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Biomedical subjects

J R Arthur

Publications and source records attributed to J R Arthur.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protection conferred by selenium deficiency against aflatoxin B1 in the rat is associated with the hepatic expression of an aldo-keto reductase and a glutathione S-transferase subunit that metabolize the mycotoxin.

Fischer 344 rats fed on a diet that is deficient in selenium are more resistant to the hepatocarcinogen aflatoxin B1 (AFB1) than those fed on a selenium-sufficient diet. Hepatic cytosol from either selenium-deficient Fischer 344 rats or Hooded Lister rats possesses a marked increase in both reductase activity toward AFB1-dialdehyde and glutathione S-transferase (GST) activity toward AFB(1)-8,9-epoxide than hepatic cytosol from selenium-sufficient rats. The elevation in hepatic AFB1-aldehyde reductase (AFAR) activity in selenium-deficient animals is accompanied by an increase of 11- and 15-fold in the levels of AFAR protein in liver cytosol from Fischer 344 and Hooded Lister rats, respectively. The amount of AFAR protein in selenium-sufficient and -deficient Fischer rats was modulated by treatment with N-acetylcysteine; this antioxidant reduced basal expression of AFAR but did not modulate the relative overexpression of AFAR during selenium deficiency. The enhanced capacity to conjugate glutathione with AFB(1)-8,9-epoxide in selenium-deficient livers from Fischer 344 and Hooded Lister rats is associated with a 5- and 7-fold increase, respectively, in the hepatic levels of the AFB1-metabolizing alpha-class GSTA5 subunit. The elevated levels of AFAR and GSTA5 protein in the selenium-deficient animals coincided with increases in the steady-state levels of their mRNAs. In selenium-deficient Fischer 344 rats, AFAR and GSTA5 were both found to be expressed throughout the centrilobular and midzonal areas of the liver lobule but were essentially absent from periportal hepatocytes. The effect of selenium insufficiency is pleiotropic, and it was also noted that the theta-class GSTT1 is overexpressed 3- and 10-fold in livers of selenium-deficient Hooded Lister and Fischer 344 rats. Inasmuch as GSTT1 is responsible for the metabolic activation of dihaloalkanes, selenium deficiency may increase the susceptibility of rats to mutagens such as dichloromethane.

Acetylcysteine↗
PubMed1997

Selenium status of a group of Scottish adults.

OBJECTIVE: To examine dietary selenium intake and indices of selenium status (plasma and red blood cell selenium and glutathione peroxidase activities) in apparently healthy Scottish individuals. DESIGN AND SUBJECTS: One hundred subjects, aged between 40 and 60 y, completed a seven day weighed food intake and provided blood samples for selenium status analysis. SETTING: Inverurie, Aberdeenshire, Scotland. RESULTS: Average reported selenium intake was low (43 micrograms/d). A significant number of subjects had reported intakes below the RNI. Low levels of plasma selenium were also found but no subject had values below 40 micrograms/1. Red blood cell selenium was within the reference range established for a healthy UK population. Smoking status had no consistent effect on selenium status. CONCLUSIONS: The results of the present study suggest that selenium status of certain Scottish individuals may be compromised and that further studies are warranted. SPONSORSHIP: BASF, Germany; The Tobacco Products Research Trust, UK; Scottish Office Agriculture Environment and Fisheries Department.

Adult↗
PubMed1997

Selenium and iodine deficiencies: effects on brain and brown adipose tissue selenoenzyme activity and expression.

