Influence of dietary hexachlorocyclohexane isomers on lipid metabolism in albino rats

Dietary intake of beta- and gamma-hexachlorocyclohexane (beta- and gamma-HCH) by albino rats for two weeks (at 800 ppm level) resulted in impairment of lipid metabolism, viz. hyperlipemia and fatty metamorphosis of liver. Liver fat content was increased by both beta- and gamma-HCH. Significant increases were observed in triglyceride and phospholipid fractions of blood in these experimental animals. The incorporation of [14C]acetate and palmitate into liver and blood lipids was higher in HCH pretreated animals, suggesting a higher rate of fat synthesis in liver and of secretion as well.     

Influence of dietary capsaicin and onion on the metabolic abnormalities associated with streptozotocin induced diabetes mellitus

Effect of feeding 15 mg% capsaicin diet or 3% freeze dried onion powder containing diet were examined in albino rats rendered diabetic with streptozotocin injection. Diabetic rats maintained on onion diet for 8 weeks excreted comparatively less amounts of albumin, urea, creatinine and inorganic phosphorus. Dietary onion also partially reversed the abnormalities in plasma albumin, urea, creatinine and inorganic phosphorus in diabetic animals. Onion also produced a significant reduction in hyperglycemic status of diabetic animals. Diabetic rats maintained on onion diet had a lowered relative liver weight at the end of the study compared to diabetic control group. Diabetic rats fed onion diet also exhibited lowered lipid peroxides in circulation and in urine when compared to diabetic control group. Blood cholesterol was lowered significantly by dietary onion in diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood phospholipids and tr iglycerides also brought about by dietary onion. Hepatic cholesterol, triglycerides, phospholipids which were elevated under diabetic condition were countered significantly by dietary onion. Dietary capsaicin did not have any significant influence on any of the parameters tested in diabetic rats. Thus, the study reveals that onion feeding improves the metabolic status in diabetic condition, probably because of its hypoglycemic as well as hypocholesterolemic effect. (Mol Cell Biochem 175: 49–57, 1997)     

Fate of Mycobacterium tuberculosis inside rate peritoneal macrophages in vitro

Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing diet for 8 weeks. Blood cholesterol was lowered significantly by dietary curcumin in these diabetic animals. Cholesterol decrease was exclusively from LDL-VLDL fraction. Significant decrease in blood triglyceride and phospholipids was also brought about by dietary curcumin in diabetic rats. In a parallel study, wherein diabetic animals were maintained on a high cholesterol diet, the extents of hypercholesterolemia and phospholipidemia were still higher compared to those maintained on control diet. Curcumin exhibited lowering of cholesterol and phospholipid in these animals also. Liver cholesterol, triglyceride and phospholipid contents were elevated under diabetic conditions. Dietary curcumin showed a distinct tendency to counter these changes in lipid fractions of liver. This effect of curcumin was also seen in diabetic animals maintained on high cholesterol diet. Dietary curcumin also showed significant countering of renal cholesterol and triglycerides elevated in diabetic rats.In order to understand the mechanism of hypocholesterolemic action of dietary curcumin, activities of hepatic cholesterol-7a-hydroxylase and HMG CoA reductase were measured. Hepatic cholesterol-7a-hydroxylase activity was markedly higher in curcumin fed diabetic animals suggesting a higher rate of cholesterol catabolism. (Mol Cell Biochem 166: 169-175, 1997)     

Biochemical toxicity of hexachlorocyclohexane and its gamma-isomer in albino mice

Dietary hexachlorocyclohexane (HCH) and gamma-isomer of HCH produced significant increase in liver weights of mice. Elevated levels of alanine and aspartate aminotransferases and of alkaline phosphatase in the blood of these animals suggested hepatotoxicity. Hepatic soluble enzymes--aspartate aminotransferase and lactate dehydrogenase--were markedly lowered. Among the hepatic lysosomal enzymes, acid phosphatase and acid cathepsin were increased in the experimental animals. Hepatic glucose-6-phosphatase was lowered by HCH while aldolase activity was increased. Hydrolytic enzymes in small intestine, viz., disaccharidases, lipase, amylase, dipeptidase and phosphatases, were also affected by dietary HCH and gamma-HCH. The results suggested cellular toxicity in hepatocytes of HCH and gamma-HCH fed animals, and also interference in gastrointestinal absorption.     

