Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats

The effects of dietary powdered green tea (PGT) and theanine on in vivo hepatoma growth and cancerous hyperlipidemia were investigated in rats that had been implanted with a rat ascites hepatoma cell line of AH109A cells. The hepatoma-bearing rats were fed with a 20% casein diet (20C), 20C containing 2% PGT, or 20C containing 0.1% theanine for 14 days. Dietary PGT significantly and time-dependently reduced the solid tumor volume and weight as did dietary theanine. The hepatoma-induced endogenous hyperlipidemia, which was characterized by rises in the serum cholesterol (hypercholesterolemia) and triglyceride (hypertriglyceridemia) levels, was significantly suppressed by PGT and theanine supplementation. Bile acid excretion into the feces was significantly higher in the PGT- and theanine-fed rats than in the control rats. This inhibition of hypercholesterolemia may have resulted from tumor growth suppression as well as increased excretion of steroids from the body. These results suggest that PGT had both anti-proliferative activity toward hepatoma cells and hypolipidemic activity in the hepatoma bearing rats. They also suggest that theanine was, at least in part, responsible for the PGT actions.     

Effect of dietary fish oil on selected inflammatory markers in pigs

The present study tested a hypothesis that dietary fish oil (eicosapentaenoic acid+docosahexaenoic acid) in a commonly achievable dose ameliorates a systemic inflammation in pigs. Two groups of pigs of 16 animals each were fed a diet with either 2.5% of fish oil (F) or a control diet with 2.5% of palm oil (P). After 70 days of fattening, eight F and eight P pigs were challenged (F⁺; P⁺) i.v. by lipopolysaccharide. After 3 h, all pigs were sacrificed and blood, liver and visceral adipose tissue (VAT) samples were taken. No significant effect (P>0.05) of dietary oil on the feed intake and daily weight gain was found out. Less neutrophils (16.8% v. 28.8%; P<0.05) were found in the F⁺-leukocytes of the peripheral blood; F⁺ pigs had lower (P<0.05) percentage of the swine leukocyte antigen-D-related CD163⁺ (SLA-DR⁺ CD163⁺) macrophages in the VAT (15.4% v. 21.8%) and lower expression of the SLA-DR-CD163⁺ surface molecules of the VAT macrophages. No difference (P>0.05) between F⁺ and P⁺ pigs in the peroxisome proliferator-activated receptor γ, GPR120, Adipor1 and Adipor2 (adiponectin receptor) gene expression, respectively, was established; plasma adiponectin was the same (21.1 ng/ml) in F⁺ and P⁺ pigs. In comparison with the P⁺ pigs, increased expression of the lipopolysaccharide-binding protein (LBP) gene and intercellular adhesion molecule 1 (ICAM1) gene was found out in the liver of the F⁺ pigs; expression of the tumor necrosis factor α (TNFα) gene was higher in the liver but lower in the VAT of the F⁺ pigs (P<0.05). The F⁺ pigs had higher (P<0.05) plasma concentration of both anti-inflammatory cytokine interleukin-4 (0.46 v. 0.04 ng/ml) and pro-inflammatory TNF-α (13.41 v. 7.72 ng/ml). It was concluded that dietary fish oil at the tested amount had a negligible effect on expression of the evaluated receptor genes and plasma adiponectin, and had an ambiguous effect on expression of cytokine genes and plasma cytokine levels.     

Effect of cyclooxygenase genotype and dietary fish oil on colonic eicosanoids in mice

