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Biomedical subjects

G A Boissonneault

Publications and source records attributed to G A Boissonneault.

At least 37 records · Page 2Linked to original sources
PubMed1990

Aging and endothelial barrier function in culture: effects of chronic exposure to fatty acid hydroperoxides and vitamin E.

As the endothelium ages it may become more susceptible to damage by atherogenic plasma components such as toxic lipid oxidation products. Vitamin E (vit E) might prove to be anti-atherogenic by reducing oxidative injury. This study investigated the effects of age and chronic exposure to fatty acid hydroperoxides (OFA) and/or vit E on endothelial barrier function (EBF) and cell growth characteristics. Chronic exposure to 5 microM OFA for 40 passages resulted in an age-related decrease in EBF, while supplementation of OFA-treated cultures with 25 microM vit E protected against the OFA-mediated decrease in EBF, independent of cell age. Vit E treatment alone had no significant effect on EBF relative to control cultures. No changes in growth characteristics, i.e., total DNA or protein per culture, were noted, regardless of treatment, although total DNA per culture decreased with increasing culture passage. These results suggest that chronic oxidative stress decreases EBF, predisposing the artery to infiltration by blood components and subsequent atherogenesis and that vit E delays cumulative changes in EBF related to chronic OFA exposure.

Aging↗
PubMed1990

The effect of the endophyte (Acremonium coenophialum) and associated toxin(s) of tall fescue on serum titer response to immunization and spleen cell flow cytometry analysis and response to mitogens.

Experiments were conducted with rats and mice to evaluate the effect of the consumption of endophyte (Acremonium coenophialum) and associated toxin(s) infected tall fescue on humoral and cellular aspects of immune function. Treatment diets were: (1) rodent chow (RC) or (2) rodent chow mixed 1:1 (w/w) with endophyte infected (E+) or (3) non-infected (E-) tall fescue seed. Rats fed the E+ diet in experiment 1 (43 days) exhibited a lower (P less than 0.05) serum titer to sheep red blood cell (SRBC) immunization than those fed the E- diet (38.4 vs 131.3). The E+ rats also had lower (P less than 0.01) white cell counts than either RC or E- groups (5225 vs 8959 and 7491/mm3). Spleen cells from mice fed the E+ diet for 37 days exhibited a reduced (P less than 0.05) response to the mitogens Concanavalin A and lipopolysaccharide. Flow cytometric analysis revealed a significant (P less than 0.01) 42% increase in T suppressor cell numbers in spleens of mice fed the E+ vs RC diets.

Acremonium↗
PubMed1990

Effect of vitamin E on linoleic acid-mediated induction of peroxisomal enzymes in cultured porcine endothelial cells.

Linoleic acid decreases endothelial barrier function in culture. We hypothesize that the mechanism may involve induction of peroxisomes, with subsequent generation of hydrogen peroxide, and that vitamin E may protect against barrier function loss by preventing the induction of peroxisomal enzymes. To investigate this hypothesis, we exposed cultured endothelial cells to 0 or 90 mumols/L linoleic acid [18:2(n-6)], with or without 25 mumols/L supplemental vitamin E, for 5 d. The induction of peroxisomes by linoleic acid exposure was determined by measuring cellular peroxisomal beta-oxidation and catalase activity. Vitamin E alone had no effect on beta-oxidation or catalase activity, whereas linoleic acid exposure significantly increased both compared with control values. Vitamin E supplementation prevented induction of peroxisomal beta-oxidation and catalase activity by 18:2. In contrast, cell enrichment with vitamin E had no effect on 18:2-induced accumulation of cytoplasmic lipid-like droplets. These results confirm our hypothesis that the protective effects of vitamin E against fatty acid-mediated endothelial cell injury may be due in part to the ability of vitamin E to prevent the induction of peroxisomal beta-oxidation enzymes and thus the formation of excess hydrogen peroxide.

Animals↗
PubMed1989

Effects of serum type on growth and permeability properties of cultured endothelial cells.

