Glucose-14 C-UL metabolism in man after abrupt altitude exposure (4,300 m).
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Biomedical subjects
Publications and source records attributed to R F Burk.
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Selenoprotein P is a newly characterized selenoprotein. It is the first protein described to contain multiple selenocysteines. It is secreted by the liver into the plasma and turns over rapidly. Its concentration is sensitive to the selenium status of the animal. Its function is unknown.
Selenium deficiency causes a number of hepatic metabolic alterations in the rat which could lead to changes in chemical toxicity. It causes a decrease in glutathione peroxidase activity, an increase in glutathione S-transferase activity, and an increase in the rate of glutathione synthesis. The hepatotoxicities of three compounds which bind to glutathione S-transferase; iodipamide, acetaminophen, and aflatoxin B1, are decreased by selenium deficiency. The toxicity of redox cycling compounds is generally increased by selenium deficiency and is accompanied by evidence of lipid peroxidation. Thus, nitrofurantoin (100 mg/kg) causes renal tubular necrosis in selenium-deficient rats but not in controls. Selenium-deficient rats are much more sensitive to diquat toxicity than are controls. Lethality of diquat in selenium-deficient rats appears to be causally linked to lipid peroxidation. Lethality of diquat in control rats is not linked to lipid peroxidation. The effect of selenium does not appear to be mediated by glutathione peroxidase, however, indicating that selenium has another oxidant defense function. Another interesting observation made was that increases in inspired O2 tension decreased ethane production (lipid peroxidation) in selenium-deficient and in control rats given diquat. Thus, O2 appears to prevent diquat-induced lipid peroxidation.
Selenium in human nutrition was the theme of the 1986 Research Workshop of the American Society for Parenteral and Enteral Nutrition. At the workshop, evidence for the nutritional essentiality of selenium to humans was reviewed, and it was concluded that Keshan disease, the cardiomyopathy of children and young women described in China, is now firmly linked to selenium deficiency, although other factors may be involved. Selenium metabolism and techniques for assessing selenium status also received attention at the workshop. A measurement of blood selenium levels was accepted, in general, as a valid technique for assessing selenium status in individuals with relatively constant selenium intakes. Clinical practitioners at the workshop reported that some of their total parenteral nutrition patients not receiving selenium presented biochemical evidence of selenium deficiency, but no characteristic clinical syndrome due to selenium deficiency has yet been observed in such patients. The workshop attendees acknowledged the need for an official guideline for selenium use in total parenteral nutrition, but were unable to develop a consensus regarding such a guideline. However, the workshop agreed that any guideline established in the future should specify the type of patients to be supplemented, the dose of selenium to be administered, and the selenium compound to be used. Until that time, the physician supervising the therapy must assume responsibility both for determining the need for selenium supplementation, and for the administration of the supplemental selenium.
Pentane excretion in breath has been used as an index of lipid peroxidation in intact animals based on the premise that the hydrocarbon is metabolically inert. However, it is now known that pentane is metabolized by animals and that its pulmonary excretion is affected both by its production and by its metabolism. Thus, changes in pentane metabolism could obscure alterations in the rate of production, which is the quantity most closely related to the extent of lipid peroxidation. The purpose of this study was to determine the clearance of pentane from arterial blood by the rat following an injection of the hydrocarbon into a closed chamber containing the animal. Clearance was estimated from the analysis of arterial blood and chamber air concentration-time curves using a three-compartment model which included the chamber as a peripheral compartment. The required blood-to-air partition coefficients were determined experimentally. Blood clearance values obtained from control rats, rats pretreated with carbon tetrachloride, and animals given 4-methylpyrazole were 0.141, 0.021, and 0.014 liter/min/kg, respectively. The 85% decrease in clearance of animals pretreated with either a metabolic inhibitor or a toxin which destroys cytochrome P-450 suggests that metabolism may contribute significantly to the overall elimination of pentane. Therefore, the quantitation of pentane excretion rate as an index of lipid peroxidation should include a consideration of possible changes in metabolic clearance.
The pulmonary excretion rates of ethane and pentane have been used as indices of lipid peroxidation. This use assumes that exhalation of these hydrocarbons is directly related to their formation rate. This is true only if the elimination (metabolism plus nonpulmonary excretion) of ethane and pentane are constant in the presence of alterations in lipid peroxidation. However, the in vivo metabolic elimination profile for pentane is unknown and it has not been established with certainty that ethane is metabolized in vivo. Radiolabeled [14C]ethane and pentane were used to study the disposition of these hydrocarbons when injected into an enclosed chamber system containing a rat. The ethane and pentane concentrations in chamber air measured as 14C radioactivity were in general agreement with more selective measurements based on GC analysis. Pentane was cleared from chamber air at a much faster rate than ethane. Approximately 50 and 19.8% of the total radioactivity added to the chamber as [14C]pentane or [14c]ethane, respectively, was recovered as carbon dioxide at the end of 8 hr. The fraction of total radioactivity recovered in urine was 7.6 and 1.0% for the pentane and ethane experiments, respectively. These results indicate unequivocally that both ethane and pentane are metabolized in the intact rat.