Dietary ω3 fatty acids can modulate substrate availability for cyclooxygenases (COXs) and lipoxygenases, thus modulating downstream eicosanoid formation. This could be an alternative approach to using nonsteroidal anti-inflammatory drugs and other COX inhibitors for limiting Prostaglandin E(2) (PGE(2)) synthesis in colon cancer prevention. The aims of this study were to evaluate to what extent COX- and lipoxygenase-derived products could be modulated by dietary fish oil in normal colonic mucosa and to evaluate the role of COX-1 and COX-2 in the formation of these products. Mice (wild-type, COX-1 null or COX-2 null) were fed a diet supplying a broad mixture of fatty acids present in European/American diets, supplemented with either olive oil (oleate control diet) or menhaden (fish) oil ad libitum for 9-11 weeks. Colonic eicosanoid levels were measured by liquid chromatography tandem mass spectroscopy (LC-MS/MS), and proliferation was assessed by Ki67 immunohistochemistry. For the dietary alteration of colonic arachidonic acid: eicosapentaenoic ratios resulted in large shifts in formation of COX and lipoxygenase metabolites. COX-1 knockout virtually abolished PGE(2) formation, but interestingly, 12-hydroxyeicosatetraenoic (12-HETE) acid and 15-HETE formation was increased. The large changes in eicosanoid profiles were accompanied by relatively small changes in colonic crypt proliferation, but such changes in eicosanoid formation might have greater biological impact upon carcinogen challenge. These results indicate that in normal colon, inhibition of COX-2 would have little effect on reducing PGE(2) levels.     

Effect of dietary fish oil (active EPA-30) on liver phospholipids in young and aged rats.

We explored the uses of fish oil (active EPA-30) as a source of eicosapentaenate (EPA; 20:5 n-3), to young and old rats. We treated three subgroups of rats each comprising 20 young or old rats, respectively. The first group was kept on the basal ration (lab-pellet) as control diet, the second group was fed semi-purified diets contained 5% pig-fat (n-3 fatty acids deficient diet). The third group was fed a modified diet in which 50% of pig-fat was replaced by active EPA-30. Livers of young rats fed pig-fat had a drastic decrease in the amount of phosphatidylethanolamine (PE) and omega-3 polyunsaturated fatty acids (EPA, 20:5 n-3 and docosahexaenoic, DHA, 22:6 n-3) and compensatory increase of phosphatidylcholine, saturated fatty acids and n-6 polyunsaturated fatty acids in the liver phospholipids. In contrast, the liver of young rats fed active EPA-30 had large amounts of PE and concomitant enrichment in polyunsaturated fatty acids. The liver of old rats, fed on active EPA-30 supplemented diet had lower amounts of PE and there were no significant changes in the phospholipid fatty acid composition.     

Effect of dietary fish oil on lung lipid profile and hypoxic pulmonary hypertension

The effects of dietary polyunsaturated fats on chronic hypoxic pulmonary hypertension were assessed in rats fed fish oil, corn oil, or a lower fat, "high-carbohydrate" diet (regular) beginning 1 mo before the start of hypoxia (0.4 atm, n = 30 for each). Mean pulmonary arterial pressures were lower in the chronically hypoxic rats fed fish oil (19.7 +/- 1.8 mm Hg) than in the rats fed corn oil (25.3 +/- 1.6 mm Hg) or regular diets (27.5 +/- 1.5 mm Hg, P less than 0.05). The fish oil diet increased lung eicosapentaenoic acid 50-fold and depleted lung arachidonic acid 60% (P less than 0.0001 for each). Lung thromboxane B2 and 6-ketoprostaglandin F1 alpha levels were lower, and platelet aggregation, in response to collagen, was reduced in rats fed fish oil. Chronically hypoxic rats fed fish oil had lower mortality rates than the other hypoxic rats. They also had lower blood viscosity, as well as less right ventricular hypertrophy and less peripheral extension of vascular smooth muscle to intra-acinar pulmonary arteries (P less than 0.05 for each). The mechanism by which dietary fish oil decreases pulmonary hypertension and vascular remodeling during chronic hypoxia remains uncertain. The finding that a fish oil diet can reduce the hemodynamic and morphological sequelae of chronic hypoxia may have therapeutic significance.     

