Hypolipidemic and anti-atherogenic effects of long-term Cholestin (Monascus purpureus-fermented rice,red yeast rice) in cholesterol fed rabbits

Long-term effects of Cholestin (Monascus purpureus rice; red yeast rice) on serum lipids and severity of atherosclerosis were examined in rabbits fed for 200 days on a semi-purified diet containing 0.25% cholesterol. Serum total cholesterol was 25 and 40% lower, respectively, in rabbits fed 0.4 or 1.35 g/kg/day of Cholestin (Monascus purpureus rice; red yeast rice) compared to controls. This treatment also lowered serum LDL cholesterol. This 200-day treatment significantly reduced serum triglycerides and atherosclerotic index (ratio of non-HDL-cholesterol to HDL-cholesterol). Although similar reductions of total, LDL-cholesterol and triglycerides were observed, a parallel group of rabbits fed lovastatin (0.0024 g/kg/day) failed to reduce the index significantly. Apolipoprotein A(1) was increased and apolipoprotein B was reduced in all treatment groups. Severity of atherosclerosis was reduced significantly in all treatment groups. The sudanophilic area of involvement was 80.6% in controls, and reduced significantly; to 30.1% on the low dose of Cholestin (Monascus purpureus rice; red yeast rice), and 17.2% on the high dose. Lovastatin reduced severity of lesions by 89% (sudanophilia) and 84% (visual). Visual grading of lesion severity showed reduction by 38% and 68%.     

Effect of dietary fish on antioxidant parameters of normal and cholesterol stressed rats

Feeding fish (Sardinella longiceps) to normal rats increased lipid peroxidation and total and Se-dependent glutathione peroxidase (GSH-px) activity in erythrocytes and manganese dependent superoxide dismutase (Mn-SOD) activity in liver. Feeding fish to cholesterol stressed rats showed a significant increase in the activity of GSH-px and cholesterol feeding alone, resulted in a significant increase in the lipid peroxidation and liver Mn-SOD activity. The results suggest that the high polyunsaturated fatty acid content of S. longiceps, the fish abundantly available in the west coast of India, does not have any deleterious effect by way of free radical generation. The observed lipid peroxidation is not critical as is evident from the results of glutathione level and other scavenging enzymes.     

The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil

Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body.     

Effect of red mold rice supplements on serum and meat cholesterol levels of broilers chicken

Monacolin K is a secondary metabolite produced by Monascus species. It was found that it is able to decrease cholesterol levels. In this study, red mold rice (RMR) was added to the diet of Arbor Acres broiler chickens, and the cholesterol level in meat, as well as the concentration of triglyceride, the high-density lipoprotein cholesterol (HDL-C), and the low-density lipoprotein cholesterol (LDL-C) in the serum were evaluated. Four-week-old broilers are studied and divided into four groups in that each group contains 15 subjects. A 3-week experimental feeding trial was conducted in which three groups of broilers were fed 2.0, 5.0, and 8.0% of RMR (RMR groups) within their diet, respectively, and the result was compared to the control group. The results indicated that for each RMR group, the cholesterol content was significantly lower than that of the control group; in addition, their meat products contain higher level of unsaturated fatty acids. Triglyceride and cholesterol concentration in serum was also found to be considerably lower in RMR groups when compared to control group. Finally, in RMR groups, HDL-C/LDL-C and HDL-C/cholesterol ratios were all higher than those of the control group. In short, the results demonstrated that the cholesterol levels could be lowered by adding RMR to the diet of chickens.     

Effect of fish oil on offensive and defensive factors in gastric ulceration in rats

The effect of fish oil (FO) derived from Scomberoides commersonianus containing omega-3 polyunsaturated fatty acids was studied on gastric ulcers and as well as on offensive and defensive factors in gastric mucosal damage, following experimental gastric ulceration. FO significantly reduced the severity of ulceration in gastric ulcers induced by aspirin, cold-restraint stress (CRS), alcohol, and pylorus ligation. The results also indicated the potentiality of FO in maintaining the integrity of gastric mucosa by virtue of its effect on both offensive and defensive gastric mucosal factors. It decreased the offensive acid-pepsin secretion and augmented the defensive factors like mucin secretion, cellular mucus and life span of mucosal cells following pylorus ligation. FO significantly increased activity of anti-oxidant enzymes (catalase and glutathione peroxidase) and decreased lipid peroxidation in gastric mucosa of CRS rats. The study indicates the beneficial role of FO in gastric ulceration by inhibition of offensive mucosal factors and oxidative stress, and augmentation of defensive mucosal factors.     

