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- W90199810 abstract "The enzyme L-asparaginase, which catalyzes the hydrolysis of the amino acids L-asparagine and L-glutamine to aspartic acid, glutamic acid and ammonia, is useful in the treatment of patients with acute leukemia. However, acute and delayed cerebral dysfunction often occurs in leukemic patients treated by L-asparaginase. Large amounts of L-aspartic acid, L-glutamic acid and ammonia may be liberated by the enzymatic action of L-asparaginase on its substrates L-asparagine and L-glutamine. The ensuing amino acid depletion or its excess may affect brain metabolism and lead to clinical abnormalities. The present paper reports on free amino acid levels and ammonia content in rat serum and cerebral cortex after L-asparaginase administration. Wistar male rats were used throughout this investigation. The acute experimental animals were administered 0.2ml of normal saline containing L-asparaginase (about 500 I.U./Kg B.W.) intraperitoneally and the acute control animals were given 0.2ml of normal saline intraperitoneally. 24h after this single administration, all rats were decapitated, and blood and cortex were collected for the estimation of free amino acids and ammonia. The acute L-asparaginase group showed some significant differences in serum compared to the control group. The most remarkable finding was the absence of asparagine. Aspartic acid and ammonia were elevated significantly; valine and methionine decreased significantly. In the cerebral cortex, aspartic acid and ammonia showed an insignificant change, but some other amino acids serine, glutamine, glycine, GABA and l-methylhistidine were significantly elevated. The chronic experimental group received 0.2ml of saline containing L-asparaginase (about 500 I.U./Kg B.W.) intraperitoneally once a day for 7 consecutive days. The chronic control group received 0.2ml of saline intraperitoneally in the same regime with the experimental group. All rats were fed a ground commercial diet and water ad libitum. The animals were housed in two large cages (the control cage and the experimental cage) in a dark-light room with alernating 12h dark-light cycles. Twenty-four hours after the last administration, all rats were decapitated for collection of blood and cerebral cortex. The chronic L-asparaginase group showed the absence of asparagine and significant increase of aspartic acid in serum similar to the acute L-asparaginase group but an insignificant increase of ammonia in blood. In addition to this finding, threonine, serine, glutamic acid and glycine were elevated significantly. In the cerebral cortex of the chronic L-asparaginase-treated animals, threonine, glycine and l-methylhistidine were significantly elevated compared to the control. It will be difficult to infer from our present data that the cerebral dysfunction induced by L-asparaginase may be correlated mainly with increased levels of aspartic acid, glutamic acid and ammonia in the cerebral cortex." @default.
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- W90199810 date "1978-02-28" @default.
- W90199810 modified "2023-09-26" @default.
- W90199810 title "L-asparaginaseによるラツト血液および脳中の遊離アミノ酸とNH(3)の変化" @default.
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