Metabolomics of urine for the assessment of microvesicular lipid accumulation in the liver following isoniazid exposure.
Metabolomics of urine for the assessment of microvesicular lipid accumulation in the liver following isoniazid exposure.
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DOI：
10.1007/s11306-010-0197-8
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发表时间：
2010-06-01
期刊：
影响因子：
3.6
通讯作者：
Fennell, Timothy R.
中科院分区：
文献类型：
--
作者：
Sumner, Susan J.;Burgess, Jason P.;Snyder, Rodney W.;Popp, James A.;Fennell, Timothy R.
这项研究是为了开发一种非侵入性的肝脏微泡脂肪堆积(MVLA)的标记物，这是一种目前在肝活检后诊断为人类的组织病理学效应。在对化学品和药物的动物研究中检测到MVLA，并在一些接触化学品或药物的人类中发生。由于MVLA是一种可逆的组织病理学，使用非侵入性方法及早检测MVLA可以帮助临床医生治疗服用已知导致这种损伤的药物的患者。异烟肼(INH)被选为本次研究的模型化合物，因为MVLA发生在接受包括异烟肼在内的联合治疗的结核病(TB)患者中。这项研究使用的是雄性大鼠，每天服用异烟肼0、10或300 mg/kg，持续8天。分别于第1天和第8天取尿、血、肝组织标本。核磁共振代谢组学显示，在给予大剂量异烟肼8天的4/9只大鼠中，尿液中的标志物与右、左和正中肝叶的MVLA结果相关(100%)。肝脏提取物的代谢组学也揭示了与MVLA损伤相关的标志物。临床上用于评估肝损伤的血清酶与MVLA的结果并不一致。代谢产物的改变与MVLA的存在相一致，与肌醇、碳水化合物、甘油脂和乙醛酸代谢的中断相关。这项研究揭示了可以在临床前使用的标记物，提供了对MVLA相关机制的见解，并证明了在人类患者中验证非侵入性MVLA标记物的必要性。
This study was conducted to develop a noninvasive marker of hepatic microvesicular lipid accumulation (MVLA), a histopathological effect currently diagnosed in humans following liver biopsy. MVLA is detected in animal studies of chemicals and drugs and occurs in some humans exposed to chemicals or pharmaceuticals. Because MVLA is a reversible histopathology, early detection of MVLA using a noninvasive method, could aid clinicians in the treatment of patients taking drugs that are known to induce this injury. Isoniazid (INH) was selected as a model compound for this investigation, because MVLA occurs in tuberculosis (TB) patients treated with a combination therapy, which includes INH. This study used male rats dosed daily with INH at 0, 10, or 300 mg/kg/day for up to 8 days. Urine, blood, and liver were obtained following 1 and 8 days. NMR metabolomics of urine revealed markers that correlated (100%) with the findings of MVLA in the right, left, and median liver lobes in 4/9 rats administered the high dose of INH for 8 days. Metabolomics of liver extracts also revealed markers that correlated with the MVLA injury. Serum enzymes that are clinically used to assess liver injury were not consistently correlated to the findings of MVLA. Metabolite changes consistent with the presence of MVLA correlated with interruptions in inositol, carbohydrate, glycerolipid, and glyoxylate metabolism. This study reveals markers that could find pre-clinical use, provides insights into mechanisms involved in MVLA, and demonstrates the need for the validation of noninvasive MVLA markers in human patients.
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影响因子：
2.9
作者：
Argyrou, Argyrides;Jin, Lianji;Blanchard, John S.
通讯作者：
Blanchard, John S.
影响因子：
4.6
作者：
Russo, MW;Galanko, JA;Watkins, P
通讯作者：
Watkins, P
DOI：
10.1016/0005-2744(70)90054-9
发表时间：
1970-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
NAKATANI, Y;FUJIOKA, M;HIGASHINO, K
通讯作者：
HIGASHINO, K
影响因子：
4.2
作者：
YEH, YY;ZEE, P
通讯作者：
ZEE, P
影响因子：
7.4
作者：
Weljie, Aalim M.;Newton, Jack;Slupsky, Carolyn M.
通讯作者：
Slupsky, Carolyn M.