原油和消油剂对鱼类毒性的研究进展

原油对鱼类的毒性主要来自其水溶性成分,可导致鱼卵死亡或发育畸形,并造成鱼类麻痹、发炎、粘膜受损和死亡。消油剂的使用在分散了油膜的同时也带来二次污染,其活性剂对鱼类产生新的毒性影响。消油剂将原油分散为乳化颗粒并能进入鱼体内,加大了原油的毒性并延长其作用时间。综述了原油和消油剂对鱼类毒性的研究进展,展望了鱼类在相关毒性试验领域的应用及发展方向。     

Effect of fish oil supplementation on plasma oxidant/antioxidant status in rats

The aim of this study was to investigate effect of dietary omega-3 fatty acid supplementation on the indices of in vivo lipid peroxidation and oxidant/antioxidant status of plasma in rats. The plasma thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels, and activities of xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were studied in male Wistar Albino rats after ingestion of 0.4 g/kg fish oil (rich in omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid) for 30 days and compared to untreated control rats. The rats in the treated group had significantly higher SOD activity (P < 0.001), NO levels (P < 0.01) and decreased TBARS levels (P < 0.05) with respect to controls whereas GSH-Px and XO activities were not significantly different between the groups. None of the measured parameters had significant correlation with each other in both groups. We conclude that dietary supplementation of omega-3 fatty acids may enhance resistance to free radical attack and reduce lipid peroxidation. These results support the notion that omega-3 fatty acids may be effective dietary supplements in the management of various diseases in which oxidant/antioxidant defence mechanisms are decelerated.     

Effect of fish oil on mitochondrial respiration in isoproterenol induced myocardial infarction in rats

Following isoproterenol treatment mitochondrial lipid peroxidation, phosphoslipase activity, lactate and calcium increased significantly, while activities of tricarboxylic acid cycle enzymes, enzymes of respiratory chain and ATP production showed decline. Oxidative phosphorylation was also affected on isoproterenol treatment with significant reduction in all the variables. Fish oil pretreatment in isoproterenol treated rats showed improved mitochondrial energy metabolism. The results suggest cardioprotective effect of fish oil.     

Dietary oxidized linoleic acid enhances liver cholesterol biosynthesis and secretion in rats

Based on studies showing that excretion of cholesterol is elevated in rats fed oxidized linoleic acid, we hypothesized that cholesterol metabolism is enhanced under such oxidative stress. Liver cholesterol biosynthesis and secretion and fecal cholesterol excretion were studied in rats fed for 4 weeks diets containing 10% oxidized linoleic acid. Incubation of liver slices with 1-(14)C acetate and intraperitoneal injection of 5-(3)H-mevalonate showed the occurrence of enhanced hepatic cholesterol biosynthesis and elevated liver cholesterol secretion in animals subjected to oxidative stress. In addition, impaired liver cholesterol uptake was suggested. Higher levels of excreted cholesterol observed in the experimental animals were accompanied by augmented levels of liver phospholipids, primarily phosphatidylcholine, which most likely increased to enable the excessive cholesterol excretion. This study thus demonstrates that ingestion of oxidized lipids causes profound alterations in cholesterol metabolism.     

Effect of oxidized cholesterol on age-associated changes to immune parameters in spleen lymphocytes and peritoneal exudate cells derived from rats

The effects of oxidized cholesterol on immune parameters were examined by using spleen lymphocytes and peritoneal exudate cells (PEC) derived from 5-week- (Young) and 9-month-old (Adult) rats. The immunoglobulin (Ig) G and IgM production was inhibited by oxidized cholesterol in the rats of both ages when lymphocytes were exposed to 30 micrograms/ml of oxidized cholesterol for 24 hr. The intracellular IgA level was also lowered by 30 micrograms/ml of oxidized cholesterol, irrespective of age. In contrast, IgE production was significantly increased by the addition of 30 micrograms/ml of oxidized cholesterol in only young lymphocytes. Moreover, oxidized cholesterol enhanced the intracellular histamine accumulation in only adult PEC, although the total histamine level produced by PEC was similar in the rats of both ages. These results thus suggest the possibility that oxidized cholesterol can have different effects on the age-related modulation of immune functions such as Igs production and histamine release.     