The influence of dietary selenium and vitamin E on glutathione peroxidase and glutathione in the rat

The effect of dietary selenium (Se) and vitamin E supplementation on tissue reduced glutathione (GSH) and glutathione peroxidase activity has been studied in the rat. Increasing Se intake by 0.4 ppm gave significantly higher enzyme levels in all tissues studied, an effect not influenced by vitamin E intake. Further increasing Se to 4 ppm gave higher enzyme levels in red blood cells only, while in liver was there was a significant decrease in enzyme activity probably reflecting Se hepatotoxicity. In the absence of Se supplements increasing dietary vitamin E to 100 mg/kg diet significantly increased enzyme activity but this effect was modified by simultaneous Se supplementation.Se intake had no effect on GSH levels. Rats on high vitamin E intake 500 mg/kg had a significantly higher tissue GSH level. Dietary Se had a sparing effect on vitamin E, rats supplemented with Se having significantly raised plasma vitamin E levels.These results confirm the role of selenium in glutathione peroxidase and also show that vitamin E influences the activity of the enzyme.     

The effect of dietary menhaden,olive, and coconut oil fed with three levels of vitamin E on plasma and liver lipids and plasma fatty acid composition in rats

The effect of dietary fats with varying degrees of unsaturation in the presence of different concentrations of vitamin E on tissue lipid levels was studied in rats. Rats were fed either menhaden oil, olive oil or coconut oil at 15% levels with either 0.1, 0.3 or 0.6 mg/g of vitamin E as alpha-tocopherol for four weeks. Rat serum and liver were analyzed for total cholesterol, HDL-cholesterol, triacylglycerol and phospholipids. In addition, fatty acid composition of serum lipids was also analyzed. Serum total cholesterol and triacylglycerol were significantly lower in rats fed menhaden oil than in those fed olive or coconut oil, while the HDL-cholesterol was significantly higher in serum of rats fed menhaden and olive oil than in those fed coconut oil. Levels of vitamin E in the diet had only a significant effect on serum cholesterol and liver phospholipids. The Pearson correlation coefficient showed a significant positive relationship between serum triacylglycerol and total cholesterol, and a negative correlation between triacylglycerol and HDL-cholesterol, and between total and HDL-cholesterol.In the liver, total cholesterol was significantly higher in rats fed coconut oil than in rats fed menhaden oil. Total liver phospholipids were lower in rats fed either coconut oil or olive oil compared to those fed menhaden oil, especially with higher levels of vitamin E intake. Higher levels of vitamin E in the diet appear to increase triacylglycerol and phospholipids in livers of rats fed menhaden oil. In the liver a significant negative correlation was observed between phospholipids and cholesterol. The type and degree of unsaturation (polyunsaturated fatty acids in menhaden oil, monounsaturated fatty acids in olive oil and saturated fatty acids in coconut oil) significantly affected plasma and tissue lipids.     

The effect of variable magnesium intake on potential factors influencing endurance capacity

Rats fed a magnesium (MG) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 μg/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.     

Effects of dietary protein type on the response of lipid metabolism to orotic acid in rats

The effects of orotic acid supplementation to casein, egg protein, soy protein and wheat gluten diets on the lipids of liver and serum were compared. When orotic acid was added, the contents of total lipids and triacylglycerol in the liver of the casein group were significantly higher or tended to be higher than those of the other three dietary groups. Dietary orotic acid had no effect on the food intake. The liver weight, and liver total lipids, triacylglycerol, cholesterol and phospholipids were increased or tended to be increased by the addition of orotic acid. The serum triacylglycerol level was decreased by the addition of orotic acid to either the casein or soy protein diet. Thus, the response to liver lipid accumulation induced by orotic acid feeding depended on the dietary protein type.     