Effect of dietary supplementation with a fish oil concentrate on the alkenylacyl class of ethanolamine phospholipid in human platelets

It has been demonstrated that the alkenylacyl class of ethanolamine phospholipid (PE) represents one of the major forms of eicosapentaenoic acid (EPA)-containing phospholipid in the circulating platelets isolated from human subjects consuming a fish oil concentrate. Since the alkenylacyl PE from human platelets is enriched in the eicosanoid precursor arachidonic acid (AA) and the n-6 polyunsaturate adrenic acid (AdA), it was of interest to study changes in alkenylacyl PE fatty acid composition upon fish oil supplementation. Healthy volunteers were given 20 capsules of MaxEPA daily (3.6 g of EPA plus 2.4 g of docosahexaenoic acid, DHA) for 6 weeks followed by a 6-week recovery period. Washed platelet suspensions were prepared and the fatty acid compositions of the phospholipid components were evaluated by thin-layer and gas-liquid chromatography at weeks 0, 3, 6, 9, and 12. Fatty acid composition changes were more pronounced in the alkenylacyl PE than in other platelet phospholipids as a result of fish oil consumption. The alkenylacyl PE exhibited a greater drop (by 20.3 mol%, i.e., from 72.0 to 51.7 mol%) in AA than diacyl PE (by 1.6 mol%) or total (predominantly diacyl) choline phospholipids (PC) (by 4.5 mol%). In alkenylacyl PE, the predominant reservoir of AdA in human platelet phospholipid, a dramatic reduction in the level of AdA also resulted with MaxEPA supplementation (from 7.9 to 3.1 mol%); diacyl PE and total PC decreased by 0.6 and 0.3 mol%, respectively. With respect to the n-3 fatty acids, EPA rose by 12.5 mol% in alkenylacyl PE, compared to only 3.8 and 2.5 mol% in diacyl PE and total PC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of hyperlipidemia in the LA/N-corpulent rat by dietary fish oil containing n-3 fatty acids

The LA/N rat, when homozygous for the corpulent gene (cp/cp), is obese, hyperphageous, hyperinsulinemic, hypertriglyceridemic and prone to the development of vascular and myocardial lesions. The hypertriglyceridemia, which in 3-month-old cp/cp males is 282 +/- 42 mg/dl and in females, 512 +/- 83 mg/dl, results from the presence of a large triacylglycerol-rich VLDL. The moderate hypercholesterolemia in these animals is largely due to markedly elevated HDL levels, which reach 172 +/- 21 mg total lipid/dl in males and 154 +/- 22 mg total lipid/dl in females. The LA/N-cp rat is thus an interesting animal model of endogenous hypertriglyceridemia in which to examine the hypolipidemic effects of pharmacological agents and also dietary oil supplements containing the n-3 fatty acids. In this study, 1-month-old male and female cp/cp rats were fed a normal low fat laboratory chow supplemented with either 10% olive oil or 10% redfish (Sebastes marinus) oil ad libitum for a period of 2 months. The redfish oil contained 4.9 +/- 0.1% of its total fatty acids as eicosapentaenoic (20:5(n-3)) and 2.3 +/- 0.5% as docosahexaenoic acid (22:6(n-3)), the predominant fatty acids being gondoic (20:1(n-3)), 21.9 +/- 0.9% and cetoleic acid (22:1(n-11)), 21.7 +/- 1.7%, which are of dietary origin. Daily caloric intake was similar to the oil-fed versus control rats. However, the oil-fed animals weighed significantly more than the controls after 2 months of oil supplementation. Redfish oil reduced serum triacylglycerols by 54% in males and 45% in females after 2 months. VLDL levels, after the same time period, were reduced by 44% in males and 39% in females. HDL lipid mass was significantly reduced in both sexes (by 27% in males and 49% in females). However, the levels remained above those of male LA/N +/+ rats of the same age and Long-Evens rats. Olive oil feeding significantly reduced serum cholesterol, triacyglycerols and phospholipids in male but only cholesterol and phospholipids in female animals. This oil had no significant effect upon VLDL total lipid levels in either sex, but significantly increased the particle diameter with a concomitant reduction in the cholesterol and phospholipid content. HDL total lipid levels were unaffected: However, HDL total cholesterol increased significantly in males only. Both oils markedly reduced serum LDL levels in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interactions of dietary lead with fish oil and antioxidant in chicks