Serum is frequently added to defined basal media as a source of certain nutrients and macromolecular growth factors essential for cell growth. The many different sera commercially available may not be equally suitable for all cell types. The effects of four sera, fetal bovine serum (FBS), calf bovine serum (CS), equine serum (ES-1), and plasma-derived equine serum (ES-2), on growth and permeability properties of cultured porcine endothelial cells were determined. The rate of DNA synthesis, measured as [3H]thymidine incorporation, reached a peak at around 24 h, regardless of serum type, and was most marked with ES-1- or ES-2-treated cells. However, when estimated by total DNA, FBS, CS, or ES-1 treatment resulted in greater cell proliferation than ES-2. Based on protein synthetic rate and total cell protein, both FBS and CS appeared to be most growth supporting. At 72 h after cell plating, albumin passage across cultured endothelial monolayers was elevated in ES-1- and ES-2-treated cells compared with FBS- or CS-treated cells. "Leaky" cell monolayers were most marked with ES-1-treated cells. Cells grown in ES-2- and particularly in ES-1-enriched media were larger and more spindle-shaped compared with the typical cobblestone appearance of cells cultured in media enriched with either FBS or CS. These data suggest that CS, but not ES-1 or ES-2, is an excellent substitute for FBS to support desirable growth properties of macrovascular endothelial cells in culture.

Animals↗
PubMed1989

Protective effects of vitamin E in age-related endothelial cell injury.

Age is strongly correlated to the onset of atherosclerotic lesion formation in humans. This may be associated with an age-related increase in the susceptibility of the vascular endothelium to oxidative injury. Such injury may result in altered endothelial function as a barrier to plasma components, such as cholesterol-rich lipoprotein remnants. To investigate this hypothesis, the relationship between endothelial cell culture age, susceptibility to oxidative injury and protection against this injury by the nutrient/antioxidant vitamin E on endothelial barrier function (transfer of albumin across endothelial monolayers) was examined. An acute 24 h exposure to 30 microM linoleic acid hydroperoxide resulted in increased albumin transfer at all cell passages tested (up to passage 50). Pre-enrichment of cells with 25 microM vitamin E always protected endothelial cells against oxidized fatty acid-induced cell injury, independent of cell age. In comparison, patterns of total cell protein and DNA were not markedly influenced by experimental treatments, although age-related declines in total DNA were noted. These data suggest that the possible correlation between age and the onset of atherosclerosis may be in part related to a decrease in endothelial barrier function due to oxidative stress, permitting more blood components to enter the arterial wall. Furthermore, vitamin E may protect endothelial cells against oxidant-mediated vascular injury.

Aging↗
PubMed1988

Effect of vitamin E on oxysterol- and fatty acid hydroperoxide-induced changes of repair and permeability properties of cultured endothelial cell monolayers.

Oxidation products of fatty acids (fatty acid hydroperoxides) or of cholesterol (oxysterols) may be atherogenic by being injurious to the vascular endothelium. Vitamin E may protect cells against such injury by acting as an antioxidant and by regulating cell growth and/or repair. As indices of proliferation and growth/repair, synthesis of DNA [3H]thymidine incorporation) and protein ([3H]leucine incorporation), as affected by exposure to linoleic acid hydroperoxide (18:2-OOH), cholestan-3 beta, 5 alpha, 6 beta-triol (Triol), and/or alpha-tocopherol, was determined in confluent vascular endothelial cell cultures. Cell injury was assessed by measuring the passage of albumin through a cultured endothelial monolayer. Exposure to either Triol or 18:2-OOH significantly increased the rate of albumin transfer across endothelial monolayers. Prior enrichment with vitamin E protected endothelial cells from injury by 18:2-OOH but not Triol. Cell exposure to 25 microM vitamin E increased DNA synthesis compared with control cultures. DNA synthesis was also elevated in 18:2-OOH exposed cells, whereas Triol had no effect on cell replication. Prior cell exposure to vitamin E prevented the marked increase in DNA synthesis seen with 18:2-OOH. Protein synthesis was increased by 18:2-OOH, but not by Triol or vitamin E treatment. These results show that 1) both Triol and 18:2-OOH are cytotoxic, 2) vitamin E stimulates cell proliferation, 3) vitamin E protects cells against 18:2-OOH- but not Triol-induced cell injury (i.e., increased permeability to albumin), and 4) endothelial cell damage initiated by 18:2-OOH, but not Triol, stimulates synthesis of DNA and protein in an attempt to divide and repair the injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cholestan-3 beta,5 alpha,6 beta-triol decreases barrier function of cultured endothelial cell monolayers.

