Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid.

Assessment of mitochondrial function in vivo with a breath test utilizing alpha-ketoisocaproic acid.
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使用 α-酮异己酸通过呼吸测试评估体内线粒体功能。

DOI:
10.1002/hep.1840100513
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发表时间:
1989
期刊:
Hepatology (Baltimore, Md.)
影响因子:
--
通讯作者:
Lauterburg,BH
Lauterburg,BH
中科院分区:
--
文献类型:
--
作者:
Michaletz,PA;Cap,L;Alpert,E;Lauterburg,BH

文献摘要

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在大鼠体内评价呼吸试验以评估肝线粒体功能。腹腔注射[1 - 14 C]-α-酮异己酸后,14 CO2呼出在10 - 20 min内达到峰值,然后呈指数下降,半衰期为14.3 min。对照动物在1 h内呼出了给药放射性的38.6%。在功能性无肝动物中,呼吸中的14 CO2为对照动物的23%,表明α-酮异己酸脱羧反应主要反映体内肝线粒体功能。乙醇(3 g/kg)显著降低了α-酮异己酸脱羧(1小时内呼吸中出现21.8%的剂量),可能是由于乙醇诱导的NAD+:NADH比率变化。相反,线粒体呼吸的解偶联剂水杨酸钠(375 mg/kg)增加了α-酮异己酸的脱羧作用(1小时内以14 CO2的形式恢复了56.3%的剂量)。4-戊烯酸诱导的线粒体损伤降低了α-酮异己酸的脱羧,但不影响安替比林的微粒体代谢。目前的数据表明,α-酮异己酸呼气试验提供了一种体内肝线粒体功能的非侵入性估计,当应用于人体时,可能会产生临床有用的信息。
A breath test to assess hepatic mitochondrial functionin vivowas evaluated in rats. Following the i.p. administration of [1‐14C]‐α‐ketoisocaproic acid,14CO2exhalation reached a peak within 10 to 20 min and then declined exponentially, with a half‐life of 14.3 min. Control animals exhaled 38.6% of the administered radioactivity within 1 hr. In functionally anhepatic animals,14CO2in breath amounted to 23% of that in control animals, indicating that α‐ketoisocaproic acid decarboxylation reflects mainly hepatic mitochondrial functionin vivo. Ethanol (3 gm per kg) significantly decreased α‐ketoisocaproic acid decarboxylation (21.8% of the dose appearing in breath in 1 hr), probably due to the ethanol‐induced shift in the NAD+:NADH ratio. In contrast, an uncoupler of mitochondrial respiration, sodium salicylate (375 mg per kg), increased the decarboxylation of α—ketoisocaproic acid (56.3% of the dose recovered as14CO2in 1 hr). Mitochondrial damage induced by 4‐pentenoic acid decreased the decarboxylation of α‐ketoisocaproic acid but did not affect the microsomal metabolism of antipyrine. The present data indicate that the α‐ketoisocaproic acid breath test provides a noninvasive estimate of hepatic mitochondrial functionin vivowhich, when applied to man, might yield clinically useful information.