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Biomedical subjects

J R Arthur

Publications and source records attributed to J R Arthur.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effects of smoking and vitamin E on blood antioxidant status.

Despite similar vitamin E contents, erythrocytes of smokers have an increased tendency (P less than 0.01) to peroxidize in vitro compared with those of nonsmokers. This difference is abolished by vitamin E supplementation (1000 mg alpha-tocopherol acetate/d for 14 d). The increased susceptibility to erythrocyte peroxidation in the smokers may reflect lower glucose-6-phosphate dehydrogenase (P less than 0.02) and glutathione peroxidase (P less than 0.05) activities. Smokers seem to be under a sustained oxidant stress with increased plasma-conjugated dienes (P less than 0.01) and dehydroascorbate (P less than 0.05) and decreased ascorbate (P less than 0.06) concentrations. Additionally, plasma ceruloplasmin in smokers is elevated (P less than 0.01), consistent with an acute-stress response. Plasma total cholesterol is similar in smokers and nonsmokers and is unaffected by vitamin E supplementation. Indices of sustained oxidant stress in smokers are partially ameliorated by vitamin E supplementation.

Adult↗
PubMed1991

Impairment of iodothyronine 5'-deiodinase activity in brown adipose tissue and its acute stimulation by cold in selenium deficiency.

The activity of the type II iodothyronine 5'-deiodinase enzyme in brown adipose tissue has been examined in rats-fed a selenium-deficient diet. Iodothyronine 5'-deiodinase activity was threefold lower in brown adipose tissue of deficient rats than in control animals. The activity of glutathione peroxidase, a biochemical index of selenium deficiency, was also greatly decreased in deficient animals. Cytochrome oxidase activity in brown fat was, however, unaltered by selenium deficiency. Acute exposure to cold (4 degrees C for 18 h) resulted in a substantial increase in iodothyronine 5'-deiodinase activity in brown adipose tissue of control rats, but the stimulatory effect of cold was attenuated in selenium-deficient animals. These results support the concept that the iodothyronine 5'-deiodinases are selenium-dependent enzymes, and indicate that the thermogenic response to cold may be impaired in selenium deficiency.

Adipose Tissue↗
PubMed1991

The role of selenium in thyroid hormone metabolism.

In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical changes caused by selenium deficiency. Recently, however, type I iodothyronine 5'-deiodinase has also been shown to be a selenium-containing enzyme. This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with a normal vitamin E status. Since iodothyronine 5'-deiodinases are essential for the production of the active thyroid hormone 3,5,3'-triiodothyronine, some of the consequences of selenium deficiency may result from thyroid changes rather than inability to metabolise peroxides. In particular, the impaired thyroid hormone metabolism may be responsible for decreased growth and resistance to cold stress in selenium-deficient animals. A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency. Selenium status may therefore have a major influence on the outcome of iodine deficiency in both human and animal populations.

Animals↗
PubMed1991

Inhibitory effects of isomers of tocopherol on lipid peroxidation of microsomes from vitamin E-deficient rats.

NADPH-induced lipid peroxidation of hepatic microsomes from vitamin E-deficient rats has been used to assess the antioxidant effectiveness of dl alpha, d alpha- and gamma-tocopherol. When the tocopherols were added in ethanol to microsomes, the degree of inhibition of formation of thiobarbituric acid reactive substances (TBARS) decreased in the order dl alpha- greater than d alpha- greater than gamma-tocopherol. This reflected the difference in the solubility of the tocopherols in the microsomes, dl alpha-tocopherol being the most soluble and gamma-tocopherol the least. Using inhibition of TBARS produced per tocopherol content in microsome as a measure of antioxidant potency, the effectiveness of the isomers was gamma- greater than d alpha- greater than dl alpha. Despite addition of pharmacological concentrations of the isomers, it was not possible to inhibit lipid peroxidation to the same levels as were found in microsomes from vitamin E sufficient animals. Use of ethanol as a vehicle may not allow optimum orientation of the tocopherols into the lipid bilayer.

