Biomedical subjects
Publications and source records attributed to S Mokady.
The fluidity of the erythrocyte membrane derived from growing rats raised under restricted food intake was found to be higher than the fluidity of the respective membranes from ad libitum fed animals. Considering the apparent relationship between the decrease in membrane fluidity and aging, the results point to the possible beneficial effects of food restriction at a young age.
The effect of dietary fish (mackerel) oil on the function and fluidity of the intestinal microvillus membrane in 1-y-old rats was compared with that of coconut and soybean oils. The animals were fed diets containing 10% protein (derived from casein) and 15% oil. Intestinal microvillus membranes and RBC ghosts were isolated after a 6-wk feeding period and examined for fluidity by fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene. The functionality of the microvillus membrane was assessed by the activity of the intrinsic enzyme alkaline phosphatase. No differences in the fluidity were observed between the microvillus membranes or between the RBC ghosts derived from the various dietary groups. The alkaline phosphatase activity of the microvillus membrane was found to be the lowest in the membranes isolated from the fish oil-fed rats. In these membranes the contents of 20:5(n-3) and 22:6(n-3) fatty acids were higher than in the membranes derived from the coconut and soybean oil-fed animals. The cholesterol to phospholipid molar ratio was lower in the coconut oil-fed group than in the other two groups. It is suggested that the compensatory effect of the elevated cholesterol to phospholipid molar ratio on the membrane fluidity was such that no differences in the overall fluidity were detected. It is likely that the incorporation of these long chain fatty acids might have caused compositional changes in the lipid microenvironment of the enzyme. Such changes could alter the fluidity of these microdomains, thereby affecting the activity of the integral enzyme alkaline phosphatase.
High plasma cholesterol levels and plasma lipid peroxidation are associated with atherosclerosis. The effect of excessive dietary tryptophan on plasma lipid peroxidation was studied in rats fed a diet containing soybean oil (control), as well as an atherogenic diet, containing coconut oil and cholesterol. Feeding the atherogenic diet resulted in a 5-fold increment in plasma cholesterol concentration with no significant effect of the tryptophan supplementation. The plasma obtained from the hypercholesterolemic rats exhibited a 67% increased lipid oxidation (measured as thiobarbituric acid reactive substances) in comparison to normocholesterolemic plasma. Dietary tryptophan supplementation increased plasma lipid peroxidation by 9 and 21% in the control and in the hypercholesterolemic animals, respectively. Similarly, the excessive dietary tryptophan enhanced macrophage cholesterol esterification rate by 40 and 38% following cell incubation with the plasma obtained from the control and from the hypercholesterolemic animals, respectively. Since tryptophan is the precursor of serotonin we have measured urine concentration of 5-hydroxyindoleacetic acid (5HIAA), the metabolite of serotonin, and found 22 and 118% elevation in 5HIAA in the tryptophan fed control and hypercholesterolemic rats, respectively. The direct effect of tryptophan and serotonin on in vitro lipid peroxidation was also studied. Low density lipoprotein (LDL) was peroxidized by incubation with copper ions in the presence of tryptophan or serotonin. Serotonin was shown to enhance LDL peroxidation whereas tryptophan had no effect on LDL peroxidation. We conclude that excessive dietary tryptophan may be atherogenic since it enhanced plasma lipid peroxidation in hypercholesterolemic rats and increased macrophage uptake of plasma cholesterol. These effects are probably associated with increased plasma concentration of serotonin following the consumption of a tryptophan supplemented diet.
The effect of various avocado oils on liver metabolism was studied in growing female rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined avocado oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by organic solvent extraction from intact fruit, or its unsaponifiable components, showed a significant increase in total liver lipogenesis as well as in phospholipid and triglceride synthesis. Rats fed avocado-seed oil exhibited enhanced [1-14C]acetate incorporation into total liver lipids but showed the same distribution of label in the three main lipid classes as that of rats fed refined avocado oil. In addition, a significant reduction of triglycerides and protein content of plasma very-low-density lipoprotein and high-density lipoprotein fractions was observed in rats fed avocado-seed oil as compared with rats fed refined oil. Electron micrographs suggested that the alterations in hepatic lipogenesis are related to the marked proliferation of the smooth endoplasmic reticulum, which is known to be associated with induction of enzymes involved with lipid biosynthesis. The differences between the animals fed seed oil and those fed the unrefined oils, in the distribution of label within the main lipid classes, indicate that more than one factor is involved in the alterations caused by these oils.
High plasma and tissue levels of beta-carotene have been implicated to be inversely related to the incidence of some types of cancer. Previous studies indicated that the availability of the natural beta-carotene isomer mixture of Dunaliella bardawil was severalfold higher than that of synthetic all-trans beta-carotene. This study illustrated that this higher availability, as expressed by hepatic and plasma beta-carotene, can be further enhanced by increased dietary lipid level. For 12 days, weanling male and female rats were fed diets containing either 0.1% all-trans beta-carotene or spray-dried Dunaliella bardawil having an equal level of the beta-carotene isomer mixture. The diets contained 5 or 15% soybean oil. The rise in dietary fat resulted in a marked increase in plasma and liver beta-carotene, with the Dunaliella isomer mixture being more effective. Higher levels were found in female than in male animals. These findings may be relevant when a high dose of beta-carotene is considered as a potential anticancer agent.
