Tryptophan-niacin metabolism in rat with puromycin aminonucleoside-induced nephrosis

Tryptophan-niacin metabolism in rat with puromycin aminonucleoside-induced nephrosis
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DOI:
10.1024/0300-9831.76.1.28
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发表时间:
2006-01-01
影响因子:
2.3
通讯作者:
Sanada, Hiroo
Sanada, Hiroo
中科院分区:
医学4区
文献类型:
--
作者:
Egashira, Yukari;Nagaki, Shin;Sanada, Hiroo

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本研究探讨嘌呤霉素氨基糖苷PAN致肾病大鼠体内烟酰胺-烟酸代谢的变化,以及引起尿中烟酰胺及其代谢产物排泄量变化的机制,以及肾脏在烟酰胺-烟酸转化中的作用。PAN处理的大鼠以100 mg/kg体重的剂量用1.0%(w/v)PAN溶液腹膜内注射一次。在PAN注射后8天收集24小时尿。每日尿中烟酰胺及其代谢产物的排泄量,肝脏和血液中的NAD,和关键酶的活性,烟酸代谢。在PAN处理的大鼠中,烟酰胺及其代谢产物的尿排泄总量显著低于对照组。与对照组相比,PAN处理组的肾脏α-氨基-β-羧基粘康酸-ε-半醛脱羧酶(ACMSD)活性显著降低50%。尽管肾脏ACMSD活性降低,但PAN处理的大鼠中色氨酸向烟酸的转化倾向于较低。在肾病大鼠中,烟酸的尿排泄减少和色氨酸向烟酸的转化可能导致血液色氨酸水平降低。肾脏ACMSD活性的作用可能是最小的关于在本实验条件下的鼠李糖-烟酸转化。
We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidney alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.