Animals↗
PubMed1991

Dietary vitamin E decreases ESR signal intensity in hepatic microsomal preparations from malignant hyperthermia susceptible pigs.

On incubation with the spin trap alpha-(4-pyridyl-l-oxide)-N-tert-butylnitrone (4-POBN), a characteristic electron spin resonance (ESR) signal was produced at a greater rate in hepatic microsomal fractions from malignant hyprthermia susceptible (MHS) pigs compared with resistant (MHR) pigs. This was accompanied by increased formation of thiobarbituric acid reactive substances (TBARS). Supplementation of diets for six weeks with 235 mg alpha-tocopherol acetate/kg significantly increased microsomal vitamin E content of both pigs types. Moreover, the rate of formation of TBARS and ESR signal height of incubated microsomes from supplemented MHS pigs was decreased to that of MHR pigs. Elevated pyruvate kinase activities and TBARS concentrations in plasma of MHS pigs were also moderated by dietary vitamin E. Vitamin E supplementation may decrease the peroxidative events associated with MH.

Animals↗
PubMed1991

Inter-relationships between selenium and thyroid hormone metabolism in the rat and man.

Labelling of rat kidney microsomes in vitro with [125I]-bromoacetyl T4 produced two bands on SDS/PAGE with Mr of 55 kDa and 27.5 kDa representing protein disulphide isomerase and type I iodothyronine deiodinase (ID-I) respectively. The amount of the 55 kDa band was unchanged by selenium (Se) deficiency but the 27.5 kDa protein was markedly decreased in kidney microsomal fraction obtained from Se-deficient rats. Concurrent Se and iodine deficiency produced a significant increase in thyroid weight, plasma thyrotrophin (TSH) and a decrease in thyroidal iodine when compared with either single Se or iodine deficiency. These results suggest that ID-I is a selenoprotein and that Se deficiency can exacerbate the hypothyroidism observed in iodine deficiency. In man, blood glutathione peroxidase and blood Se levels were decreased in hyperthyroidism due to Graves' disease whilst normal levels of these analytes were found in patients treated for Graves' disease. These results suggest that thyroid status can affect Se balance rather than Se deficiency predisposes to Graves' disease.

Animals↗
PubMed1990

Hepatic iodothyronine 5'-deiodinase. The role of selenium.

Selenium (Se) deficiency decreased by 8-fold the activity of type 1 iodothyronine 5'-deiodinase (ID-I) in hepatic microsomal fractions from rats. Solubilized hepatic microsomes from rats injected with 75Se-labelled Na2SeO3 4 days before killing were found by chromatography on agarose gels to contain a 75Se-containing fraction with ID-I activity. PAGE of this fraction under reducing conditions, followed by autoradiography, revealed a single 75Se-containing protein (Mr 27,400 +/- 300). This protein could also be labelled with 125I-bromoacetyl reverse tri-iodothyronine, an affinity label for ID-I. The results suggest that hepatic ID-I is a selenoprotein or has an Se-containing subunit essential for activity.

Animals↗
PubMed1990

The changes in hepatic enzyme expression caused by selenium deficiency and hypothyroidism in rats are produced by independent mechanisms.

Selenium (Se) deficiency for 5 weeks in rats produced changes in the activity of a number of hepatic, renal and plasma enzymes. In animals whose food intake was restricted to 75% of normal for 2 weeks, Se deficiency produced significant increases in the activity of hepatic cytosolic 'malic' enzyme and mitochondrial alpha-glycerophosphate dehydrogenase (GPD), two enzymes that are particular sensitive to the thyroid-hormone concentrations in tissue. Propylthiouracil-induced hypothyroidism produced significant decreases in 'malic' enzyme and GPD activities. The effect of hypothyroidism on the activity of 'malic' enzyme, GPD and other enzymes studied in liver and plasma was often opposite to that seen in Se deficiency. Glutathione S-transferase (GST) activity was increased by both Se deficiency and hypothyroidism, but in hypothyroid animals further significant increases in GST were produced by Se deficiency. These data suggest that the changes in enzyme expression observed in Se deficiency are not caused by decreased tissue exposure to thyroid hormones.