Two experiments were conducted with day-old broiler chicks reared to 18 or 19 d of age. The objectives were: (1) to examine the effects of the antioxidant ethoxyquin (EQ) on peroxidation in feeds containing fish oil (FO) or lead (Pb), and (2) to determine whether systemic effects of Pb, which are attributed to tissue peroxidation, can be reversed by dietary EQ. Experiment 1 was a 2 x 2 factorial arrangement with the factors being 4% dietary cottonseed oil (CSO) vs FO and dietary Pb as lead acetate trihydrate (0 vs 1000 ppm). Feed was mixed 1 d prior to initiation of the experiment and stored at 4 degrees C until it was placed in the feeders. Experiment 2 was a 2 x 2 x 2 factorial arrangement with the factors being 3.5% dietary oil (CSO vs FO), dietary Pb (0 vs 1000 ppm), and EQ (0 vs 75 ppm). Feed was mixed 1 d prior to initiation of the experiment and held at room temperature thereafter. Growth depression by FO and Pb was less pronounced in Experiment 1 than in Experiment 2. In Experiment 2, FO and Pb increased the concentration of feed peroxide, and the increases were prevented by EQ. The growth depression by FO was completely reversed by EQ. EQ reversal of Pb-induced growth depression, although substantial, was not complete. The FO diet without Pb had a peroxide content (12.4 meq/kg feed) similar to the CSO + Pb diet (12.3 meq/kg feed); however, growth was not similar (407 vs 213 g body weight at 19 d, respectively). The results suggest that the toxic effects of Pb are mediated by peroxidative alterations both in the feed and in tissues. The ability of EQ to reverse significantly Pb effects on growth suggests a systemic action of this antioxidant.     

Effect of increasing amounts of dietary fish oil on brain and liver fatty composition

Increasing dietary fish oil in rat had the following effect on brain lipids: Arachidonic acid regularly decreased; eicosapentanenoic acid, normally nearly undetectable, was present; 22:5(n - 3), dramatically increased but remained below 1% of total fatty acids; cervonic acid was increased by 30% at high fish oil concentration. Saturated and monounsaturated fatty acids were not affected regardless of chain-length. In contrast, in the liver, nearly all fatty acids (saturated, monounsaturated and polyunsaturated) were affected by high dietary content of fish oil, but liver function was normal: serum vitamin A and E, glutathione peroxidase, alkaline phosphatase, transaminases were not affected. Serum total cholesterol, unesterified cholesterol and phosphatidylcholine were slightly affected. In contrast, triacylglycerols were dramatically reduced in proportion to the fish oil content of the diet.     

Effects of dietary fish oil and corn oil on rat mammary tissue

The effects, on the maternal mammary gland, of diets containing similar lipid percentages but differing in composition of polyunsaturated fatty acids (PUFA) have been assessed in rats during pregnancy and lactation. For this purpose, tuna fish oil (an n-3-PUFA-enriched oil) and corn oil (an n-6-PUFA-enriched oil) were included in diets at ratios such that the caloric inputs were the same as that of the control diet. As expected, the maternal diet affected the tissue composition of dams. Unexpectedly, only the tuna fish oil diet had an effect on pup growth, being associated with the pups being underweight between the ages of 11 and 21 days. The maternal mammary gland of rats fed the tuna fish oil diet displayed two main modifications: the size of cytoplasmic lipid droplets was increased when compared with those in control rats and the mammary epithelium showed an unusual formation of multilayers of cells. These results show that the tuna fish oil diet, during pregnancy and lactation, exerts specific effects on mammary cells and on the formation of lipid droplets. They suggest that this maternal diet affects the functioning of the mammary tissue.     

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.     

