Effect of ascorbic acid esters on hepatic glutathione levels in mice treated with a hepatotoxic dose of acetaminophen.
Effect of ascorbic acid esters on hepatic glutathione levels in mice treated with a hepatotoxic dose of acetaminophen.
复制标题
抗坏血酸酯对用肝毒性剂量的对乙酰氨基酚治疗的小鼠肝脏谷胱甘肽水平的影响。
DOI：
10.1002/jbt.2570060203
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
D. R. Bourcier
中科院分区：
文献类型：
--
作者：
A. Mitra;A. Kulkarni;V. Ravikumar;D. R. Bourcier
对乙酰氨基酚（APAP）与或不与抗坏血酸硬脂酸酯（AS）或抗坏血酸棕榈酸酯（AP）通过管饲法给予雄性Swiss-Webster小鼠，每种化学品的剂量为600 mg/kg。在APAP和APAP + AP或AS给药后监测肝毒性生化标志物、血清转氨酶（血清谷丙转氨酶[SGPT]、血清谷草转氨酶[SGOT]）和血清异柠檬酸脱氢酶（SICD）活性。与APAP阳性对照相比，APAP- +抗坏血酸酯处理的动物血清转氨酶和SICD活性显著降低。APAP与AP或AS口服联合给药不能阻止初始肝GSH耗竭（给药后15分钟-4小时）。然而，肝脏GSH含量开始上升，在APAP + AS或AP处理的动物在4小时，并达到对照值在12小时内给药后。当在给药后60分钟内测量时，APAP + AP或AS处理动物的尿巯基尿酸结合物也显著高于APAP单独处理动物。血浆磺基溴酞（BSP）的保留是约8倍高，在APAP治疗的动物相比，APAP +抗坏血酸酯治疗表明维持肝脏排泄功能的存在下AP或AS。预先用马来酸二乙酯（DEM）耗竭肝脏GSH并不改变AP或AS在APAP存在下的保肝作用。肝脏抗坏血酸水平也在APAP + AP或AS处理后4小时达到峰值。L-抗坏血酸酯在GSH再生后共同管理的肝毒性剂量和APAP的可能作用进行了讨论。
Acetaminophen (APAP) with or without ascorbyl stearate (AS) or ascorbyl palmitate (AP) was administered by gavage to male Swiss-Webster mice at a dose of 600 mg/kg for each chemical. The biochemical markers of hepatotoxicity, serum transaminases (serum glutamate pyruvate transaminase [SGPT], serum glutamate oxaloacetic transaminase [SGOT]) and serum isocitrate dehydrogenase (SICD) activities were monitored after APAP and APAP + AP or AS dosing. There were significant reductions in serum transaminase and SICD activities in the APAP- + ascorbate ester-treated animals as compared to APAP-positive controls. Oral coadministration of APAP with AP or AS did not prevent the initial hepatic GSH depletion (15 min-4 hr postdosing). However, hepatic GSH content began to rise in the APAP + AS or AP-treated animals at 4 hr and reached control values within 12 hr postdosing. Urinary mercapturate conjugates were also significantly higher in the APAP + AP or AS-treated animals as compared to APAP alone when measured over a 60-min postdosing period. Plasma sulfobromophthalein (BSP) retention was approximately eight times higher in APAP-treated animals as compared to the APAP + ascorbate ester treatments indicating maintenance of hepatic excretory functions in presence of AP or AS. Prior depletion of hepatic GSH by diethyl maleate (DEM) did not alter hepatoprotective effects of AP or AS in the presence of APAP. Hepatic ascorbate levels also peaked at 4 hours after APAP + AP or AS treatments. The possible role of L-ascorbic acid esters in GSH regeneration following co-administration of a hepatotoxic dose and APAP is discussed.