed in the small intestine and return to the liver through the portal vein. The whole recycling process is referred to as the enterohepatic circulation, during which only a small amount of bile acids are removed from the body via faeces. The enterohepatic circulation of bile acids involves the delicate coordination of a number of bile acid transporters expressed in the liver and the small intestine. Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family, member 1B1 (SLCO1B1) gene, mediates the sodium independent hepatocellular uptake of bile acids. Two common SNPs in the SLCO1B1 gene are well known to affect the transport activity of OATP1B1. Moreover, bile acid synthesis is an important elimination route for cholesterol. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production. The aim of this thesis was to investigate the effects of SLCO1B1 polymorphism on the fasting plasma levels of individual endogenous bile acids and a bile acid synthesis marker, and the pharmacokinetics of exogenously administered ursodeoxycholic acid (UDCA). Furthermore, the effects of CYP7A1 genetic polymorphism and gender on the fasting plasma concentrations of individual endogenous bile acids and the bile acid synthesis marker were evaluated. Firstly, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of bile acids was developed (Study I). A retrospective study examined the effects of SLCO1B1 genetic polymorphism on the fasting plasma concentrations of individual bile acids and a bile acid synthesis marker in 65 healthy subjects (Study II). In another retrospective study with 143 healthy individuals, the effects of CYP7A1 genetic polymorphism and gender as well as SLCO1B1 polymorphism on the fasting plasma levels of individual bile acids and the bile acid synthesis marker were investigated (Study III). The effects of SLCO1B1 polymorphism on the pharmacokinetics of exogenously administered UDCA were evaluated in a prospective genotype panel study including 27 healthy volunteers (Study IV). A robust, sensitive and simple HPLC-MS/MS method was developed for the simultaneous determination of 16 individual bile acids in human plasma. The method validation parameters for all the analytes met the requirements of the FDA (Food and Drug Administration) bioanalytical guidelines. This HPLC-MS/MS method was applied in Studies II-IV. In Study II, the fasting plasma concentrations of several bile acids and the bile acid synthesis marker seemed to be affected by SLCO1B1 genetic polymorphism, but these findings were not replicated in Study III with a larger sample size. Moreover, SLCO1B1 polymorphism had no effect on the pharmacokinetic parameters of exogenously administered UDCA. Furthermore, no consistent association was observed between CYP7A1 genetic polymorphism and the fasting plasma concentrations of individual bile acids or the bile acid synthesis marker. In contrast, gender had a major effect on the fasting plasma concentrations of several bile acids and also total bile acids. In conclusion, gender, but not SLCO1B1 or CYP7A1 polymorphisms, has a major effect on the fasting plasma concentrations of individual bile acids. Moreover, the common genetic polymorphism of CYP7A1 is unlikely to influence the activity of CYP7A1 under normal physiological conditions. OATP1B1 does not play an important role in the in vivo disposition of exogenously administered UDCA.

Modeling the solubilities of fatty acids in supercritical carbon dioxide

A thermodynamic model was developed for modeling the solubilities of fatty acids in supercritical carbon dioxide. The model combines the Peng-Robinson equation of state (EOS) with the two parameter van der Waal's mixing rules. The model is applied to predict the solubilities of various fatty acids. The two adjustable interaction parameters in the model are found to vary linearly with the chain length of the fatty acids. Thus this model can be used to predict the solubilities of various fatty acids in supercritical carbon dioxide. (C) 2003 Elsevier Science B.V. All rights reserved.

Effect of dietary supplementation of tocoferol acetate alone and with varying combinations on growth, survival and fatty acids profile of Macrobrachium rosenbergii larvae through Moina micrura enrichment

A study was carried out to determine the effect of tocopherol acetate along with cod liver oil astaxanthin enriched Moina micrura (MC- control, Ml- tocopherol acetate enriched, M2-tocopherol acetate combined with cod liver oil (CLO) enriched and M3- tocopherol acetate combined with astaxanthin enriched) on growth, survival and fatty acid composition of M. rosenbergii (de Man) larvae (TC- unenriched Moina fed larvae, Tl- tocopherol acetate enriched Moina fed larvae, T2- tocopherol acetate + CLO enriched Moina fed larvae to T3 – tocopherol acetate+ astaxanthin enriched Moina fed larvae). Growth was expressed as the time taken in to the settlement of 95% post larvae. Maximum growth i.e., the lowest time taken to the 95% PL settlement (40 days) and the maximum survival percentage (61%) was observed in both T2 and T3 treatments fed with M2 and M3 Moina respectively. Minimum growth and survival was observed in unenriched Moina fed larvae (TC). In larval treatments T2, (larvae fed with (M2) vitamin E + CLO enriched Moina), showed a higher percentage of EPA, DHA and higher HUFA level than other treatments.