Cholesterol oxidation products (oxysterols) found in foods may be atherogenic, possibly by altering the barrier function of the vascular endothelium. To investigate this hypothesis, endothelial cells were cultured on micropore filters and the effect of cholesterol and the oxysterol cholestan-3 beta,5 alpha,6 beta-triol (Triol) on albumin transfer across cultured vascular endothelial monolayers (ECM) was studied. Exposure to Triol significantly increased albumin transfer across ECM. The effect of Triol on endothelial cell barrier function was time and concentration dependent, with maximum albumin transfer being reached at 20 microM Triol and after a 24-h exposure. Pure cholesterol, on the other hand, did not affect albumin transfer at concentrations as high as 130 microM. Although an increase in albumin transfer across ECM was observed after a 2-h incubation with Triol-enriched media, a 24-h incubation period was necessary to cause a significant release of cellular lactate dehydrogenase (LDH) into the culture media. Morphological perturbations of the cell monolayers were observed at approx. 14-18 h after cell exposure to Triol-enriched media. Enrichment with cholesterol or vitamin E did not prevent the Triol-induced increase in albumin transfer across ECM. These results suggest that exposure to oxidized cholesterol, but not cholesterol, itself, reduces the ability of the endothelium to act as a selectively permeable barrier to plasma components, and that these events may not be prevented by cholesterol or vitamin E.

Albumins↗
PubMed1986

Dietary fat and neoplasia--the role of net energy in enhancement of carcinogenesis: effects of fat and calories on the immune system.

The mechanism by which carcinogenesis is enhanced by dietary fat is not understood. We know that a minimum level of essential fatty acids (EFA) is necessary for mammary tumor development and that this level probably exceeds the normal requirements of rats. Once the minimum level of EFA has been supplied, the calorie contribution of dietary fat may account for its enhancement of carcinogenesis. In this regard, we must recognize that the efficiency with which dietary energy is utilized is known to increase as the fat content of the diet is raised. Hence even when fed isocalorically to low fat diets, high fat diets will provide more net energy. Modulation of host immunity has been proposed as a mechanism of action of both fat and calorie intake on neoplasia. We review the literature examining the effects of fat and calories on the cell-mediated immune system, that arm of the immune system most directly responsible for the killing of neoplastic cells.

Dietary Fats↗
PubMed1986

Modulation of carcinogenesis by dietary factors.

The purpose of this report is to present recent data on two modulating factors of carcinogenesis that are found in Western-type diets: a beef-derived mutagenesis modulator that has been shown to inhibit the initiation of epidermal carcinogenesis in mice, and the possible role of net energy rather than dietary fat per se in the enhancement of rat mammary carcinogenesis.

Animals↗
PubMed1986

Net energy effects of dietary fat on chemically induced mammary carcinogenesis in F344 rats.