Effects of Dietary Polychlorinated Biphenyls and Protein Level on Liver and Serum Lipid Metabolism of Rats

The effects of polychlorinated biphenyls (PCB) and dietary protein level on the liver and serum lipid metabolism of rats were studied. Rats were fed an experimental diet containing 7 or 30% casein with or without 0.1 % PCB for 24 days. Dietary PCB increased the level of triglyceride, phospholipid and cholesterol in the liver. The accumulation of triglyceride and cholesterol in liver was markedly increased with a low protein diet. The incorporation of injected ³H₂O into liver cholesterol was increased by PCB, but not affected by the dietary level of protein. The incorporation of the tracer into liver fatty acids was not increased by PCB intake. Dietary PCB also raised serum cholesterol and phospholipid, while PCB decreased triglyceride level, especially in rats on low protein diet. In addition, PCB intake clearly raised serum high density lipoprotein and diminished very low density lipoprotein. In the low protein group, PCB markedly repressed the incorporation of ³H₂O into serum lipids. The results suggest that the hepatic lipids accumulation by the addition of 0.1 % PCB to a low protein diet might be mainly ascribed to a repression in the transport of triglyceride from liver to blood. KEY WORDS: PCB, dietary protein, liver lipids, serum lipoprotein.     

Effects of Dietary PCB and Caffeine on Serum and Liver Lipids and Urinary Ascorbic Acid in Rats after Different Times

Comparison of the effects of dietary PCB (0.03%) and caffeine (0.3%) on serum and liver lipids, and urinary ascorbic acid was done after different times. Serum total cholesterol, liver total lipids and triglyceride (TG) were found to continuously increase at 2, 4, and 8 weeks, but urinary ascorbic acid, serum TG and liver phospholipids were elevated up to 4 weeks in the PCB-fed rats. Liver cholesterol showed a decreasing trend after 2 weeks. On the other hand, dietary caffeine continuously increased serum cholesterol up to 8 weeks. Urinary ascorbic acid remained the same throughout the experimental period, but was significantly higher than in the respective controls at all times. Serum TG also remained the same, but was lower than in the respective controls. Liver total lipids, cholesterol and TG did not change in the caffeine-fed animals. The results clearly indicate that dietary PCB increased all the parameters investigated whereas caffeine elevated serum cholesterol and urinary ascorbic acid, but depressed the serum TG concentration.     

Nutrient and drug effects on cholesterol metabolism in the laying hen

The laying hen is a highly dynamic model for studies of cholesterol metabolism. Cholesterol biosynthesis takes place primarily in the liver where it is regulated by both diet and drugs. Ovarian cholesterol biosynthesis follows a pattern different from that in liver and is not influenced by dietary fat or cholesterol. The hen responds to high levels of dietary polyunsaturated fat by increasing cholesterol biosynthesis, egg cholesterol deposition, and fecal bile acid excretion. Dietary cholesterol curtails liver cholesterol biosynthesis and may or may not result in increased egg cholesterol deposition and/or increased fecal steroid excretion depending on the level of cholesterol intake. Dietary plant sterols and fiber may moderate egg cholesterol deposition but the conditions under which this takes place are not well defined. D-Thyroxin reduces blood cholesterol, increases blood sterol turnover, and increases egg cholesterol concentration. Triparanol and azasterols prevent desmosterol conversion to cholesterol with resultant appearance of both sterols in blood and eggs. Probucol moderates egg cholesterol deposition by reducing synthesis and/or transfer of the sterol to the egg. Implications for the use of the hen in cholesterol metabolism studies are discussed.     