The triglyceride fatty acids from heart lipids of Puntius sarana and their variation with different sizes

The triglyceride fatty acid components from the heart lipid of Puntius sarana of different sizes have been characterized by thin-layer and gas liquid chromatography. Csub(10) to Csub(24) acids including both odd-numbered and branched chain acids were detected. The major constituents were ante-iso Csub(10), Csub(10), Csub(12:2), Csub(14), Csub(16), Csub(16:1),Csub(17), Csub(18) , Csub(18:1), Csub(18:2), Csub(18:3) and Csub(20:4) while twenty other acids were detected in lower proportion. The composition of these acids and their variation with size of fish have been investigated and discussed.

Selective release of fatty acids during lipid hydrolysis in frozen-stored milk fish (Chanos chanos)

Lipid hydrolysis and the nature of fatty acids lost as a result of lipid hydrolysis in milk fish (Chanos chanos) during frozen storage at -20°C is discussed in this paper. There was a preferential loss of saturated acids during the first three weeks of storage. This was followed by loss of polyunsaturated acids during the next seven weeks. Sharp decrease in the levels of monounsaturated acids was observed from the 10th week of frozen storage. These observations are due to the preferential hydrolysis of phospholipids with relatively high proportion of saturated acids during the first three weeks, followed by the hydrolysis of phospholipids with high proportions of polyunsaturated fatty acids from the 3rd to the 10th week, and finally, predominant hydrolysis of neutral lipids from the 10th week onwards. Storage of fish in the ice prior to freezing was found to accelerate lipid hydrolysis, especially that of neutral lipids, during frozen storage.

The effect of Rosmarinus officinalis and Zataria multiflora extracts on the stability of poly unsaturated fatty acids in frozen silver carp minced

The purpose of this study, Evaluation the effect of Rosmarinus officinalis and Thymus vulgaris extracts on the stability of poly unsaturated fatty acids in frozen Silver carp minced. Treatments include: Treatment 1 - Control: frozen meat packaged in conventional Treatment 2: Frozen Silver carp minced+Thyme 300 mg/kg in normal packaging Treatment 3: Frozen Silver carp minced+Rosemary 200 mg/kg in normal packaging Treatment 4: Frozen Silver carp minced+Rosemary compound (100 mg/kg) and Thyme (100 mg/kg) in normal packaging After rapid freezing of samples in the spiral freezer by individual quick freezing method, to maintain the cold temperature (-18) °C were transferred. Sampling and measurements to determine the fatty acid profile of the zero phase beginning in the first month and then every ten days, and 15 days in the second month of the third month after the monthly test. Identifying, defining and measuring the fatty acid profile by gas chromatography was performed. In this study, levels of both saturated and unsaturated fatty acids in three experimental and one control were identified as follows: A: saturated fatty acids: Meristic C14: 0/Palmitic C16: 0/Hepta decaenoic C17: 0/Stearic C18: 0/Arashidic C20: 0/B:Mono unsaturated fatty acids: palmitoleic C16: 1-W7/Oleic C18: 1-W9/Gadoleic C20: 1-W9 C:Poly unsaturated fatty acids: Linoleic C18: 2-W6/α-Linolenic C18: 3-W3 D:High unsaturated fatty acids: Arachidonic C20: 4-W6 Eicosapentaenoic acid C20: 5-EPA/W3 Docosahexaenoic C22: 6-DHA/W3 Results of this study was to determine, Thyme and rosemary extracts containing silver carp minced stored in freezing conditions, Stability of different types of fatty acids, monounsaturated fatty acids, poly-unsaturated fatty acids, omega-3 and omega-6 fatty acids are. So that none of the fatty acids measured were not significant 100% increase or decrease, While changes in the fatty acid oxidation during storage time is minimized. The results obtained from the fatty acid profiles and indicators of their and statistical tests show that treatment with rosemary extract More stable during storage (-18) ° C In comparison with the control and other treatments are shown; And at relatively low compared to other treatments and control samples oleic acid and linoleic acid, palmitic more. According to studies,in Silver carp minced that containing rosemary extract, end of the storage period of six months. Were usable, so even rosemary extract the shelf-life examples to increase more than six months.

Identification and determination of muscle's fatty acids and amino acids in Cobia and Indian squid

The present study aims to find the effect of freezing Time on the quality of Cobia (Rastrelliger kanagurta) and Indian Squid in commercial scale during freezing and subsequent frozen storage (−18◦C). Total time for freezing was significantly different (P<0.05) between the Cobia and Indian squid samples. The difference in the freezing time could be attributed to the varied quality of the 2 samples. Upon freezing, the moisture content decreased in Indian Squide samples compared to Cobia freezer where protein content decreased in both the samples. Upon freezing and during frozen storage, lipid oxidation products (peroxide value, and free fatty acid value) and volatile bases (total volatile base nitrogen) showed an increasing trend in both the samples with values slightly higher in Indian squid samples compared to cobia frozen samples. The total plate counts showed a significantly (P<0.05) decreasing trend in both the samples. K value did not show any significant (P<0.05) difference between the samples whereas the histamine formation was significantly (P<0.05) increased in Indian squid frozen samples compared to cobia samples. The taste and overall acceptability was significantly different (P<0.05) in cobia samples compared to Indian squid frozen samples on 5th month. Both samples were in acceptable condition up to 5 month but the Cobia frozen samples quality was slightly better than the air blast frozen samples.