Effect of red pigment on amyloidization of yeast

Amyloid-bound thioflavin T fluorescence was studied in lysates of yeast strains that carry mutations in the ADE1 or ADE2 genes and accumulate red pigment as a result of the polymerization of aminoimidazole ribotide (an intermediate of adenine biosynthesis). The fluorescence is drastically enhanced in cells grown in media with high concentrations of adenine (100 mg/l), which suppresses the accumulation of red pigment. Mutations that block the first stages of purine biosynthesis de novo also impede the accumulation of red pigment and produce the same effect on thioflavin fluorescence. Mutations in ADE1 or ADE2 genes in originally white prototrophic strains considerably suppress fluorescence. The fraction of protein polymers was studied by agarose gel electrophoresis, which permitted us to conclude that reduced fluorescence intensity was associated with decreased amyloid content in cells that accumulate red pigment. Model experiments with insulin fibers demonstrate that red pigment binds fibrils and blocks their interaction with thioflavin T. A comparison of lysate pellet proteins from red and white isogenic strains separated by 2D electrophoresis followed by MALDI analysis allowed us to identify 23 pigment-dependent proteins. These proteins mostly belong to functional classes of chaperones and proteins involved in glucose metabolism, which closely correspond to the prion-dependent proteins that we characterized previously. We suppose that the binding of red pigment with amyloid fibrils prevents the generation of prion aggregates and impedes prion propagation by blocking fibril contact with chaperones.     

Effect of excessive intake of thermally oxidized sesame oil on lipids,lipid peroxidation and antioxidants' status in rats

Fresh and thermally oxidized sesame, groundnut and coconut oils were fed to different groups of rats, as high fat diet (20%). Feeding fresh and thermally oxidized oils increased the levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), and phospholipids but high density lipoprotein cholesterol (HDL-C) decreased in all the experimental animals. The levels of very low density lipoproteincholesterol (VLDL-C) and triacylglycerol increased only in groundnut and coconut oils-fed groups and decreased in sesame oil-fed group when compared with the control. When fresh and the corresponding thermally oxidized oils-fed groups were compared with the control, total cholesterol and LDL-cholesterol alone increased while triacylglycerol, VLDL-cholesterol, HDL-cholesterol, HDL/LDL ratio and phospholipids decreased. Thiobarbituric acid reacting substances increased in all the experimental animals and more so in corresponding thermally oxidized oils. It was less pronounced in sesame oil-fed groups when compared with the corresponding other oils-fed groups. Feeding of thermally oxidized oils decreased the levels of vitamin E, vitamin C and reduced glutathione when compared with fresh oils. Among the three thermally oxidized edible oils, sesame oil exhibited lesser risk for hyperlipidemic disorders.     

Intestinal absorption of fish oil in rats previously adapted to diets containing fish oil or corn oil.

A study was conducted to evaluate whether the composition of previous dietary fat affects the absorption and composition of lymph obtained after a meal of fish oil. Adult male Sprague-Dawley rats were fed diets containing either corn oil or fish oil (MaxEPA) for 2 weeks. They were then given intraduodenally a bolus of an emulsion of 0.5 ml of fish oil plus 0.5 ml of 20 mM sodium taurocholate. Intestinal lymph was collected from a cannula in the main intestinal lymph trunk for various times after oil administration. Rats proportion of the test dose fo fish oil than those fed corn oil. There was an effect of previous diet on the fatty acid composition of the lymph. Rats fed fish oil had a higher percentage of eicosapentaenoic and docosahexaenoic acids in the lymph lipids than those fed corn oil while those fed corn oil had a higher percentage of linoleic acid. These results rule out decreased intestinal absorption as a mechanism for the hypotriacylglycerolemic effect of dietary fish oils. They also indicate a significant contribution of endogenous lipids to the fatty acids in lymph.     

