Geza Bruckner

The effects of fish oil and isoflavones on delayed onset muscle soreness.

INTRODUCTION/PURPOSE Fish oils (FO) have been shown to modulate the inflammatory response through alteration of the eicosanoid pathway. Isoflavones (ISO) appear to reduce the inflammatory pathway through their role as a tyrosine kinase inhibitor. Delayed onset muscle soreness (DOMS) develops after intense exercise and has been associated with an inflammatory response. Therefore, we hypothesized that physical parameters associated with DOMS could be decreased via the modulation of the inflammatory response by supplementing subjects with either FO or ISO. METHODS 22 subjects were recruited and randomly assigned to one of three treatment groups: FO (1.8 g of omega-3 fatty acids x d(-1)), ISO (120 mg soy isolate x d(-1)), or placebo (PL) (Western fat blend and/or wheat flour). All treatment groups received 100-IU vitamin E x d(-1) to minimize lipid peroxidation of more highly unsaturated fatty acids. Subjects were supplemented 30 d before the exercise and during the week of testing and were instructed to refrain from unusual exercise. DOMS was induced by 50 maximal isokinetic eccentric elbow flexion contractions. Strength parameters, pain, arm circumference, and relaxed arm angle (RANG) were measured at 48, 72, and 168 h post exercise. Cortisol, creatine kinase (CK), interleukin-6 (IL-6), tumor necrosis factor (TNFalpha), malondialdehyde (MDA), and serum iron were measured before supplementation, after supplementation, and post exercise. RESULTS Significant decreases were observed in RANG and strength 48 h postexercise among all groups, and there were significant increases in pain and arm circumference. There were no significant changes among all groups from baseline at 168 h (7 d) post exercise. There were no significant treatment effects between groups for the physical parameters or for cortisol, CK, IL-6, TNFalpha, MDA, or serum iron. CONCLUSION These data indicate FO or ISO, at the doses supplemented, were not effective in ameliorating DOMS with the above-cited protocol.

Fish oil increases peripheral capillary blood cell velocity in humans

Fish oils containing n-3 fatty acids have been shown in humans to decrease platelet aggregation in vitro, lower plasma triglycerides, and to increase bleeding time. The in vivo effects of fish oils on microcirculatory blood flow in humans has not been studied to date. Twenty-one male subjects were randomly assigned to either olive oil (n = 10) or fish oil (n = 11) supplemented groups to determine the effects of these oils on capillary blood flow velocity (CBV) in the nailfold area. The subjects were given the oils for three weeks (1.5 g oil/10 kg b.wt./day) in a single blind study design. In addition to CBV plasma lipid profiles, blood viscosity, blood pressure and platelet and erythrocyte fatty acids were also determined prior to and after the dietary intervention. Fish oil supplementation significantly increased CBV, by 1.75-fold (0.144 +/- 0.069 to 0.253 +/- 0.147 mm/s). The olive oil group remained unchanged. Increased levels of n-3 fatty acids were noted in platelets and erythrocytes of the fish compared to olive oil-supplemented groups. Blood viscosity was unaltered in both groups, however, blood pressure in the olive oil supplemented group was significantly decreased. Plasma triglycerides were significantly decreased in the fish oil supplemented group. These observations suggest that increases in CBV after fish oil supplementation are due to changes in vascular tone and not to alterations in blood pressure or blood viscosity.

Oxidative stress and antioxidant status in mouse kidney : Effects of dietary lipid and vitamin E plus iron

The purpose of this study was to determine the effects of dietary fat, vitamin E, and iron on oxidative damage and antioxidant status in kidneys of mice. Sixty 1-month-old male Swiss-Webster mice were fed a basal vitamin E-deficient diet that contained either 8% fish oil + 2% corn oil or 10% lard with or without 1 g all-rac-alpha-tocopherol acetate or 0.74 g ferric citrate per kilogram of diet for 4 weeks. Significantly (P < 0.05) higher levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), and conjugated dienes were found in the kidneys of mice fed with fish oil compared with mice fed lard irrespective of vitamin E status. Mice maintained on a vitamin E-deficient diet had significantly higher renal levels of TBAR, but not conjugated dienes, than the supplemented group. Fish oil fed mice receiving vitamin E supplementation had lower levels of alpha-tocopherol than did mice in the lard fed group. Significantly higher levels of ascorbic acid were also found in the kidneys of mice fed with fish oil than were found in mice fed lard. The levels of protein carbonyls and glutathione (GSH), and activities of catalase, superoxide dismutase, selenium (Se)-GSH peroxidase, and non-Se-GSH peroxidase were not significantly altered by dietary fat or vitamin E. Dietary iron had no significant effect on any of the oxidative stress and antioxidant indices measured. The results obtained provide experimental evidence for the pro-oxidant effect of high fish oil intake in mouse kidney and suggest that dietary lipids play a key role in determining cellular susceptibility to oxidative stress.

Isoflavone-rich soy isolate reduces lipid peroxidation in mouse liver.