Adequate dietary iodine supplies and thyroid hormones are needed for the development of the central nervous system (CNS) and brown adipose tissue (BAT) function. Decreases in plasma thyroxine (T4) concentrations may increase the requirement for the selenoenzymes types I and II iodothyronine deiodinase (ID-I and ID-II) in the brain and ID-II in BAT to protect against any fall in intracellular 3,3',5 tri-iodothyronine (T3) concentrations in these organs. We have therefore investigated selenoenzyme activity and expression and some developmental markers in brain and BAT of second generation selenium- and iodine-deficient rats. Despite substantial alterations in plasma thyroid hormone concentrations and thyroidal and hepatic selenoprotein expression in selenium and iodine deficiencies, ID-I, cytosolic glutathione peroxidase (cGSHPx) and phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activities and expression remained relatively constant in most brain regions studied. Additionally, brain and pituitary ID-II activities were increased in iodine deficiency regardless of selenium status. This can help maintain tissue T3 concentrations in hypothyroidism. Consistent with this, no significant effects of iodine or selenium deficiency on the development of the brain were observed, as assessed by the activities of marker enzymes. In contrast, BAT from selenium- and iodine deficient rats had impaired thyroid hormone metabolism and less uncoupling protein than in tissue from selenium- and iodine-supplemented animals. Thus, the effects of selenium and iodine deficiency on the brain are limited due to the activation of the compensatory mechanisms but these mechanisms are less effective in BAT.

Adipose Tissue, Brown↗
PubMed1997

Selenium and iodine deficiencies and selenoprotein function.

This paper reviews some recent findings on the interactions between selenium deficiency and iodine deficiency. Both micronutrients can control the levels of selenoprotein mRNAs, particularly in the thyroid and brain. When selenium and iodine supplies are limiting the compensatory mechanisms work to minimise adverse effects on thyroid hormone metabolism and thus neurological development. The mechanisms for regulation of selenoproteins in selenium and iodine deficiency are however very tissue-specific. For example, unlike the brain and thyroid, brown adipose tissue is unable to retain selenoproteins in selenium and iodine deficiency and is therefore at greater risk from injurious effects of the deficiencies.

Animals↗
PubMed1996

Role of the 3' untranslated region in the regulation of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression by selenium supply.

Selenium is an essential nutrient and synthesis of selenoproteins is affected by limited selenium supply. During selenium deficiency there is a differential regulation of selenoprotein synthesis and gene expression; for example, there is a decrease in abundance of mRNA for cytosolic glutathione peroxidase (cGSH-Px) and a preservation of mRNA for phospholipid-hydroperoxide glutathione peroxidase (PHGSH-Px). This difference is not due to an alteration in the rate of transcription but might reflect differences in translation. The aim of the present work was to assess the role of cGSH-Px and PHGSH-Px 3' untranslated regions (UTRs) in the regulation of selenoprotein mRNA stability and translation by using H4-II-E-C3 cells transfected with different constructs containing a type I iodothyronine deiodinase-coding region linked to different selenoprotein mRNA 3' UTRs. Translational efficiency results showed that the efficiency of the 3' UTRs in permitting selenocysteine incorporation is similar in selenium-replete conditions but, when selenium is limiting, the 3' UTR of cGSH-Px is less efficient than the 3' UTR of PHGSH-Px. The results suggest that the 3' UTR of these selenoprotein mRNA species influences their extent of translation when selenium levels are low. The different sensitivity of the 3' UTRs to selenium deficiency can explain the differential effect that selenium deficiency has on cGSH-Px and PHGSH-Px activity and mRNA levels, stability and translation. This might be partly responsible for channelling selenium for synthesis of PHGSH-Px rather than cGSH-Px.

Animals↗
PubMed1996

Selective control of cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNA stability by selenium supply.

Selenium depletion of H4 hepatoma cells reduced cytosolic glutathione peroxidase (cGSH-Px) mRNA abundance but had no effect on phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px) mRNA abundance. Actinomycin D chase experiments showed that selenium depletion had no effect on the stability of PHGSH-Px mRNA but decreased the stability of cGSH-Px mRNA. In Se-replete cells puromycin decreased the stability of both cGSH-Px and PHGSH-Px mRNAs. The results suggest that when selenium supply is limiting PHGSH-Px mRNA translation is maintained more than that of cGSH-Px mRNA, and thus more cGSH-Px mRNA is released from polysomes and degraded.

Animals↗
PubMed1996

Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus.

