Influence of leukaemia on acetaminophen-induced hepatotoxicity in mice.

J G Lavigne, C d'Auteuil, J M Lavoie
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Abstract

Since it is known that the metabolism of acetaminophen is involved in its hepatotoxicity and that drug metabolizing enzyme activity is decreased in tumor bearing animals, it was of interest to study the influence of L-1210 leukaemia on acetaminophen hepatotoxicity in BDF-1 male mice. A single oral dose of acetaminophen, 125 mg/kg, was given at the fifth day of the mice survival period (7.7 days) and the animals killed twenty-four hours later. As revealed by serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase and lactic dehydrogenase, acetaminophen was less hepatotoxic in leukaemic mice than in control mice by comparison with their own saline group; on the other hand the difference between control and leukaemic mice treated with acetaminophen was significant only for glutamic-pyruvic transaminase. Moreover, we found higher unchanged acetaminophen concentrations in plasma, liver, kidneys, brain and fat of the leukaemic mice as compared to controls, less conjugated metabolites in plasma and liver, decreased in vitro aniline hydroxylation and ethylmorphine N-demethylation. Finally, following acetaminophen administration, reduced hepatic glutathione was depleted to a much lesser extent in the tumor bearing animals than in controls. In conclusion, the L-1210 leukaemia seems to modify the acetaminophen hepatotoxicity and this effect might be explained by decreased acetaminophen biotransformation into toxic metabolites or intermediates.

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白血病对对乙酰氨基酚所致小鼠肝毒性的影响。
由于已知对乙酰氨基酚的代谢参与其肝毒性作用,荷瘤动物体内药物代谢酶活性降低,因此研究L-1210白血病对BDF-1雄性小鼠对乙酰氨基酚肝毒性的影响具有重要意义。在小鼠生存期第5天(7.7天)给予对乙酰氨基酚125 mg/kg单次口服,24小时后死亡。血清谷丙转氨酶、谷草转氨酶和乳酸脱氢酶检测结果显示,对乙酰氨基酚对白血病小鼠的肝毒性低于对照组;另一方面,对乙酰氨基酚治疗的对照组和白血病小鼠之间只有谷丙转氨酶有显著差异。此外,我们发现与对照组相比,白血病小鼠血浆、肝脏、肾脏、大脑和脂肪中不变的对乙酰氨基酚浓度较高,血浆和肝脏中共轭代谢物较少,体外苯胺羟基化和乙基吗啡n -去甲基化减少。最后,在给予对乙酰氨基酚后,荷瘤动物中还原性肝谷胱甘肽的消耗程度远低于对照组。总之,L-1210白血病似乎改变了对乙酰氨基酚的肝毒性,这种影响可能是通过减少对乙酰氨基酚向毒性代谢物或中间体的生物转化来解释的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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Mechanism of action of the sodium pump in vertebrate photoreceptors. Depopulation of lymphocyte migration sites in the lymph node by irradiation and colloidal carbon. Differentiation of bones and skeletal muscles in chick embryos cultured on albumen. [Biology yesterday, today and tomorrow]. [Abstracts of papers presented at the First Biotechnology Colloquium at the University of Montreal, 25-26 March 1983].
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