Gestational changes in concentrations of selenium and zinc in the porcine fetus and the effects of maternal intake of selenium

The effect of maternal dietary selenium (Se) and gestation on the concentrations of Se and zinc (Zn) in the porcine fetus were determined. Mature gilts were randomly assigned to treatments of either adequate (0.39 ppm Se) or low (0.05 ppm Se) dietary Se. Gilts were bred and fetuses were collected throughout gestation. Concentrations of Se in maternal whole blood and liver decreased during gestation in sows fed the low-Se diet compared to sows fed the Se-supplemented diet. Maternal intake of Se did not affect the concentration of Se in the whole fetus; however, the concentration of Se in fetal liver was decreased in fetuses of sows fed the low-Se diet. Although fetal liver Se decreased in both treatments as gestation progressed, the decrease was greater in liver of fetuses from sows fed the low-Se diet. Dietary Se did not affect concentrations of Zn in maternal whole blood or liver or in the whole fetus and fetal liver. The concentration of Se in fetal liver was lower but the concentration of Zn was greater than in maternal liver when sows were fed the adequate Se diet. These results indicate that maternal intake of Se affects fetal liver Se and newborn piglets have lower liver Se concentrations compared to their dams, regardless of the Se intake of sows during gestation. Thus, the piglet is more susceptible Se deficiency than the sow.     

Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats

To investigate the manganese status in magnesium deficiency, 40 male Wistar rats, 3 wk old, were divided into two groups and fed a magnesium deficient diet or a normal synthetic diet for 2 wk. Dietary magnesium depletion decreased magnesium levels in brain, spinal cord, lung, spleen, kidney, testis, bone, blood, and plasma, while it elevated the magnesium level in liver. In magnesium-depleted rats, calcium concentration was increased in lung, liver, spleen, kidney, and testis, while it was decreased in tibia. In magnesium-depleted rats, manganese concentration was decreased in plasma and all tissues except adrenal glands and blood. Dietary magnesium depletion diminished pyruvate carboxylase (EC 6.4.1.1) activity in the crude mitochondrial fraction of liver. Positive correlation was found between the liver manganese concentration and the pyruvate carboxylase activity. In the magnesium-depleted rats, glucose was decreased while plasma lipids (triglycerides, phospholipids, and total cholesterol) were increased. These results suggest that dietary magnesium deficiency changes manganese metabolism in rats.     

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.     

Age-related changes of dietary intake and blood eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels in Japanese men and women

We studied the relationship between dietary intake and the blood compositions of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (ARA) in four study groups with different ages and sexes. One hundred and four subjects were recruited. Dietary records together with photographic records from 28 consecutive days were amassed and the fatty acid composition in erythrocyte membranes and plasma lipid fractions was analyzed. Fish intake in the elderly group was significantly higher than that in the young group in both men and women. The compositions of ARA in erythrocytes and plasma phospholipids in the elderly were lower than those in the young, but the ARA intake was nearly identical. In the elderly group, the percentage of dietary ARA consumed at the same time as EPA and DHA derived from fish was high. We considered that these fatty acids markedly inhibited the incorporation of dietary ARA into blood phospholipids.     

Effects of Dietary Oxidized Cholesterol on Lipid Metabolism in Differently Aged Rats

Male Sprague-Dawley rats, 4 weeks (young) or 8 months (adult) of age, were fed one of three purified diets free of or containing either 0.5% cholesterol or 0.5% oxidized cholesterol (92% oxidized cholesterol) for 3 weeks. Feeding of oxidized cholesterol caused a significant reduction of food intake, body weight gain, and relative liver weight in rats of both ages. The activity of the HMG-CoA reductase and cholesterol 7α-hydroxylase of liver microsomes, the key enzymes in cholesterol synthesis and catabolism, respectively, was lowered by oxidized cholesterol compared to the diet free of cholesterol in both ages, and the difference was significantly in the adult. On the other hand, the activity of Δ6-desaturase of liver microsomes, a key enzyme in linoleic acid metabolism to arachidonic acid, was significantly increased by oxidized cholesterol in adult rats, leading to the increase in linoleic acid desaturation index [(20:3n-6 + 20:4n-6)/18:2n-6] in liver phospholipids. Oxidized cholesterol reduced the concentration of cholesterol in serum and liver. Also, the fecal excretion of acidic steroids was lower in rats fed the oxidized cholesterol diet than in those fed the cholesterol-free diet. Thus, oxidized cholesterol significantly influenced cholesterol and fatty acid metabolism in particular in adult rats.     

