Abstract
Recent researches have provided information about the reactions by which myo-inositol (I) is incorporated into phospholipids in animal tissues(1), or is converted to well-known intermediates of carbohydrate metabolism(2), but the physiological significance of these processes is not clear. Since investigations of this kind, and the discovery of additional metabolic pathways, are facilitated by the availability of metabolic antagonists, it seemed of interest to search for an anti-inositol active in animals. On testing a number of cyclitols, some of which had been shown to be antagonists of myo-inositol in certain microorganisms(3), we found that 2-O,C-methylene-myo-inositol (II) was toxic to mice and rats. Our observations on the effects of this compound, and on the suppression of these effects by myo-inositol, are reported here.
Materials and methods. 2-O,C-Methylene-myo-inositol, which hereafter will be designated as myo methylene oxide, was prepared from myo-inosose-2(4) essentially as described by Posternak(5).† Compounds were administered as aqueous solutions by intraperitoneal injection.
Male weanling mice (Taconic strain, Rolfsmeyer Farms) and male weanling rats (Holtzman Co.) were maintained in the departmental animal room for several days before being put on experiment. A low-inositol synthetic diet was used, but is unnecessary. All the effects described are produced equally well in animals fed natural rations.
Results. Four groups of 10 mice each received myo methylene oxide in doses of 100. 125, 135 and 150 mg per kg body weight for the respective groups, and were observed for 5 days, by which time all survivors had resumed growth. A plot of dose vs per cent mortality according to the method of Litchfield and Wilcoxon(6) gave a figure of 123 mg per kg for the LD50 (single dose, intraperitoneal) in mice. Observations on rats showed that the figure is lower for these animals, probably about 70 mg per kg.
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