BACKGROUND: We investigated an outbreak of acute clinical illness among 19 people who ate raw fish (sashimi) prepared from the white sucker, Catostomus commersoni, caught in a river north of Montreal, Canada. METHODS: We collected epidemiological, clinical, laboratory, and serological data on 19 individuals who ate the sashimi and six who did not. Because of the suggestive clinical picture, we set out to recover helminth parasites from uneaten fish. FINDINGS: The illness consisted of persistent upper abdominal pain, low grade fever, high blood eosinophil concentrations, and raised liver enzymes. After 10 days, opisthorchild-like eggs were found in stools. Symptoms persisted for 3 days to 4 weeks without treatment, but responded rapidly to praziquantel therapy. Necropsy of golden hamsters infected with metacercariae from uneaten fish revealed adult flukes identified as Metorchis conjunctus. INTERPRETATION: We describe an acute illness caused by the North American liver fluke M conjunctus. This is a new human disease and is the first report of a common-source outbreak of an acute illness caused by liver flukes of the family Opisthorchiidae.

Adult↗
PubMed1996

Selenoprotein gene expression during selenium-repletion of selenium-deficient rats.

Selenium repletion of selenium-deficient rats with 20 micrograms selenium / kg body weight as Na2SeO3 was used as a model to investigate the mechanisms that control the distribution of the trace element to specific selenoproteins in liver and thyroid. Cytosolic glutathione peroxidase (cGSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGSHPx), and iodothyronine 5'-deiodinase (IDI) activities were all transiently increased in liver 16 to 32 h after ip injection with selenium. However, only cGSHPx and PHGSHPx activities increased in the thyroid where IDI activity was already increased by selenium deficiency. These responses were owing to synthesis of the seleoproteins on newly synthesised and/or existing mRNAs. The selenoprotein mRNAs in the thyroid gland were increased two- and threefold after the transitory increases in selenoprotein activity. In contrast, there were parallel changes in selenoprotein mRNAs and enzyme activities in the liver, with no prolonged rises in mRNA levels. The organ differences suggest that increased thryotrophin (TSH) concentrations, which are known to induce thyrodial IDI and mRNA, may control the mRNAs for all the thyroidal selenoproteins investigated and be a major mechanism for the preservation of thyroidal selenoproteins when selenium supplies are limited.

Animals↗
PubMed1996

Effects of vitamin E supplementation on erythrocyte antioxidant defence mechanisms of smoking and non-smoking men.

1. During all aerobic metabolism, free radicals generated by the partial reduction of oxygen are potentially injurious to cells. Highly efficient antioxidant defence systems exist to inhibit oxidative damage to cellular lipids and proteins. Specific enzymes have a crucial role in these antioxidant defences, and their activity may be induced by regulatory mechanisms that respond to oxygen metabolite concentration. 2. To assess whether smoking induces an additional adaptive response, we compared antioxidant defence systems in erythrocytes from smokers and non-smokers and assessed whether a high intake of vitamin E (280 mg/day), a major lipophilic free-radical-scavenging antioxidant, affects the activity of antioxidant enzymes. 3. A total of 100 men, 50 smokers and 50 non-smokers, were allocated to four treatment groups in a 2 x 2 factorial design (smokers versus non-smokers and placebo versus vitamin E). For 10 weeks each subject took one capsule per day of either 280 mg dl-alpha-tocopherol acetate or a visually identical placebo (hydrogenated coconut oil with negligible vitamin E content). 4. Despite increased erythrocyte cytosolic antioxidant enzyme activities in smokers compared with non-smokers, erythrocytes from smokers were more susceptible to hydrogen peroxide-induced lipid peroxidation in vitro. 5. Vitamin E supplementation further increased erythrocyte catalase (EC 1.11.1.6) activity in both smokers and non-smokers (P < 0.001) and erythrocyte glutathione peroxidase (EC 1.11.1.9) and glutathione reductase (EC 1.6.4.2) activities in non-smokers (P < 0.001). After supplementation with vitamin E there was a concomitant fall in erythrocyte superoxide dismutase (EC 1.15.1.1) activity (P < 0.001) and total glutathione concentration (P < 0.01). Furthermore, in both smokers and non-smokers there was a significant decrease in the susceptibility of erythrocytes to peroxidation (P < 0.001). 6. Various endogenous and exogenous factors exert control over cellular protection against reactive oxygen species, and our data suggest that one such factor is the supply of vitamin E.

Antioxidants↗
PubMed1996

Selenoenzyme expression in thyroid and liver of second generation selenium- and iodine-deficient rats.