The effect of various avocado and soybean oils on collagen metabolism in the liver was studied in growing female rats for 8 weeks and in day-old chicks for 1 week. In comparison with rats fed either refined avocado oil, refined or unrefined soybean oils, rats fed unrefined avocado oil showed a significant decrease in total collagen solubility in the liver, while there were no changes in total collagen, protein and moisture content. Chicks fed unrefined avocado oil as compared to those fed refined avocado oil also showed a decrease in hepatic total soluble collagen while hepatic total collagen remained unaffected. Electron micrographs and light-microscope examinations of rats' liver revealed collagen accumulation in the periportal location. This is suggestive of the early stages of fibrosis.
The effects of various avocado oils on collagen metabolism in skin were studied in growing rats fed diets containing 10% (w/w) of the tested oils. Rats fed the unrefined avocado oil extracted with hexane from the intact fruit, its unsaponifiables or the avocado seed oil, showed significant increases in soluble collagen content in skin, though total collagen content was not affected. The increased soluble collagen content appears to be a consequence of the inhibition of lysyl oxidase activity. The active factor was found to be present in the unrefined avocado oil and probably originated from the avocado seed, since collagen metabolism was affected only by fractions which contained lipids fraction from the seed. In comparison rats fed the refined or unrefined soybean oils showed no effects.
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The fluidity of lipoproteins from normolipidemic subjects and from familial hypercholesterolemic patients was investigated by fluorescence polarization. The fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene) was incorporated into the lipoprotein fractions, and assessment of the fluidity pattern of each particle was determined by fluorescence anisotropy measurements over a temperature range of 10 to 40 degrees C. The very low density lipoprotein (VLDL) of the hypercholesterolemic patients was found to be considerably more rigid than the respective VLDL of normolipidemic subjects. Analysis of the constituents of the various lipoproteins suggested that the large difference in the fluidity between hypercholesterolemic and normal VLDL patients might be due to increased VLDL cholesterol/triglyceride, cholesterol/protein and cholesterol/phospholipid ratios, which were 10, 2 and 1.4 fold higher, respectively, in the hypercholesterolemic VLDL patients. Decreased VLDL fluidity in familial hypercholesterolemic patients may be of importance in the pathogenesis of their accelerated atherosclerosis.
The effect of riboflavin deficiency on the fluidity and function of the red blood cell (RBC) membrane and on the activity of some enzymes involved in antioxidant defense mechanisms was studied. Growing male rats were fed an experimental (riboflavin-deficient) or a control (riboflavin-supplemented) diet. Following 7 wk of feeding, RBC from riboflavin-deficient rats contained higher levels of peroxidation products, most likely due to decreased glutathione reductase activity. An elevation in glutathione peroxidase activity was also observed whereas the activity of catalase and superoxide dismutase was not affected. Membrane fluidity was studied by fluorescence polarization, using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. The fluidity of RBC membranes isolated from riboflavin-deficient rats was significantly lower than that of the controls. This decreased fluidity was accompanied by an increase in the activity of the membrane-bound enzyme acetylcholinesterase. This study demonstrated that a decrease in cells' ability to cope with peroxidative damage as a result of riboflavin deficiency may lead to changes in the fluidity and function of membranes.
Previous results indicated that beta-carotene, as present within the unicellular alga Dunaliella, accumulated in the liver of chicks to a much higher degree than did synthetic all-trans beta-carotene. Because the Dunaliella beta-carotene is composed of an approximately equal mixture of two stereoisomers, 9-cis and all-trans, we tested whether a similar mixture of purified beta-carotene isomers would yield comparable results. Indeed, analysis of liver following 2 wk of feeding show a 10-fold higher accumulation of beta-carotene in the chicks fed a mixture of purified 9-cis and all-trans beta-carotene as compared with those fed only all-trans beta-carotene. The ratio of 9-cis to all-trans beta-carotene in the liver was about three times higher than that present in the beta-carotene fed to the chicks. Retinol and retinyl esters accumulated to a similar degree in the livers of chicks given all treatments.
The effect of diets enriched with tryptophan (4 and 10 g/kg) on ADP induced platelet aggregation and on plasma lipids was studied with growing rats, following feeding periods of up to 3 weeks. Dietary tryptophan was found to enhance markedly ADP induced platelet aggregation. It appears that this effect was not related to plasma lipid levels. In vitro studies aimed to clarify the mechanism by which tryptophan exerts its action showed that the latter, at concentrations up to 100 micrograms/ml, had no effect on ADP induced platelet aggregation. On the other hand, serotonin, the metabolic product of tryptophan, increased the ADP induced platelet aggregation in a dose dependent pattern. The possible involvement of serotonin in the observed enhancement of platelet aggregation was further substantiated by the observed high levels of 5-hydroxyindole acetic acid, which is a catabolite of serotonin, in the urine of the experimental animals. It is conceivable that tryptophan enhances platelet aggregation in rats via its metabolite, serotonin, and this may in turn contribute to increased atheroslerotic risk.