The purpose of this study was to determine if an isoflavone-rich soy isolate affords protection against peroxidative damage in vivo. Weanling C57BL6 male mice were fed a basal diet (AIN-93G) supplemented with either nothing or 1.08 gram isoflavone-rich soy isolate/kg diet for 60 days. The soy isolate contained 400 mg/g isoflavone aglycones (226 mg/g genistein and 174 mg/g daidzein). Immediately following sacrifice liver was processed for measuring the levels of lipid peroxidation products, malondialdehyde (MDA) and conjugated dienes, and the levels of alpha-tocopherol, glutathione (GSH), and ascorbic acid, as well as the activities of catalase, selenium-dependent glutathione peroxidase (Se-GPx), selenium-nondependent glutathione peroxidase (non-Se-GPx), and superoxide dismutase (SOD). Compared with the control group, mice fed the diet supplemented with soy isolate had significantly (p<0.05) lower hepatic levels of MDA and conjugated dienes. The activities of catalase and SOD were significantly increased (p<0.05) in the liver of soy isolate-supplemented mice. The levels of vitamin E, GSH, and ascorbic acid and the activities of Se-GPx and non-Se-GPx were not significantly altered by the soy isolate. The results obtained provide experimental evidence that isoflavone supplementation confers protection against peroxidative damage to membrane lipids in vivo, possibly through enhancing the activities of the antioxidant enzymes catalase and SOD.

Lipoproteins, lipid droplets, lysosomes, and adrenocortical steroid hormone synthesis: Morphological studies

Recent studies concerning cellular cholesterol homeostasis suggest that there is a relationship between the serum lipoproteins (low density and high density lipoproteins: LDL and HDL), the intracellular storage of cholesterol (lipid droplets), lysosomes, and the steroidogenic activity of adrenocortical cells. This review surveys the current knowledge on cholesterol import from LDL/HDL by adrenocortical cells, its regulation, and the participation of lipid droplets and lysosomes in this process. The possible role of adrenocortical cell microvilli in the uptake of LDL/HDL is discussed. Under certain physiological, experimental, and pathological circumstances lysosomes accumulate unesterified and/or esterified cholesterol in the form of lipid‐lyososome complexes. As suggested by the data presented in this review, lipid‐lysosome complexes appear to be involved in cholesterol homeostasis, via altering lipid compartmentalization. Since previous reports do not clearly demonstrate a positive correlation between the volume of lipid‐ and lysosome‐ compartments and the rate of steroid hormone synthesis [for review, see Nussdorfer (1986) Int. Rev. Cytol., 98:1–405], the objective of this review is to provide a better understanding of the interactions of plasma lipoproteins, lipid droplets, lysosomes, and steroidogenesis. Microsc. Res. Tech. 36:480–492, 1997.

Microcirculation, vitamin E and omega 3 fatty acids: an overview.

We have observed significant increases in LDF and similar trends for CBV after FO supplementation in younger subjects (both normolipidemic and hyperlipidemic). In elderly subjects, this trend appears to be reversed unless subjects are supplemented with higher doses of vit. E (100 IU/10 KG/day). Our mouse data suggest that dietary vit. E at 100 IU/Kg does not adequately protect against lipid oxidation in vivo or in vitro following an oxidative insult when mice are fed an 8% FO & 2% linoleic acid containing diet. It has been reported that FO significantly lowers triglycerides and VLDL-cholesterol (especially where subjects have higher initial triglyceride values) and tends to increase LDL-cholesterol and Apo-B100. These findings are all the more important because the oxidation of LDL from FO-supplemented subjects caused a time-dependent increase in the ability to facilitate albumin transfer which was not diminished following a 2 month washout (WO). Addition of vit. E to the FO supplement prevented this change. These data suggest that FO supplementation without sufficient vit. E may be deleterious to the vascular endothelium. The western fat blend supplement appeared to be protective with increased length of supplementation most likely due to increased MONO fatty acids which are resistant to oxidation; vit. E supplementation appeared to have little additional effect. Our combined studies, and those reported by others, suggest that in humans, increased peripheral microcirculatory flow is most likely due to changes in precapillary vascular tone i.e., vasodilation. It is also possible that subtle changes in each of the three variables i.e. blood pressure, blood viscosity and vascular tone when combined may contribute to the significant changes which we have noted as increased LDF or CBV after intervention with dietary n-3 fatty acids. We hypothesize that interactions between dietary fatty acids and vit. E alters the ratios of vasoconstrictive-platelet aggegatory/vasodilatory-antiplatelet aggregatory agents (TXA2 and endothelin/PGI2 and nitric oxide), the expression of adhesion molecules (P-selectin and E-selectin) and thereby directly influences the modulation of free radical mediated events between blood elements and the vascular endothelium. Fatty acids of the n3 series may alter these events by favoring the production of vasodilatory compounds and decreased expression of P and/or E-selectins, provided that these highly oxidizable lipids are protected by adequate antioxidants.

Nutrition intervention to decrease symptoms in patients with advanced heart failure.