The stimulation of thyroid hormone synthesis in iodine deficiency may increase the requirement for the selenoproteins which are involved in thyroid hormone synthesis in the thyroid gland. Selenoenzyme activity and expression were investigated in the thyroid and liver of second generation selenium-and/or iodine-deficient rats. Selenium deficiency caused substantial decreases in hepatic selenium-containing type I iodothyronine deiodinase (ID-I) and cytosolic glutathione peroxidase (cGSHPx) activities and mRNA abundances, but phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activity was only 55% of selenium-supplemented control levels, despite the absence of change in its mRNA abundance. Selenoenzyme mRNA concentrations were maintained at control levels in thyroid glands from the selenium-deficient rat pups. Despite this, a differential effect was observed in selenoenzyme activities: ID-I activity was decreased to 61%, cGSHPx activity to 45% and phGSHPx to 29% of that in selenium-adequate controls. In iodine-deficient thyroid glands, mRNA levels were increased 2.2, 5.0 and 2.8 times for ID-I, cGSHPx and phGSHPx respectively. ID-I and cGSHPx enzyme activities were also increased but the activity of phGSHPx was decreased despite the high mRNA abundance. Thyroid selenoprotein mRNA levels were also increased in combined selenium and iodine deficiency but again there were differential effects on enzyme activities, with ID-I activity increased, cGSHPx unchanged and phGSHPx decreased. Thus, iodine deficiency may produce an oxidant stress on the thyroid gland, increasing the requirement for selenium to maintain selenoenzyme activity. When dietary supplies of selenium are limiting, thyroid selenoprotein mRNA levels are increased to compensate for overall lack of the micronutrient. Furthermore, there is a preferential supply of available selenium to ID-I and cGSHPx to allow maintenance of thyroid function.

Aging↗
PubMed1995

Tissue-specific regulation of selenoenzyme gene expression during selenium deficiency in rats.

Regulation of synthesis of the selenoenzymes cytosolic glutathione peroxidase (GSH-Px), phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px) and type-1 iodothyronine 5'-deiodinase (5'IDI) was investigated in liver, thyroid and heart of rats fed on diets containing 0.405, 0.104 (Se-adequate), 0.052, 0.024 or 0.003 mg of Se/kg. Severe Se deficiency (0.003 mg of Se/kg) caused almost total loss of GSH-Px activity and mRNA in liver and heart. 5'IDI activity decreased by 95% in liver and its mRNA by 50%; in the thyroid, activity increased by 15% and mRNA by 95%. PHGSH-Px activity was reduced by 75% in the liver and 60% in the heart but mRNA levels were unchanged; in the thyroid, PHGSH-Px activity was unaffected by Se depletion but its mRNA increased by 52%. Thus there is differential regulation of the three mRNAs and subsequent protein synthesis within and between organs, suggesting both that mechanisms exist to channel Se for synthesis of a particular enzyme and that there is tissue-specific regulation of selenoenzyme mRNAs. During Se depletion, the levels of selenoenzyme mRNA did not necessarily parallel the changes in enzyme activity, suggesting a distinct mechanism for regulating mRNA levels. Nuclear run-off assays with isolated liver nuclei showed severe Se deficiency to have no effect on transcription of the three genes, suggesting that there is post-transcriptional control of the three selenoenzymes, probably involving regulation of mRNA stability.

Animals↗
PubMed1995

Thyroidal extracellular glutathione peroxidase: a potential regulator of thyroid-hormone synthesis.

Human thyrocytes were found to synthesize and secrete the selenoenzyme extracellular glutathione peroxidase (E-GPX), a process which was controlled by the Ca2+/phosphoinositol second-messenger cascade. The potential involvement of thyroidal E-GPX in the regulation of thyroid-hormone synthesis and in the protection of the thyrocyte from peroxidative damage is discussed.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Decreased phospholipid polyunsaturated fatty acid content and superoxide dismutase activity in cardiac muscle of malignant hyperthermia-susceptible swine.

