Biomedical subjects
Publications and source records attributed to S Orrenius.
The effect of extracellular Ca2+ concentration on ethanol oxidation and drug metabolism was studied in isolated rat hepatocytes. Both ethanol oxidation and drug glucuronidation showed similar dependence upon Ca2+, which was a stimulation of activity as Ca2+ was increased to physiological concentration, and inhibition at higher concentration.
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Methods for quantitation of catalase, cytochromes P-450 and b5 and mitochondrial cytochromes a + a3, b561 + b566, and c + c1 in isolated hepatocytes were developed in analogy to methods established for subcellular systems and were used to measure changes in specific hemoprotein concentrations due to pretreatment and to change in incubation conditions. Pretreatment of rats with phenobarbital or 3-methylcholanthrene resulted in increased concentrations of cytochromes P-450 and b5 on a cellular basis, but had no effect on the other hemoproteins. Chronic ethanol pretreatment resulted in increased cytochrome P-450 and decreased cytochromes a + a3 concentrations. Hemoprotein concentrations in hepatocytes decreased following 4-10-h incubations in rotating round-bottom flasks. Rates of decrease were dependent upon both incubation conditions and prior in vivo treatments with phenobarbital or 3-methylcholanthrene.
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The accumulation of 99Tcm-gluconate in the myocardium and liver of the rat during anoxia has been investigated on the cellular level and compared with the histopathologic changes. The conclusion is drawn that the uptake of isotope runs a course similar to that registered in vivo in human myocardial infarction.
A rapid method for isolation of cells from the small intestine of the rat resulted in a preparation where 95--100% of the cells excluded NADH or trypan blue. Isolated intestinal cells catalyzed the cytochrome P-450 dependent metabolism of benzo(a)pyrene, harmine, ethoxyresorufin and ethoxycoumarin. Isolation of intestinal cells 24 hours after a single oral dose of 3-methylcholanthrene resulted in 25--45-fold increases in benzo(a)pyrene, ethoxycoumarin and ethoxyresorufin metabolism, whereas the rate of demethylation of harmine was doubled. Harmine metabolism led to the formation of harmol which was subsequently conjugated with glucuronic acid. Very little sulphate conjugate was detected. Intestinal cells catalyzed glucuronidation of 1- and 2-naphthol at a linear rate for up to one hour. Glucuronidation of 1- and 2-naphthol was saturated at 50 muM, whereas a concentration of 800 muM was necessary for saturation of harmol glucuronidation. Intestinal cells metabolized paracetamol to the glucuronide, sulphate, glutathione and cysteine conjugates. The latter two are evidence of cytochrome-P-450-dependent metabolic activation of paracetamol by intestinal cells.
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