The effect of net energy, as distinct from kilocalorie intake or the percent of fat in the diet, on 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced mammary tumorigenesis in female inbred F344 rats was investigated. Rats were fed a 5% corn oil diet from weaning until DMBA administration, when they were switched to one of three dietary regimens: 5% corn oil diet, low-fat diet fed ad libitum (LF); 30% corn oil diet, high-fat diet fed ad libitum (HF); or 30% corn oil diet fed at a level providing a calculated net energy equivalent to the group on LF [high-fat diet fed at a restricted level (HF-R)]. Calculated relative net energy values of the amounts of diet actually consumed by the groups on HF-R, LF, and HF were, respectively, 0.90, 1.00, and 1.07 (kcal equivalent to 34.1, 42.2, and 40.8, respectively). Weight gain for the groups on LF and HF-R was the same throughout the experiment (24 wk), while rats on HF weighed significantly more at 6 weeks and thereafter. Body composition analyses at 24 weeks established that the groups on HF and HF-R were equivalent in fat: protein ratio, whereas the group on LF had about 35% less body fat and 15% more body protein. Carcass energy was in the following order for rats in these diet groups: HF greater than HF-R greater than LF. At 24 weeks, tumor incidences for the groups on HF, LF, and HF-R were, respectively, 73, 43, and 7%. These data indicated that tumor appearance does not depend on the percent fat in the diet per se but rather on a complex interaction involving energy intake, energy retention, and body size.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

25-Hydroxycholesterol-induced elevations in 45Ca uptake: permeability changes in P815 cells.

Certain oxysterols are capable of suppressing the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. We have previously demonstrated that treatment of P815 cells with 1 microgram 25-hydroxycholesterol/ml culture results in a rapid influx of 45Ca, and supplemental cholesterol prevents this from occurring. In this paper, we report on investigations into the means whereby this influx of calcium takes place. Through the use of respiratory inhibitors which prevent mitochondrial retention of calcium it was determined that the large increase in slow phase (intracellular) calcium uptake caused by 25-hydroxycholesterol treatment was related to mitochondrial uptake. The effects of various inhibitors of calcium uptake into cells, including verapamil, diltiazem, quinidine, ruthenium red, Co++, Mn++, were tested. Of these only Co++ and ruthenium red had any effect on 45Ca uptake. 25-Hydroxycholesterol has been shown to be capable of membrane insertion and this could result in plasma membrane permeability changes. To test this hypothesis P815 cells were treated with 1 microgram 25-hydroxycholesterol/ml or 5 micrograms mevinolin/ml culture. Mevinolin, being a water soluble competitive inhibitor of HMG-CoA reductase, should be unable to disrupt membrane architecture in a manner analogous to 25-hydroxycholesterol. While both inhibitors rapidly suppressed the synthesis of digitonin-precipitable sterols, only 25-hydroxycholesterol was able to increase 45Ca influx. The implications of these findings are discussed.

Animals↗
PubMed1985

Effects of p-aminobenzoic acid, methionine, threonine and protein levels on susceptibility of mice to Plasmodium berghei.

The effects of dietary p-aminobenzoic acid (PABA), protein, methionine and threonine on Plasmodium berghei infection in mice were investigated. Animals were fed diets containing 12 or 20% casein supplemented with PABA (0 or 2 mg/kg diet), methionine (0 or 15 mg/g casein) and threonine (0, 7.5, 27.5 or 47.5 mg/g casein). Percent mortality was lower in rats fed diets without PABA than in those fed diets containing PABA. All further experiments were conducted without supplemental PABA. While the mean day of death was greater in the groups fed 12% casein, percent mortality in these groups was nearly twofold higher than in the groups fed 20% casein. The presence or absence of 15 mg methionine per gram casein had no effect on percent mortality, mean day of death, or percent parasitemia, regardless of dietary casein level. Supplementation of threonine at any level to the 12% casein diet with supplemental methionine resulted in mortality rates similar to those from animals fed the 20% casein diets, but percent mortality was not altered by threonine in the absence of supplemental methionine. The mean day of death of animals fed 20% casein increased with increments of added threonine. Methionine had no influence on this phenomenon. It is concluded that the quantity of dietary protein and the quality of its amino acid composition can have profound effects on the susceptibility of mice to malaria.

4-Aminobenzoic Acid↗
PubMed1984

25-Hydroxycholesterol-induced elevation in 45Ca uptake: correlation with depressed DNA synthesis.

