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Biomedical subjects

E D Wills

Publications and source records attributed to E D Wills.

At least 19 recordsLinked to original sources
PubMed1987

The oxidation of benzo[a]pyrene-7,8-dihydrodiol mediated by lipid peroxidation in the rat intestine and the effect of dietary lipids.

This study has demonstrated that the microsomal fraction of the rat small intestinal mucosa has the capacity to catalyse the oxidation of benzo[a]pyrene(BP)-7,8-diol to BP-diol-epoxides (BPDEs) both by a mechanism involving the mixed-function oxidase system (NADPH-dependent) and as a result of the initiation of peroxidation of the membrane phospholipids by ferrous ions, ascorbate and ADP. The NADPH-dependent reaction was fastest in the proximal part of the intestine and resulted in the formation of approximately equal amounts of BPDE I and BPDE II. The lipid peroxidation-catalysed reaction favoured the production of BPDE I and was maximal in the middle region of the intestine, closely paralleling the rate of lipid peroxidation in the intestinal sections. Feeding rats on a cod liver oil diet, rich in C20:5 and C22:6, significantly increased the incorporation of these fatty acids into the microsomal fractions. This resulted in a greatly increased rate of lipid peroxidation in vitro and a significantly higher rate of lipid peroxidation-catalysed BP-7,8-diol oxidation compared to rats fed fat-free, mono-unsaturated lard or corn oil (58% C18:2) diets. Thus the rate of conversion of BP-7,8-diol to its ultimate carcinogenic forms during lipid peroxidation in the intestinal fractions of rats fed a polyunsaturated fat was quantitatively more important than the NADPH-catalysed reaction as measured in vitro.

Animals↗
PubMed1986

The effect of dietary lipids and antioxidants on the activity of epoxide hydratase in the rat liver and intestine.

The effect of varying the fatty acid composition of the lipid components of the diet on the activity of epoxide hydratase in the rat liver and intestinal mucosa has been studied. Feeding a 10% cod liver oil diet (containing 18% C20:5 and 11% C22:6) resulted in a 3-fold increase in epoxide hydratase activity in the liver and a 1.6-fold increase in the intestine compared to rats fed a fat-free diet. The activity of epoxide hydratase in rats fed a cod liver oil diet was significantly greater than that for the group fed a lard diet (containing mainly saturated and mono-unsaturated fatty acids) containing the same quantity of vitamin E. Thus, the enhancing effect of the cod liver oil diet was due to the polyunsaturated fatty acids in this oil. Dietary corn oil (58% C18:2) also stimulated epoxide hydratase activity in the liver but not in the intestine. Vitamin E levels of up to 500 mg/kg diet were ineffective at inducing epoxide hydratase activity in both the liver and intestine. Significant changes in the fatty acid composition of hepatic and intestinal microsomes took place when rats were fed diets of different fatty acid composition. These changes were such that the proportions of polyunsaturated fatty acids in the microsomal fractions reflected the amounts of these fatty acids in the dietary fat. Hepatic epoxide hydratase activity was found to be positively correlated to the proportion of polyunsaturated fatty acids in the microsomal fractions of the liver.

Animals↗
PubMed1986

The dependence of the rate of BP metabolism in the rat small intestinal mucosa on the composition of the dietary fat.

We studied the effects that dietary fat has on the capacity of preparations of rat small intestinal mucosal cells to metabolize benzo[a]pyrene (BP) in vitro and on the composition of fatty acids in the endoplasmic reticulum of the intestinal mucosa. When rats were fed diets containing different types of fat, there were significant changes in the incorporation of fatty acids into the endoplasmic reticulum of the mucosal cells of the small intestine: the proportions of polyunsaturated fatty acids in the endoplasmic reticulum reflected the amounts of these fatty acids in the dietary fat. The rate of BP oxidation in the intestinal mucosa was dependent on the amount and composition of the dietary fat, but the range and proportions of the metabolites produced were not affected. Dietary C18:2 was particularly important in elevating the rate of BP oxidation, but dietary C20:5 and C22:6 also effectively increased the rate of BP oxidation. The rate of BP oxidation in the small intestine of rats fed different diets was positively correlated with the proportion of polyunsaturated fatty acids in the endoplasmic reticulum of the mucosal cells.

Animals↗
PubMed1986

The oxidation of benzo[a]pyrene mediated by lipid peroxidation in irradiated synthetic diets.