Effect of long term feeding of rice bran oil upon lipids and lipoproteins in rats

The effects of feeding two levels of rice bran oil (RBO) on the growth, lipid parameters, and fatty acid composition of the plasma and liver of rats (Wistar strain) were compared with those produced on animals which had been fed the same levels of peanut oil (PNO). The control animals were fed synthetic diets containing 5 and 20% peanut oil (PNO) and the experimental groups were fed similar diets, containing the same level of rice bran oil (RBO). There was no significant difference with respect to the organ weights between the control and the experimental groups. In general, groups fed 20% oil gained more weight than groups fed 5% oil. The animals which received rice bran oil in their diet had, in general, comparatively lower levels of cholesterol, triglycerides and phospholipids. On the other hand, animals receiving 20% rice bran oil in their diet, showed an increase of 20% in high density lipoproteins (HDL-C), within 18 weeks (p<0.05), when compared to the animals fed with peanut oil. Similarly, low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were lower in RBO-fed groups, than in the PNO-fed groups. There was, however, no significant differences in the cholesterol/phospholipid (C/P) ratio of the two groups. Analysis of plasma and of liver fatty acids indicated, in a general way, the type of fat consumed. There were no significant difference in the P/S ratio, nor any in the oleic/linoleic, oleic/stearic, palmitoleic/palmitic, oleic/palmitic, and oleic/palmitoleic ratios. Furthermore, levels of saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were identical in both the groups. Thus, our results suggest that feeding a high level of rice bran oil (RBO) has no deleterious effect on the growth and blood lipid profile of rats.Abbreviations PNO peanut oil - RBO rice bran oil - HDL-C high density lipoprotein cholesterol - LDL-C low density lipoprotein cholesterol - VLDL-C very low density lipoprotein cholesterol - SAFA saturated fatty acids - MUFA mono-unsaturated fatty acids     

Effects of salmon oil and corn oil on plasma lipid level and hepato-biliary cholesterol metabolism in rats

The aim of this work was to compare the effects of n-3 and n-6 fatty acids on plasma lipid level and hepato-biliary cholesterol metabolism by studying rats fed semi-synthetic diets enriched with either 10% salmon oil, 10% corn oil, or a blend of 6% corn oil and 4% salmon oil. After 4 weeks of feeding, a drop in plasma lipid level was noted in the salmon oil group in comparison to the control group, whereas no change was observed in the corn oil group. An increase in production of cholesterol ester by the liver was recorded in the salmon oil group with a marked enhancement in acyl-CoA:cholesterol acyltransferase (ACAT: EC 2.3.1.26) activity and hepatic cholesterol concentration. Corn oil did not affect either ACAT activity or hepatic cholesterol storage. All bile parameters (flow, bile salts, phospholipids, cholesterol) increased in the salmon oil group, but the molar ratio of cholesterol participation in the bile secretion decreased. These changes in bile composition, as well as in hepatic metabolism of cholesterol, may help to explain the hypolipidemia following the intake of fish oil.     

Dietary oxidized cholesterol decreases expression of hepatic microsomal triglyceride transfer protein in rats

The aim of this study was to compare the effects of dietary oxidized cholesterol and pure cholesterol on plasma and very low density lipoprotein (VLDL) lipids and on some parameters of VLDL assembly and secretion in rats fed two different dietary fats. Four groups of male growing Sprague-Dawley rats were fed diets containing pure or oxidized cholesterol (5 g/kg diet) with either coconut oil or salmon oil as dietary fat (100 g/kg diet) for 35 days. Rats fed oxidized cholesterol supplemented diets had significantly lower concentrations of triglycerides and cholesterol in plasma and VLDL than rats fed pure cholesterol supplemented diets irrespective of the type of fat. In addition, rats fed oxidized cholesterol supplemented diets had significantly lower relative concentrations of microsomal triglyceride transfer protein messenger ribonucleic acid (mRNA) than rats fed pure cholesterol supplemented diets. In contrast, hepatic lipid concentrations and the relative concentration of apolipoprotein B mRNA were not influenced by the dietary factors investigated. Parameters of hepatic lipogenesis (relative mRNA concentration of sterol regulatory element binding protein-1c and activity of glucose-6-phosphat dehydrogenase) were significantly reduced by feeding fish oil compared to coconut oil, but were not affected by the type of cholesterol. In conclusion, the data of this study suggest, that dietary oxidized cholesterol affects VLDL assembly and/or secretion by reducing the synthesis of MTP but not by impairing hepatic lipogenesis or synthesis of apolipoprotein B.