Heme metabolism in liver and spleen of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-treated rats.
Heme metabolism in liver and spleen of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-treated rats.
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1-(2-氯乙基)-3-环己基-1-亚硝基脲 (CCNU) 治疗大鼠肝脏和脾脏中的血红素代谢。
DOI：
10.1016/0006-2952(84)90073-x
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发表时间：
1984
影响因子：
5.8
通讯作者：
Ahmed,AE
中科院分区：
文献类型：
--
作者：
el-Azhary,RA;Ahmed,AE
本文研究了亚硝基脲类抗癌烷化剂1-（2-氯乙基）-3-环己基-1-亚硝基脲（CCNU）对肝、脾血红素代谢相关酶的影响。单次口服50或100 mg/kg的CCNU引起脾和肝重量的时间依赖性减轻。CCNU处理（100 mg/kg）后7天，体重分别为对照组的45%和65%。CCNU处理7天后，脾脏和肝脏中血红素合成的限速酶δ-氨基乙酰丙酸合成酶（ALA-S）的活性分别下降到对照值的11%和24%。血红素氧合酶活性，血红素分解的限速酶，在CCNU给药后在肝脏和脾脏中适度增加。在肝脏中，血红素加氧酶活性在24小时是对照值的142%，在脾脏中，活性在1周时是对照的180%。用苯巴比妥（PB）（40 mg/kg/天，i. p.）CCNU处理4天后，肝脏重量的下降出现逆转，但对脾脏重量的下降没有影响。同样，PB预处理逆转了CCNU给药后肝脏ALA-S活性的下降，但对脾脏ALA-S活性的下降没有影响。本研究表明，CCNU引起脾和肝血红素生物合成酶活性的显着下降。PB预处理可逆转CCNU对肝脏的血液毒性，而对脾脏的血液毒性无明显影响。
The effect of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), an anticancer alkylating agent of the nitrosourea group, on liver and spleen enzymes involved in the control of heme metabolism was studied. A single oral dose of 50 or 100 mg/kg CCNU caused a time-dependent loss in weight of both spleen and liver. Seven days after CCNU treatment (lOO mg/kg) the weights were at 45 and 65% of controls respectively. The activity of δ-aminolevulinic acid synthetase (ALA-S), the rate-limiting enzyme in heme biosynthesis, declined in spleen and liver to 11 and 24% of control values, respectively, 7 days after CCNU treatment. Heme oxygenase activity, the rate-limiting enzyme of heme breakdown, was moderately increased in liver and spleen following CCNU administration. In liver, heme oxygenase activity was 142% of control values at 24 hr, and in spleen the activity was 180% of controls at 1 week. Pretreatment of the animals with phenobarbital (PB) (40 mg/kg/day, i.p.) for 4 days caused a reversal in the decline of liver weight with no effect on the decline in spleen weight following CCNU treatment. Similarly, PB pretreatment reversed the decline in hepatic ALA-S activity after CCNU administration but had no effect on the decline in splenic ALA-S activity. This study indicates that CCNU causes significant decreases in the activity of enzymes of heme biosynthesis in spleen and liver. The CCNU hemotoxicity in the liver was reversed by PB pretreatment whereas the splenic hemotoxicity was unchanged.