Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione

Whiting, Robert F.; Wei, Lan; Stich, H. F.

doi:10.1016/0165-1218(80)90095-6

Cited by 61 publications

(12 citation statements)

References 19 publications

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“…Even when the synthase is inhibited, sleep may be maintained by the PGD2 already present in the brain until it reaches a level too low to be effective. Some in vitro studies reported previously provide data suggesting that selenocompounds react with thiols such as glutathione and DTT to form products that in turn play a vital role in many metabolic reactions (17)(18)(19)(20). Islam et al (11) also showed in their in vitro study that small amounts of DTT were required for the inhibition of PGD synthase by selenocompounds.…”

Section: Discussionmentioning

confidence: 80%

Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.

Matsumura

Takahata

Hayaishi

1991

Proc. Natl. Acad. Sci. U.S.A.

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Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor in rats, and SeC14 and Na2SeO3 recently have been shown to inhibit the PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2) activity of rat brain. The effect of these selenium compounds on sleep-wake activities was examined in freely moving rats along with their effects on brain temperature, food and water intake, and behavior. Test substances were administered for 6 hr into the third ventricle of rats, using a microdialysis technique. SeC4, time-and dose-dependently, inhibited sleep at perfusion rates of 60 pmol/0.2 jcl per min and higher, and the inhibition was almost complete at rates >200 pmol/0.2 gIl per min. The effect was reversible and was followed by a rebound. Na2SeO3 exhibited similar effects, but Na2SO3 did not show any effect on sleep. Simultaneous administration of dithiothreitol eliminated the sleep-inhibiting effects of these selenium compounds. These findings indicate that the decrease in sleep is due to inhibition of the PGD synthase activity in the brain by SeCL4 as-well as Na2SeO3. During the inhibition of sleep, the rats in general showed an activation of behavior with moderate elevation of brain temperature and a detectable increase in food and water intake, suggesting that the sleep-inhibited state of the rats was similar to the physiological state of wakefulness and that the inhibitory effect was not due to the general toxicity of selenium.Prostaglandins (PGs) D2 and E2, which are the major PGs in the brain of mammals, have been postulated to be endogenous factors for regulating sleep-wake activities in the rat and monkey (1, 2)-the former promoting sleep (3, 4) and the latter augmenting wakefulness (5-7). Naito et al. (8) reported the effects of intracerebroventricularly and systemically administered cyclooxygenase inhibitors such as indomethacin and diclofenac sodium on the sleep-wake activities of rats. However, these inhibitors are not specific for PG0)2 but prevent the synthesis of PGH2 from arachidonate, which in turn affects the consequent production of various eicosanoids, including PGD2 and E2. The rat brain PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2) was purified to homogeneity and characterized by Urade et al. (9,10). More recently, Islam et al. (11) demonstrated in an in vitro study that inorganic quadrivalent selenocompounds, such as SeCL4 and Na2SeO3, inhibited the activity of the rat brain PGD synthase whereas other enzymes in the arachidonate cascade were not affected. Therefore, these selenocompounds may serve as useful probes for elucidating the role of endogenous PGD2 in the physiological sleep-wake regulation.In the present study, the effects of selenocompounds on sleep-wake activities, brain temperature, food and water intake, and behavior were examined in freely moving rats by administration of these compounds into the third ventricle via a microdialysis probe. The results obtained add further support to the hypothesis that PGD2 is involved in the promotion ...

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Section: Discussionmentioning

confidence: 80%

Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.

Matsumura

Takahata

Hayaishi

1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Ganther et al reported a sequence of reactions between selenite and sulfhydryl compounds such as glutathione (GSH) to form hydrogen selenide (Ganther 1966(Ganther , 1968(Ganther , 1971Ganther and Corcoran 1969;Hsieh and Ganther 1975). Selenite cytotoxicity was enhanced by the addition of GSH or tissue extract containing GSH to the culture medium of cultured mammalian cells (Ray and Correspondence to: N. Imura Altenburg 1978; Whiting et al 1980;Batist et al 1986;Snyder 1987). Further, GSH-depleted sheep erythrocytes were not lysed by selenite treatment (Young et al 1981).…”

Section: Introductionmentioning

confidence: 93%

Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes

1993

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Mechanisms of selenite cytotoxicity were examined using isolated rat hepatocytes. When selenite was added to a suspension of rat hepatocytes, intracellular reduced glutathione (GSH) was decreased and the oxygen consumption rate was increased. Subsequently, thiobarbituric acid-reactive substances (TBA-RS) and lactate dehydrogenase (LDH) leakage were increased. A ferric iron chelator, desferrioxamine (DF), and a synthetic superoxide dismutase (SOD) mimic, desferrioxamine manganese (DFMn), reduced the selenite toxicity. These results suggest that superoxide anion and its reactive metabolites such as the hydroxyl radical may be involved in the cytotoxicity of selenite.

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“…However, according to the available literature, the toxicity of selenium toward animal cells and yeast cells shares many features. For instance, with animal cells: (i) thiols have been observed to enhance the accumulation of selenium (66 -68) and the toxicity of selenite (21,66,69); (ii) hydrogen selenide toxicity has been recognized very early (70); and (iii) redox phenomena (24,25,71) as well as mitochondria (72) are involved in the toxicity mechanisms of selenocompounds. Interestingly, in bacteria also, redox phenomena are involved in the toxicity of selenite (73).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Production of Hydrogen Selenide Accounts for Thiol-assisted Toxicity of Selenite against Saccharomyces cerevisiae

Tarze¹,

Dauplais²,

Grigoras³

et al. 2007

Journal of Biological Chemistry

124

125

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Administration of selenium in humans has anticarcinogenic effects. However, the boundary between cancer-protecting and toxic levels of selenium is extremely narrow. The mechanisms of selenium toxicity need to be fully understood. In Saccharomyces cerevisiae, selenite in the millimolar range is well tolerated by cells. Here we show that the lethal dose of selenite is reduced to the micromolar range by the presence of thiols in the growth medium. Glutathione and selenite spontaneously react to produce several selenium-containing compounds (selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium) as well as reactive oxygen species. We studied which compounds in the reaction pathway between glutathione and sodium selenite are responsible for this toxicity. Involvement of selenodiglutathione, elemental selenium, or reactive oxygen species could be ruled out. In contrast, extracellular formation of hydrogen selenide can fully explain the exacerbation of selenite toxicity by thiols. Indeed, direct production of hydrogen selenide with D-cysteine desulfhydrase induces high mortality. Selenium uptake by S. cerevisiae is considerably enhanced in the presence of external thiols, most likely through internalization of hydrogen selenide. Finally, we discuss the possibility that selenium exerts its toxicity through consumption of intracellular reduced glutathione, thus leading to severe oxidative stress.

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Unscheduled DNA synthesis and chromosome aberrations induced by inorganic and organic selenium compounds in the presence of glutathione

Cited by 61 publications

References 19 publications

Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.

Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase.

Possible involvement of active oxygen species in selenite toxicity in isolated rat hepatocytes

Extracellular Production of Hydrogen Selenide Accounts for Thiol-assisted Toxicity of Selenite against Saccharomyces cerevisiae

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