Chemical ecology fatty acids of mollusks dominant species in intertidal zone of Chabahar Bay

Chemical ecology is the science of study and analysis of natural chemical products in result of biochemical processes in organisms and their reactions to variations of ecological and environmental parameters. In marine chemical ecology the existence of natural products in aquatic organisms and their ecological roles in marine animals and their reactions to environmental parameters variations will be studied. Among them, fatty acids are the most various and abundant ones in natural products which had been extracted from many marine organisms such as mollusks and algae. In this study selected animals were the dominant species of mollusks in intertidal zone of chabahar bay including gastropods, bivalves and polyplacophora classes. Nerita textilis and Turbo coronatus species are among gastropoda, Saccostrea cucullata is from bivalve, and Chiton lamyi is from polyplacophora. After seasonal sampling, separation and identification of natural products of these species, fatty acids had been isolated and identified by GC mass chromatography and their seasonal variations had been identified. In addition environmental factors of the location including pH, salinity temperature, dissolved oxygen, chlorophyll a and nutrients were measured monthly. Then the effect of seasonal variations of environmental factors on fatty acids had been studied by applying statistical analysis. GC/MS resulted thirteen fatty acids, which the most importants were myristic, stearic, oleic, palmitoleic, arachidonic and eicosapentaenoic acids. In majority of species palmitic acid was most abundant than the others and saturatedes had the most percentage levels than unsaturated ones. Although seasonal variations of identified fatty acids was not similar in species, but the majority of unsaturated ones had their maximum during winter, while saturated acids reached their maximum in summer. Statistical Analysis showed the strong correlations between Environmental factors and some fatty acids and temperature, nitrate, silicate and pH had strong correlations in all species. The species was studied from the point of lipid content and the results showed a good quality of lipid content in the selected species in the intertidal zone of Chabahar bay.

Influence of cold storage time on the protein changes and fatty acids deterioration of (Rutilus frisi kutum) during frozen storage

The main aim of this research was to identify fatty acids composition of Caspian sea of White fish Rutilus frisi kutum tissue and their changes during one year cold storage (-18Ċ).The secondary aim was to determine the changes of moisture, ash, protein, fat, and to investigate the effects of storage time on peroxide, TBAi, FFA, and extractability of myofibrillar proteins of the fish tissue during one year cold storage (-18 Ċ). 10 samples of (Rutilus frisi kutum) were randomly collected from Anzali landings. The samples were frozen at -30 Ċ and kept in cold storage at -18Ċ for one year. According to time table, the samples were examined. The results showed that 27 fatty acids were identified. The unsaturated fatty acids (UFA) and saturated fatty acids (SFA) were 74/09 and 21/63 %, respectively, in fresh tissue. So that DHA (C22:6) oleic acid (C18:1c) had high amounts (15/07 ,20/57 ) among the UFA and palmitic acid (C16:0) was the most (13/09 %) among the SFA. The effects of freezing and cold storage on fish tissue showed that UFA and SFA contents have reached to 58/79 and 22/17 %, respectively, at the end of cold storage. It indicated that these compound change to each other during frozen storage. Also ω-3 and ω-6 series of fatty acids was 24/22 and 15/56% in fresh tissue, but their contents decreased to 8/68 and 5/11% at the end of period. Among the fatty acids C22:6, C18:1c and C16:0 had the most changes. The changes of fatty acids were significantly at 95% level expected for C18:0. Results showed that moisture, ash, protein, and fat contents were 75/9±0/03, 1/28±0/012, 21/8±0/2, and 4/1±0/01 % respectively, in fresh tissue. The moisture, ash, protein, and fat contents were 72/3±0/04, 1/83±0/05, 1/91±0/01 and 19/9±0/01 % respectively, at the end of storage period. Lipid damage was measured on the basis of free fatty acids (FFA), peroxide value (PV), and Thiobarbituric acid index (TBA-i). PV, TBARS and FFA concentration of frozen Caspian Sea white fish stored at -18 Ċ the temporal variation of these three variables were statistically significant (p<0.001). Results of White fish myofibrillar proteins showed aggregation of bound reduced for stored at 12 months. SDS-PAGE analysis revealed that, the intensity of the myosin heavy chain and actin bound was reduced with increasing storage time. SDS-PAGE patterns showed that myosin heavy chain was much more susceptible to hydrolysis than actin. Key words: Rutilus frisi kutum, frozen storage, ω-3, ω-6, protein myofibrillar