The effect of gamma-irradiation (1000-4000 Gy) on the formation of lipid peroxides and on the oxidation of the environmental carcinogen benzo[a]pyrene (BP) has been studied in mixtures of starch/fat and BP which were used as models for natural foods. When mixtures containing polyunsaturated fats (mackerel oil and cod-liver oil which contain relatively large proportions of C20:5 and C22:6) were exposed to gamma-irradiation, large concentrations of lipid peroxide were formed and a concomitant oxidation of BP to mutagenic and toxic BP quinones took place. The rate of BP oxidation was closely related to the extent of peroxidation of the lipids in the starch mixtures and was dependent on the dose of gamma-irradiation and the presence of air. Mackerel oil also underwent peroxidation during the storage of both irradiated and unirradiated starch/mackerel oil/BP mixtures and this resulted in a significant oxidation of the BP present in these samples. Antioxidants such as vitamin E and BHA inhibited both lipid peroxidation and BP oxidation resulting from gamma-irradiation. These results demonstrate that the species generated during the peroxidation of unsaturated fats in foodstuffs can react with polycyclic aromatic hydrocarbons such as BP and convert them into active mutagenic and toxic products. This has important toxicological implications, particularly as the consumption of polyunsaturated fat in the Western world is increasing and gamma-irradiation may soon be widely used for food sterilization.

Benzo(a)pyrene↗
PubMed1984

The generation of oxidation products of benzo[a]pyrene by lipid peroxidation: a study using gamma-irradiation.

The role which active oxygen and radicals generated by the peroxidation of unsaturated fatty acids could play in the oxidation of benzo[a]pyrene has been studied using gamma-irradiation. Irradiation of benzo[a]pyrene resulted in the formation of benzo[a]pyrene 1,6-, 3,6- and 6,12-quinones and other more polar products which were analysed by h.p.l.c. OH. radicals are believed to be involved in this oxidation. The presence of polyunsaturated fatty acids and polyunsaturated lipids stimulated the formation of benzo[a]pyrene products following gamma-irradiation. Oxidation of benzo[a]pyrene also occurred over a period of days in the presence of autoxidising mackerel oil. The rate of benzo[a]pyrene oxidation was related to the extent of lipid peroxidation as determined by malonaldehyde formation. Malonaldehyde production as a result of peroxidising lipids was inhibited by benzo[a]pyrene which suggested that benzo[a]pyrene reacted directly with lipid peroxy radicals or hydroperoxides generated in the process of lipid peroxidation. These results demonstrate that oxidation products of the peroxidation of lipids and fatty acids are able to react directly with benzo[a]pyrene to form products including benzo[a]pyrene quinones without the presence of enzymes such as the cytochrome P-450 mixed function oxidase system and prostaglandin synthetase. It is possible that benzo[a]pyrene may be activated by these types of reactions in vivo or in vitro when benzo[a]pyrene is in contact with polyunsaturated lipids in foodstuffs or the intestinal lumen and peroxidation of unsaturated fats may play an important role in human carcinogenesis.

Antioxidants↗
PubMed1979

The distribution of glutathione in the rat liver lobule.

A quantitative cytochemical method was developed for measuring the GSH (reduced glutathione) content of hepatocytes in different regions of the rat liver lobule. Use of this method enabled us to show that GSH is not evenly distributed within the rat liver lobule. The hepatocytes located within 100 micrometer of the central vein contain much less GSH than do those in other regions of the rat liver lobule. We suggest that this partially explains the peculiar susceptibility of these cells to electrophilic attack by toxic metabolites formed via the microsomal cytochrome P-450 system.

Animals↗
PubMed1979

The effect of dietary fats on the composition of the liver endoplasmic reticulum and oxidative drug metabolsim.

1. The dependence of the rate of oxidative demethylation in the liver endoplasmic reticulum on the fatty acid composition of the endoplasmic reticulum has been studied by varying the lipid content of the diet. 2. The rate of oxidative demethylation was markedly dependent on the percentage of linoleic acid (18:2) incorporated into the membrane. Feeding diets containing (g/kg) 100 coconut oil, 100 lard or 100 maize oil caused respectively the incorporation of 7.6, 10.3 and 25.1% linoleic acid (18:2) and a demethylation rate 3.26, 3.15 and 5.03 nmol formaldehyde/min per mg protein. Feeding 100 g herring oil/kg diet caused incorporation of only 5.1% C18:2 but also 27.2% omega 3 unsaturated fatty acids, including 8.7% eicosapentaenoic acid (20:5) and 17.0% docosahexaenoic acid (22.6) and caused a very high rate of oxidative demethylation (6.53 nmol formaldehyde/min per mg protein). 3. Destruction of the polyunsaturated fatty acids in herring oil by irradiation with 400 krad caused incorporation of a smaller quantity of 3 omega unsaturated acids into the endoplasmic reticulum and decreased the rate of oxidative demethylation (4.83 nmol formaldehyde/min per mg protein). 4. The inductive effects of phenobarbitone on oxidative demethylation were partially dependent on changes in the fatty acid composition of the endoplasmic reticulum. Phenobarbitone (100 mg/kg) increased the percentage of C18:2 from 25.1 to 29.4% in rats given a maize-oil diet, increased the percentage of C20:5 from 8.7 to 10.3% in rats given a herring-oil diet and decreased the percentage of arachidonic acid (20:4) and C22.6 in rats given a lard, maize-oil, herring-oil or irradiated-herring-oil diet. 5. Intraperitoneal alpha-tocopherol (50 mg/kg) increased the percentage of C20:4 from 11.1 to 13.1% in rats given a lard diet and from 5.9 to 7.3% in rats given a herring-oil diet. 6. It is concluded that dietary C18:2 is an important factor in the regulation of the rate of oxidative demethylation in the liver endoplasmic reticulum but this may be replaced effectively by dietary C20:5 omega 3 and C22:6 omega 3 acids. Oxidative demethylation is regulated by changes in the fatty acid composition of the membranes of the liver endoplasmic reticulum.