Appearance of hybridoma growth factor/interleukin-6 in the serum of mice bearing a methylcholanthrene-induced sarcoma

Serum concentrations of hybridoma growth factor/interleukin-6 progressively increased in mice bearing a transplantable methylcholanthrene-induced sarcoma with tumor growth. Elevated HGF/interleukin-6 concentrations were also positively correlated with increased serum concentrations of the hepatic acute phase reactant protein, amyloid P. Daily Indomethacin treatment of sarcoma-bearing mice prolonged survival and reduced the magnitude of the serum amyloid P response, but failed to attenuate either tumor growth or serum HGF/interleukin-6 responses. Since previous studies have demonstrated that neither interleukin-1 nor tumor necrosis factor-alpha can be detected in the serum of these sarcoma-bearing mice, and that HGF/interleukin-6 is a principal mediator of the hepatic acute phase response, we conclude that circulating HGF/interleukin-6 may contribute significantly to the host responses which accompany experimentally-introduced cancer. Furthermore, prostanoid inhibition does not appear to regulate the synthesis and release of HGF/interleukin-6 during tumor growth.     

Effect of dietary tin deficiency on growth and mineral status in rats

To clarify the influence of dietary tin deficiency on growth and mineral status, the following two different synthetic diets were fed to male Wistar rats: group 1—a diet containing 1.99 μg tin/g; group 2—a diet containing 17 ng tin/g. The rats in group 2 showed poor growth, lowered response to sound, and alopecia, with decreased food efficiency compared with rats in group 1. The changes of mineral concentrations in tissues observed in group 2, compared with group 1, are summarized as follows: calcium concentration in lung increased; magnesium concentration in lung decreased; iron concentrations in spleen and kidney increased; iron concentration in femoral muscle decreased; zinc concentration in heart decreased; copper concentrations in heart and tibia decreased; manganese concentrations in femoral muscle and tibia decreased. These results suggest that tin may be essential for rat growth.     

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.     

Lifelong exposure to dietary fish oil alters macrophage responses in Walker 256 tumor-bearing rats

Supplementation of the diet with fish oil (FO) decreases growth of the Walker 256 tumor and decreases the cachexia associated with tumor-bearing. The mechanisms by which FO inhibits tumor growth and cachexia are unknown. Macrophages are very important in host defence against tumors since they produce several anti-tumor agents which in turn have been shown to be modified by dietary FO, but rarely in the setting of tumor bearing and never in relation to lifelong exposure. In this study, we compared the effects of supplementation of the diet of pregnant and lactating rats and subsequent supplementation of the offspring with coconut fat or FO on macrophage activities involved in anti-tumor defence. FO supplementation was able to induce an increase in phagocytosis, in O2-, H2O2, nitric oxide, and TNF-alpha production by macrophages and in lysosomal volume in non-tumor-bearing rats. However, phagocytosis, production of O2- and H2O2 and lysosomal volume were not affected by the FO diet when rats were bearing tumors, although nitric oxide production was higher in these animals. It appears that tumor bearing activates the innate immune system and that dietary FO has little effect on innate immunity in the presence of Walker 256 tumors. Thus, it is still unclear how FO decreases the growth of Walker 256 tumors and the associated cachexia.     

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 dietary tin deficiency on growth and mineral status in rats.

To clarify the influence of dietary tin deficiency on growth and mineral status, the following two different synthetic diets were fed to male Wistar rats: group 1--a diet containing 1.99 micrograms tin/g; group 2--a diet containing 17 ng tin/g. The rats in group 2 showed poor growth, lowered response to sound, and alopecia, with decreased food efficiency compared with rats in group 1. The changes of mineral concentrations in tissues observed in group 2, compared with group 1, are summarized as follows: calcium concentration in lung increased; magnesium concentration in lung decreased; iron concentrations in spleen and kidney increased; iron concentration in femoral muscle decreased; zinc concentration in heart decreased; copper concentrations in heart and tibia decreased; manganese concentrations in femoral muscle and tibia decreased. These results suggest that tin may be essential for rat growth.