Homogenates of cardiac left ventricle from malignant hyperthermia-susceptible (MHS) pigs produced a circa 72% more pentane than those from malignant hyperthermia-resistant (MHR) animals, indicating enhanced peroxidation of n-6 fatty acids. This is consistent with the observed circa 70% decrease in total phospholipid polyunsaturated fatty acids (PUFA) in MHS compared with MHR tissue, a decrease mainly due to the quantitatively greater loss of n-6 PUFA. Although the percentage loss of n-3 PUFA was greater than that of n-6 PUFA (90% vs 60%), absolute amounts were insufficient to register as ethane production. Three-fold greater phospholipid content of MHS compared with MHR ventricles indicates reduced neutral lipid content probably due to increased catecholamine stimulation. These findings were associated with a small but significant decrease in superoxide dismutase activity in MHS tissues.

Animals↗
PubMed1995

Effect of selenium depletion on thyroidal type-I iodothyronine deiodinase activity in isolated human thyrocytes and rat thyroid and liver.

The effects of dietary selenium deficiency on hepatic and thyroidal type I iodothyronine deiodinase (ID-I) and selenium-dependent glutathione peroxidase (GPx) activities have been studied in weanling rats. In selenium-deficient animals hepatic ID-I activity was reduced to 11% of the activity found in the selenium-replete groups, whilst thyroidal ID-I activity increased by 42%. Hepatic and thyroidal GPx activities were also reduced by selenium deficiency to approximately 0.6 and 70%, respectively, of the values found in the selenium-replete animals. We have also studied the effects of thyrotropin (TSH), and selenium supply on the activity of IDI and GPx in human thyrocytes grown in primary culture. When thyrocytes were grown in selenium-deficient (< 1 nmol l-1 Se) medium in the absence of TSH, addition of sodium selenite up to 1000 nmol l-1 had little or no effect on ID-I activity. In the absence of added selenite, TSH addition produced a significant increase in ID-I activity and this stimulation was increased further when selenite was added at concentrations of 50-1000 nmol l-1 with an optimal effect on ID-I activity being observed at a 500 nmol l-1. Selenium content and GPx activity in human thyrocytes grown in selenium-free media (selenium content < 1 nmol l-1) were not significantly lower than the corresponding measurements made in cells grown in media containing selenium at a concentration of 5.4 nmol l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential control of type-I iodothyronine deiodinase expression by the activation of the cyclic AMP and phosphoinositol signalling pathways in cultured human thyrocytes.

The effects of TSH and the activation of the cyclic AMP (cAMP) and Ca(2+)-phosphatidylinositol (Ca(2+)-PI) cascades on the activity and expression of the selenoenzyme thyroidal type-I iodothyronine deiodinase (ID-I) have been studied using human thyrocytes grown in primary culture. Stimulation of ID-I activity and expression was obtained with TSH and an analogue of cAMP, 8-bromo-cAMP. In the presence or absence of TSH, the addition of the phorbol ester, phorbol 12-myristate 13-acetate (PMA) together with the calcium ionophore A23187, caused a decrease in ID-I activity; a decrease in ID-I expression was also observed as assessed by cell labelling with [75Se]selenite. PMA alone had no effect on ID-I activity in the presence or absence of TSH. A23187 alone produced a small but significant reduction in ID-I activity, but only in TSH-stimulated cells. These data provide evidence that the expression of thyroidal ID-I is negatively regulated by the Ca(2+)-PI cascade, and positively regulated by the cAMP cascade.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1995

Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking.

OBJECTIVE: To quantify the major carotenoids in plasma of Scottish males and establish which were affected by habitual smoking. DESIGN: Concentrations of carotenoids, vitamin C and vitamin E (alpha and gamma-tocopherol) were determined in plasma samples from 50 fasted male smokers and 50 age-matched males who had never smoked (aged 50-59 years). RESULTS: Significantly less alpha-carotene, beta-carotene and beta-cryptoxanthin and vitamin C in plasma of smokers than in never-smokers whereas concentrations of lycopene, lutein/zeaxanthin, phytofluene and vitamin E were similar between the groups. CONCLUSION: Whether lower carotenoid and vitamin C concentrations in smokers than never-smokers reflect different dietary patterns or increased metabolic turnover is unclear but smokers may benefit from increased carotenoid and vitamin C intakes.

Ascorbic Acid↗