Male rats aged 1, 9 and 19 months were used to study changes in membrane fluidity with age, employing the fluorescence polarization technique with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the fluorescent probe. The intestinal microvillus membranes derived from the 19-month-old rats were found to possess lower fluidity than that observed with the membranes derived from the younger animals. The decrease in fluidity with age was also reflected in a corresponding increase in the gel-to-liquid crystalline transition temperature. Only small insignificant changes with age, were observed in the fluidity of the red blood cell membrane.
The effects of various avocado oils on some liver characteristics were studied in growing rats. The rats were fed diets containing 10% (w/w) avocado oil for 4 wk. In comparison with rats fed refined oil obtained from cored fruit by centrifugal separation, rats fed unrefined avocado oil obtained by solvent extraction from the intact fruit, or refined avocado oil containing avocado-seed oil, showed significant growth inhibition, an increase in the amount of hepatic lipids (identified as steatosis by histopathological examination), and a decrease in levels of triglycerides in blood. Rats fed the refined oil containing unsaponifiable material prepared from unrefined oil from the intact fruit showed similar responses. Fatty livers were not induced by feeding rats unrefined avocado oil obtained from intact fruit by centrifugal separation, although a significant decrease in blood triglycerides was observed. There were no significant differences between groups in serum total protein, albumin or bilirubin content or in alanine aminotransferase activity. However, serum alkaline phosphatase activity was increased in rats fed the seed oil, the unrefined solvent-extracted oil from intact fruit, or the unsaponifiables, and aspartate aminotransferase activity was significantly increased in the group fed avocado-seed oil. These data suggest that consumption of avocado oil extracted from intact fruit may cause changes in liver metabolism.
The safety of the alga Dunaliella bardawil for food use, was evaluated in a multigeneration study with rats. Four generations were raised on diets containing 0, 5 or 10% dehydrated D. bardawil. Each experimental group comprised ten males and 20 females. No significant differences were observed between the rats consuming algae and the controls, of any generation, in general appearance, behaviour, growth, reproductive performance or gross pathology. The blood chemistry and haematology of the first generation animals, after 1 yr on the diets, showed no appreciable differences between the experimental and control animals. The only differences in histopathology observed were a decrease in some chronic inflammations and an increased frequency of focal bronchopneumonia in rats fed 10% algae compared with the controls. The latter effect may be attributed to the powdery nature of the algal diet. Considering the large amount of algae consumed by the experimental rats, and the absence of adverse effects in these animals, this multigeneration feeding study may be indicative of the safety of D. bardawil for human consumption.
1. The thermal properties of intestinal alkaline phosphatase were investigated with three species of deep-water fish in the temperature range of 0-70 C. 2. A relationship was found between the thermal stability of the enzyme and the fish origin. 3. Maximum activity of alkaline phosphatase of the fish that originated in tropical water, namely, Aphanopus carbo and Epigonus telescopus was 60 C, whereas the respective maximum enzyme activity of Etmopterus princeps that originated in the burial zone was 30 C. 4. A breakpoint at 10 degrees C in the Arrhenius plot of emzyme activity in the case of A. carbo and a lack of a break point in the case of E. telescopus and E. princeps, are in accordance with the stenothermic nature of the former and the everythermic nature of the two latter fish species.
1. Plasma lipoprotein separation by density gradient ultracentrifugation largely depends on visual examination based on the natural yellow pigments of lipoproteins. 2. In non-human species and in humans with dyslipoproteinemia, some lipoproteins are not well visualized due to the lack of pigments. 3. Using a fluorescent probe in minute quantity (1,6 diphenyl-1,3,5-hexatriene) we were able to demonstrate an effective plasma lipoprotein separation using a discontinuous density gradient ultracentrifugation technique. 4. Plasma lipoproteins of human, chicken, rat and carp were compared showing the unique character of carp HDL.
The unicellular halotolerant alga Dunaliella bardawil was previously shown to contain high concentrations of beta-carotene composed of about equal amounts of the all-trans and 9-cis isomers. One-d-old chicks and 7-wk-old male rats were fed diets supplemented with synthetic all-trans-beta-carotene or dry D. bardawil at equivalent levels of beta-carotene. The chicks were fed diets containing up to 0.025% beta-carotene for 2 mo, and the rats up to 0.1% beta-carotene for 2 wk. Liver analyses at the end of these periods indicated that both species showed at least a tenfold higher accumulation of the algal beta-carotene isomer mixture than of the synthetic all-trans-beta-carotene. The ratio of 9-cis-beta-carotene to the all-trans isomer in the livers of the algae-fed rats and chicks was similar to or higher, respectively, than that present in the algae. Retinol plus retinyl ester accumulated to a similar extent in the rats and chicks fed diets supplemented with synthetic all-trans or the natural isomer mixture of beta-carotene. The preferable accumulation of the natural isomer mixture of beta-carotene suggests that attention should be paid to the different sources of beta-carotene when testing their efficacy in effects other than providing retinol, such as in their possible role in the prevention of some types of cancer.