For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, and time to heart failure rehospitalization or all-cause death. The aims of this double blind-placebo controlled study are (1) to determine the effects of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue) and health-related quality of life at 3 and 6 months, and time to heart failure rehospitalization or all-cause death over 12 months from baseline; (2) compare dietary sodium intake, inflammation, and markers of oxidative stress between the nutrition intervention group and a placebo group at 3 and 6 months; and (3) compare body weight, serum lycopene, and erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3 and 6 months. A total of 175 patients with advanced heart failure will be randomized to either the nutrition intervention or placebo group.

Effect of adenosine and its metabolites on the hypothalamo-pituitary-adrenal axis

Adenosine (ADO) plays a key role in maintaining the energy charge of the cell and has been shown in vivo to stimulate hypothalamo-pituitary-adrenocortical (HPA) activity. The question arises as to whether these effects are related exclusively to ADO and/or its metabolic produces). Therefore, the present study was designed to test the in vivo effect of ADO and its phosphorylated or deaminated derivatives on plasma corticosterone concentration (PCC) in rats. ATP, ADP, AMP, ADO, inosine (INO), hypoxanthine (HYP), xanthine (XAN), and urate (URA) in solutions (40 μmol/100 g of metabolic body weight) were injected intraperitoneally, then 30 min later the animals were decapitated and the plasma samples were collected for corticosterone radioimmunoassay (RIA). Dose response curves for ADO and URA as well as a time course response for plasma URA and PCC following ADO administration were obtained. In addition, the effect of URA on the adrenocorticotrophic hormone (ACTH) secretion of AtT-20 pituitary cells in culture was determined. The results showed that not only ADO but the adenine nucleotides (AMP, ADP, ATP) and also the deaminated end-products (INO, XAN, URA) significantly increased PCC. HYP did not have any significant effect. The dose dependent effects of ADO and URA on PCC were significantly and highly correlated. URA stimulated ACTH secretion significantly in vitro in a dose-dependent manner, suggesting that ADO metabolites increase PCC via ACTH release. The possibility that ADO metabolites, principally URA, could be important signals for the HP A axis is discussed.

Adenosine inhibits the release of arachidonic acid and its metabolites (AAM) in activated human peripheral mononuclear cells.

Abstract.Objective:The effects of adenosine (Ado) and subtype-specific activators of adenosine receptors (A1, A2A, A2B and A3) were studied on the release of arachidonic acid (AA) and its metabolites (AAM) from human peripheral mononuclear cells (monocytes).Materials and method:Adenosine and the selective agonists and antagonists of adenosine receptors were used. 3H-AA and its metabolites released into the medium were determined by measurement of the total 3H radioactivity released without separating the AAM.Results:In the cells activated by protein kinase C specific phorbol ester (phorbol 12-myristate 13–acetate) and Ca2+ ionophore (A23187), adenosine and two subtype-specific receptor agonists, CPA(A1) and CGS 21680 (A2A) induced concentration-dependent inhibition of the release of AAM, whereas stimulation of A2B or A3 receptors was ineffective. The rank order of potency for the inhibition of AAM release was as follows: CGS 21680 = CPA > adenosine > NECA (in the presence of ZM 24185 and DPCPX as A2A and A1 adenosine receptor antagonists, respectively) = IB-MECA. Adenosine inhibited the release of AAM only at and above the concentration of 100 μM, whereas the inhibitory effect of A1 and A2A receptor specific agonists appeared at a concentration of 10-7 M.Conclusions:It can be concluded that adenosine physiologically may not have a significant effect on the AAM release of circulating monocytes, but in pathological conditions, where the local Ado concentrations increases, this nucleoside, through activation of A2A and A1 receptors can exert, at least in part, an antiinflammatory action by decreasing proinflammatory AAM production.

Effect of nutrients on plasma corticosteroid concentration in cold-stressed rats.

Little is known about the mechanisms as to how nutrients affect plasma corticosteroids in cold-stressed and starved animals. Therefore, cold-stressed rats (maintained at 7 degrees C) were fasted (control) or fed a balanced diet (casein 20 wt%, fat 5 wt%, starch 70 wt% and vitamin-mineral premix 5 wt%) or the following dietary nutrients for 72 h: casein, lard, starch, glycerol, stearic acid, leucine or glutamic acid. The animals were then killed and plasma corticosteroid concentrations (PCC) were determined. PCC were significantly reduced (p < 0.05) in cold-stressed animals fed a balanced diet (16.95 micrograms/100 ml plasma) compared to the fasted cold-stressed controls (FCSC) (24.16 micrograms/100 ml plasma). Additionally, corticosteroid concentrations (micrograms/100 ml plasma) of animals fed the following specific nutrients were also significantly lower than the FCSC values: starch (15.53), lard (12.01), stearic acid (12.74), glycerol (13.32) and leucine (16.03). Casein and glutamic acid did not significantly alter plasma corticosteroid levels relative to the FCSC concentration. It is concluded that certain specific building blocks of nutrient classes, i.e. stearic acid or glycerol, can alter PCC to the same extent as the parent compound (lard), however the individual components of casein, a complex nutrient, i.e. leucine, a ketogenic amino acid, versus glutamic acid, a glycogenic amino acid, may elicit a different PCC effect.