Animals↗
PubMed1990

The effects of selenium depletion and repletion on the metabolism of thyroid hormones in the rat.

Rats were fed selenium-deficient (less than 0.005 mg selenium/kg) or selenium-supplemented diets (0.1 mg selenium/kg, as Na2SeO2) for up to five wks from weaning to assess the effects of developing selenium deficiency on the metabolism of thyroid hormones. Within two wks 3:5,3'-triiodothyronine (T3) production from thyroxine (T4) in liver homogenates from selenium-deficient rats was significantly lower compared with the activity in liver homogenates from selenium-supplemented rats. This decreased activity was probably responsible, in part, for the higher T4 and lower T3 concentrations in plasma from the selenium-deficient rats after 3, 4, and 5 weeks of experiment. Repletion of selenium-deficient rats with single intra-peritoneal injections of 200 micrograms selenium/kg body wt. (as Na2SeO3) 5 days before sampling reversed the effects of the deficiency on thyroid hormone metabolism and significantly increased liver and plasma glutathione peroxidase activities. However a dose of 10 micrograms selenium/kg body wt given to rats of similar low selenium status had no effect on thyroid hormone metabolism or glutathione peroxidase activity but did reverse the increase in hepatic glutathione S-transferase activity characteristic of severe selenium deficiency. Imbalances in thyroid hormone metabolism are an early consequence of selenium deficiency and are probably not related to changes in hepatic xenobiotic metabolizing enzymes associated with severe deficiency.

Animals↗
PubMed1990

Spin trapping of free radicals and lipid peroxidation in microsomal preparations from malignant hyperthermia susceptible pigs.

Microsomes were prepared from livers of malignant hyperthermia susceptible (MHS) or resistant (MHR) pigs. On incubation with the spin trap alpha-(4-pyridyl-l-oxide)-N-tert-butylnitrone (4-POBN), the microsomes from MHS pigs produced a characteristic electron spin resonance (ESR) signal at a greater rate than those from MHR pigs. Increased formation in the incubations of thiobarbituric acid reactive substances (TBARS) by the microsomes of the MHS pigs indicated an enhanced susceptibility to free radical-mediated lipid peroxidation. These results provide further evidence that MHS pigs have an antioxidant abnormality which may contribute to the fatal MH response. However the nature of the abnormality is unclear. The enhanced formation of unstable free radicals and indices of lipid peroxidation was not due to decreased vitamin E concentration or glutathione peroxidase activity in the microsomes. Furthermore, fatty acid profiles were similar in microsomes from MHS and MHR pigs indicating similar amounts of potential substrate for TBARS formation.

Animals↗
PubMed1990

Anaemia and changes in erythrocyte morphology associated with copper and selenium deficiencies and dietary restriction in rats.

Both selenium and copper deficiencies in rats caused morphological changes in erythrocytes but only copper deficiency resulted in anaemia. Similar but less severe morphological changes occurred when rats consuming selenium- and copper-adequate diets had their food intake restricted to that of the copper-deficient animals. Since selenium deficiency did not affect the severity of changes due to copper deficiency this suggests that alterations of erythrocyte morphology may not be entirely due to impaired functions of selenium and copper in cell antioxidant systems. Thus, erythrocyte structure was sensitive to several dietary changes and such alterations are probably independent of the anaemia induced by copper deficiency. This possibility should be considered when changes in erythrocyte morphology are attributed to copper or selenium deficiency in animals which also have a restricted food intake.

Anemia↗
PubMed1989

Increased indices of lipid peroxidation in stress-susceptible pigs and effects of vitamin E.