Influence of fast, body weight and diet on serum cholesterol, triglycerides, and phospholipids concentrations in the aging rat

The present study was performed to document factors playing a role in the age-related increase of serum total cholesterol, triglycerides, and phospholipids in male WISTAR rats. In 59 and 122 week old rats, serum concentrations of all three parameters were significantly higher than those determined in younger rats (15-17 weeks of age). Serum triglycerides and cholesterol concentrations were higher in post absorptive than in fasting state. In mature rats of same age (59 weeks), mean concentrations of cholesterol, triglycerides, and phospholipids were significantly higher in the heavier animals than in the others. A strong correlation could be established between body weight and serum cholesterol or triglycerides of these animals. The composition of diet appears to play a role in serum cholesterol concentration but not in serum triglycerides concentration in old rats (59-65 weeks of age). This effect is demonstrated even if daily caloric intake and daily body weight gain of old rats (40-50 weeks of age) were not significantly different with both diets tested (2900 and 3250 cal/kg). In conclusion old Wistar rats develop increased concentrations of serum lipids parameters.     

Oral toxicity of Madhuca butyracea Macb. saponins to albino rats

Saponins, isolated from M. butyracea, were assessed for their acute and subacute oral toxicity in albino rats. Acute doses of saponins caused mortalities and LD50 and LD90 values were 330 and 430 mg/kg body wt respectively. Severe diarrhoea, restlessness and histopathological changes were observed in liver and kidney. Diets containing saponins at 0,250,500 and 1000 ppm for 14 weeks did not affect food intake, growth or organ weights, but induced mild histological changes in liver and kidney and altered the serum levels of alkaline phosphatase, blood urea nitrogen, cholesterol and proteins, particularly in female rats.     

Effects of dexamethasone on lipid metabolism in rat organs

Injecting of dexamethasone (10 mg/kg body weight) for 8 days to rats decreased the body weight and feed intake by 29 and 50%, respectively. The increase in weights of liver, heart, kidneys and testes per 100 g body weight was 55, 37, 33 and 13%, respectively. Though, in general, the triglyceride content increased in all the organs, maximum increase (9-fold) was observed in the liver. The plasma showed elevated levels of triglycerides, cholesterol and phospholipids. In hepatic mitochondrial membranes, the content of protein, phospholipids and cholesterol decreased/g tissue. The percent 14C distribution, as a part of total incorporation in nonpolar lipids, of [14C]acetate into triglycerides of liver, kidneys and testes increased significantly. The increased turnover of phospholipids in liver and heart was mainly due to increased turnover of phosphatidyl choline (PC) and phosphatidyl ethanolamine in liver and PC in heart. Turnover of phospholipids of testes was not affected.     

Changes in the erythrocyte in liver cirrhosis: role of cholesterol and plasma phospholipids

To investigate the role played by plasmatic lipids in the altered erythrocyte deformability observed in cirrhotic patients we studied 15 patients with liver cirrhosis (histologically diagnosed) and 10 healthy volunteers. Erythrocyte filtration time, plasmatic free and esterified cholesterol and phospholipids were measured in all subjects. The erythrocyte filtration time resulted to be significantly increased in cirrhotic patients (35' +/- 3, 35 M +/- SEM) when compared to control subjects (26' +/- 2, 53: M +/- SEM) (t = 2,078 p less than 0,05). This increase correlated in cirrhotic patients (but not in control subjects) with free/esterified cholesterol ratio (p less than 0,01) as well as free cholesterol/phospholipid ratio (p less than 0,001). Our results confirm that decreased erythrocyte deformability in cirrhotic patients which is accompanied by altered erythrocyte morphology is due, at least in part, to the altered lipids blood levels.