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- W1567583428 abstract "The effect of 4′-demethyl-epipodophyllotoxin 9-(4,6- O -2-thenylidene-β-d-glucopyranoside) (VM26), an epipodophyllotoxin with oncolytic activity, on hepatic intermediary metabolism and on plasma levels of glucose and protein was studied after mice were treated with the drug on Days 0, 3, and 6. Glucose metabolism by liver slices, as well as the consumption of oxygen by isolated hepatic mitochondria, were assayed at weekly intervals after three i.p. injections of drug (6, 10, or 16 mg/kg of body weight). By Day 14, treatment with VM26 caused a decrease of 50% in the oxidation of glucose via the hexose monophosphate pathway and an increase of 60% in oxidation via the Embden-Meyerhof pathway. These alterations in the metabolism of glucose persisted throughout the remainder of the study. The oxidations of α-ketoglutarate and of isocitrate by mitochondria were irreversibly inhibited by approximately 75% from Day 7 after the administration of 6, 10, or 16 mg of VM26 per kg. At 6 and 10 mg/kg, the oxidation of succinate was depressed less than the oxidation of either α-ketoglutarate or isocitrate. In addition, delayed toxicity was also observed after treatment with a combination of Adriamycin and VM26 at dosages of the latter that alone failed to produce the syndrome. The present evidence indicates that VM26 compromises hepatic intermediary metabolism, that the treated mouse is incapable of producing the necessary energy required for maintenance of normal liver function, and that this negative balance eventually leads to death of the animals in spite of a normal dietary intake." @default.
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- W1567583428 date "1977-09-01" @default.
- W1567583428 modified "2023-10-14" @default.
- W1567583428 title "VM26-induced changes in hepatic intermediary metabolism of mice." @default.
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