When stress-susceptible and stress-resistant pigs consumed diets containing 10 iu vitamin E kg-1, the stress-susceptible pigs had damaged cell membranes. This was indicated by increased plasma activities of creatine kinase and pyruvate kinase. Plasma concentrations of thiobarbituric acid reactive substances and conjugated dienes were also increased suggesting that the membrane damage was caused by free radicals. Susceptibility to free radicals was further demonstrated by an increased tendency for erythrocytes and tissue homogenates from stress-susceptible pigs to peroxidise when incubated with hydrogen peroxide and iron, respectively. Supplementation of the diets with approximately 20 times normal requirements of vitamin E decreased plasma creatine kinase and pyruvate kinase activities, and inhibited the formation of the indices of peroxidation in vivo and in vitro. It is concluded that the stress-susceptible pig has an abnormality in its antioxidant defence mechanisms. However, this abnormality was not due to a deficiency in selenium-dependent glutathione peroxidase, since activities were significantly increased in the longissimus dorsi of stress-susceptible pigs. Although the nature of the antioxidant defect is unclear, it is suggested that stress-susceptible pigs are under a sustained oxidant stress and that a decreased ability to accommodate even a normal free radical load may contribute to the rapid development of the fatal stress response.

Animals↗
PubMed1989

Increased peroxidation of erythrocytes of stress-susceptible pigs: an improved diagnostic test for porcine stress syndrome.

When incubated with solutions of hydrogen peroxide, erythrocytes of stress-susceptible pigs produced more by-products of lipid peroxidation (as measured as thiobarbituric acid-reactive substances [TBARS]) than did erythrocytes from stress-resistant pigs. Using this technique, discrimination between the 2 pig types was absolute at hydrogen peroxide concentrations of 0.9 and 1.5%. This was in contrast to other methods of identifying stress-susceptible pigs, such as osmotically induced erythrocyte lysis and the determination of plasma pyruvate kinase and creatine kinase activities, for which considerable overlap of data was observed between pig types. The increased TBARS production by erythrocytes was further evidence for the existence of an antioxidant abnormality in stress-susceptible pigs. However, because there were no discernible differences in the major blood antioxidant-related values between stress-susceptible and stress-resistant pigs, the nature of the defect remains unclear. The production of TBARS by erythrocytes when incubated with hydrogen peroxide provides an improved method for identifying stress-susceptible pigs.

Animals↗
PubMed1988

Effects of selenium and vitamin E status on plasma creatine kinase activity in calves.

In four experiments, attempts were made to induce nutritional myopathy in calves given a selenium- and vitamin E-deficient diet (less than 0.01 mg Se/kg, less than 2 mg total vitamin E/kg). In housed calves, combined selenium and vitamin E deficiency was insufficient to provoke the large increase in plasma creatine kinase activity typical of muscle damage. Such increases were only obtained when selenium- and vitamin E-deficient calves were turned out from indoor housing in small pens to open pasture. The rises in plasma creatine kinase activity on turnout were prevented when the calves had consumed diets supplemented with 0.1 mg Se/kg (as Na2SeO3). The percentage of the polyunsaturated fatty acid, linolenic acid (18:3 omega 3), in plasma total fatty acids was up to 10-fold higher in calves consuming fresh grass at pasture or indoors than in those housed indoors and fed purified diet. However, in the housed calves there were no rises in plasma creatine kinase activity, whereas large increases occurred in those turned out to pasture. Thus, because increased dietary polyunsaturated fatty acid at turnout is not the sole trigger for the development of myopathy in selenium- and vitamin E-deficient calves, additional unidentified dietary or environmental factors must also be involved.

Animals↗
PubMed1988

Spin trapping of free radicals in homogenates of heart from selenium and vitamin E deficient rats.

The formation of unstable free radical species in homogenates of heart from selenium and/or vitamin E deficient rats has been investigated by electron spin resonance spectroscopy using the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. There was only a small amount of free radical formation by heart from control or selenium deficient animals. However, the amounts and rates of formation of free radicals were significantly higher in animals with vitamin E deficiency and higher still in those with combined selenium and vitamin E deficiency.

Animals↗