The mechanism whereby 25-hydroxycholesterol, an inhibitor of the synthesis of cholesterol, depresses DNA synthesis in cycling P815 mastocytoma cells was investigated. The uptake of 45Ca into P815 cells treated with 1 microgram/ml 25-hydroxycholesterol began to rise above control levels by 6 hours after initiation of treatment and was increased tenfold by 15 hours. Kinetic data of calcium uptake indicated the presence of at least two components of calcium uptake, fast and slow. The fast phase of calcium exchange at the cell surface was changed little by treatment with 25-hydroxycholesterol. The slow phase of calcium exchange with the intracellular compartment was markedly affected by treatment with the inhibitor, there being a large increase in the flux and half-time of uptake, and a fall in the rate constant. This resulted in a large elevation of the intracellular compartment size. Incorporation of [3H]thymidine into DNA began to decline between 9 and 12 hours posttreatment in these cultures. Uptake of calcium and depression of DNA synthesis were shown to be directly related to the dose of 25-hydroxycholesterol used. The changes in 45Ca uptake and DNA synthesis due to 25-hydroxycholesterol treatment were abolished by addition of exogenous cholesterol to the incubation medium. The results are consistent with the hypothesis that 25-hydroxycholesterol, by inhibiting cholesterol production, depresses DNA synthesis via an elevation in the uptake of calcium into the cell to a level incompatible with continued DNA replication.

Animals↗
PubMed1984

Humoral immunity in essential fatty acid-deficient rats and mice: effect of route of injection of antigen.

Weanling male Lewis Mai F rats and A/J mice were fed semi-purified diets either adequate or deficient in essential fatty acids (EFA) for 50-60 days. After death livers were excised, the lipids were extracted, and the fatty acid profile was determined. Groups of rats and mice were immunized by injection with sheep red blood cells (sRBC) either i.v. or i.p. One group of rats received an injection of sRBC plus Bordetella pertussis organisms. The plaque-forming cell response (PFC) of all groups was determined. Samples of mouse spleens were analyzed for prostaglandin F2 alpha. EFA-deficient rat and mice liver fatty acid profiles showed elevated levels of omega 7 and omega 9 fatty acids and decreased omega 6 fatty acids. The fatty acid profiles of mice differed quantitatively from the rats. As determined by the ratios of 18:0 to 18:2 omega 6 and 18:2 omega 6 to 20:4 omega 6 mice showed a higher delta 9 and a lower delta 6 desaturase activity. When the antigen was injected i.v. the EFA-deficient animals of both species showed an increased PFC response compared to controls, but when it was injected i.p. there was no difference between dietary groups. The PFC response in rats receiving B. pertussis increased dramatically but the difference between dietary groups was abrogated. As had been previously shown in rats the increase in PFC response in the mice immunized by the i.v. route correlated with a decreased synthesis of PGF2 alpha by the spleen.

Animals↗
PubMed1983

Essential fatty acid deficiency, prostaglandin synthesis and humoral immunity in Lewis rats.

Essential fatty acid (EFA) deficiency is known to alter the immune response in several experimental systems. To further evaluate the effects of EFAs on immunity Lewis rats were fed diets either adequate or deficient in EFAs for 70-80 days. EFA-adequate rats responded to an i.v. injection of 5 X 10(8) sheep erythrocytes with a sharp, short-lived rise in splenic levels of PGE and PGF within 2 minutes after injection. EFA deficiency resulted in a diminution of this PG response. PG production in liver homogenates was also depressed in EFA-deficient liver. An i.v. injection of sheep erythrocytes resulted in a humoral response against this antigen, measured as hemolytic plaque-forming cells in the spleen. EFA deficiency, as well as pretreatment of EFA-adequate rats with indomethacin, an inhibitor of PG synthesis, resulted in a stimulation of the plaque-forming cell response over that observed in control, EFA-adequate rats. The alterations in immune response resulting from changes in PG synthetic capacity may be important in the etiology of certain immunodeficiency syndromes such as the lupus-erythematosus-like autoimmune disease in NZB/W mice.

Animals↗