Aminopyrine↗
PubMed1979

The effect of ionizing radiation on the fatty acid composition of natural fats and on lipid peroxide formation.

The effects of irradiation doses of 200-1000 krad on the fatty acid compositions of saturated and unsaturated natural food fats have been studied. Lard, coconut oil, corn oil, methyl linoleate and herring oil have been analysed before and after irradiation for lipid peroxide content and fatty acid composition. The effects of storage under varied conditions after irradiation have also been investigated. Irradiation doses of 200-1000 krad had little effect on the fatty acid compositions of saturated fats (lard and coconut oil) or of fats with a high antioxidant content (corn oil) but caused destruction of 98 per cent of the highly unsaturated acids (18: 4,20 :5,22 : 6) and 46 per cent of the diene acids (18:2) in herring oil. The destruction of the polyunsaturated fatty acids increased with increasing storage temperature and storage time. The destruction of polyunsaturated fatty acids is accompanied by an increase in lipid peroxide formation. It is considered that changes in fatty acid composition in natural foods after irradiation are important in consideration of the use of irradiation for food preservation.

Fats↗
PubMed1978

The role of lipid components of the diet in the regulation of the fatty acid composition of the rat liver endoplasmic reticulum and lipid peroxidation.

The fatty acid compositions of the lipids and the lipid peroxide concentrations and rates of lipid peroxidation were determined in suspensions of liver endoplasmic reticulum isolated from rats fed on synthetic diets in which the fatty acid composition had been varied but the remaining constituents (protein, carbohydrate, vitamins and minerals) kept constant. Stock diet and synthetic diets containing no fat, 10% corn oil, herring oil, coconut oil or lard were used. The fatty acid composition of the liver endoplasmic reticulum lipid was markedly dependent on the fatty acid composition of the dietary lipid. Feeding a herring-oil diet caused incorporation of 8.7% eicosapentaenoic acid (C(20:5)) and 17% docosahexaenoic acid (C(22:6)), but only 5.1% linoleic acid (C(18:2)) and 6.4% arachidonic acid (C(20:4)), feeding a corn-oil diet caused incorporation of 25.1% C(18:2), 17.8% C(20:4) and 2.5% C(22:6) fatty acids, and feeding a lard diet caused incorporation of 10.3% C(18:2), 13.5% C(20:4) and 4.3% C(22:6) fatty acids into the liver endoplasmic-reticulum lipids. Phenobarbitone injection (100mg/kg) decreased the incorporation of C(20:4) and C(22:6) fatty acids into the liver endoplasmic reticulum of rats fed on a lard, corn-oil or herring-oil diet. Microsomal lipid peroxide concentrations and rates of peroxidation in the presence of ascorbate depended on the nature and quantity of the polyunsaturated fatty acids in the diet. The lipid peroxide content was 1.82+/-0.30nmol of malonaldehyde/mg of protein and the rate of peroxidation was 0.60+/-0.08nmol of malonaldehyde/min per mg of protein after feeding a fat-free diet, and the values were increased to 20.80nmol of malonaldehyde/mg of protein and 3.73nmol of malonaldehyde/min per mg of protein after feeding a 10% herring-oil diet in which polyunsaturated fatty acids formed 24% of the total fatty acids. Addition of alpha-tocopherol to the diets (120mg/kg of diet) caused a very large decrease in the lipid peroxide concentration and rate of lipid peroxidation in the endoplasmic reticulum, but addition of the synthetic anti-oxidant 2,6-di-t-butyl-4-methylphenol to the diet (100mg/kg of diet) was ineffective. Treatment of the animals with phenobarbitone (1mg/ml of drinking water) caused a sharp fall in the rate of lipid peroxidation. It is concluded that the polyunsaturated fatty acid composition of the diet regulates the fatty acid composition of the liver endoplasmic reticulum, and this in turn is an important factor controlling the rate and extent of lipid peroxidation in vitro and possibly in vivo.

Animals↗