Cytoprotective and antioxidant effects of boldine on tert-butyl hydroperoxide-induced damage to isolated hepatocytes
Cytoprotective and antioxidant effects of boldine on tert-butyl hydroperoxide-induced damage to isolated hepatocytes
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DOI：
10.1007/bf00143359
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发表时间：
1996-04-01
影响因子：
6.1
通讯作者：
Speisky, H
中科院分区：
文献类型：
--
作者：
Bannach, R;Valenzuela, A;Speisky, H
Boldine 是一种阿朴啡生物碱，我们最近发现它具有有效的抗氧化特性。我们在此报告，Boldine 浓度依赖性地抑制叔丁基过氧化氢 (TBOOH) 诱导的离体大鼠肝细胞的过氧化（硫代巴比妥酸反应物质的积累）和溶解损伤（台盼蓝排除和乳酸脱氢酶泄漏）。 Boldine (200 mu mol/L) 在浓度等于或低于 0.87 mmol/L 时具有完全的细胞保护作用并完全阻止 TBOOH 诱导的过氧化反应。然而，在过氧化物浓度为0.91 mmol/L时，虽然博尔丁完全抑制脂质过氧化，但它基本上不能提供针对TBOOH的细胞保护作用。单独使用 TBOOH (0.83 mmol/L) 会导致还原型谷胱甘肽早期（60 秒内）突然下降（50%），而氧化型谷胱甘肽水平相应增加。同时添加细胞保护和抗氧化浓度的博尔丁（200 μmol/L）并不能阻止这些作用。延迟向悬浮液中添加博尔丁（10或20分钟后）虽然有效阻止硫代巴比妥酸反应物质的任何进一步增加，但完全未能防止过氧化物诱导的细胞活力丧失。相反，将肝细胞与博尔丁预孵育 150 分钟（此时在细胞内或细胞外空间均检测不到博尔丁）可防止脂质过氧化，并且在保护细胞免受随后添加 TBOOH 造成的损伤方面，与在对照条件下向预孵育 150 分钟的肝细胞同时添加博尔丁和 TBOOH 一样有效。
Boldine, an aporphine alkaloid, was recently shown by us to exhibit potent antioxidant properties. We report here that boldine concentration-dependently inhibited the peroxidative (accumulation of thiobarbituric acid reactive substances) and lytic damage (trypan blue exclusion and lactate dehydrogenase leakage) to isolated rat hepatocytes induced by tert-butyl hydroperoxide (TBOOH). Boldine (200 mu mol/L) fully cytoprotected and completely prevented the peroxidation induced by TBOOH at concentrations equal to or lower than 0.87 mmol/L. However, at a peroxide concentration of 0.91 mmol/L, although boldine completely inhibited lipid peroxidation it largely failed to afford cytoprotection against TBOOH. TBOOH alone (0.83 mmol/L) caused an early (within 60 s) sudden decline of reduced glutathione (by 50%) and an equivalent increase in the levels of oxidized glutathione. Neither of these effects was prevented by the simultaneous addition of a cytoprotective and antioxidant concentration of boldine (200 mu mol/L). The delayed addition of boldine to the suspension (after 10 or 20 min), while effectively blocking any further increase in thiobarbituric acid reactive substances, totally failed to prevent the peroxide-induced loss in cell viability. Conversely, preincubation of the hepatocytes with boldine for 150 min (at which time no boldine could be detected in either intra- or extracellular spaces) prevented lipid peroxidation and was as effective in protecting the cells against the damage caused by the subsequent addition of TBOOH as the simultaneous addition of boldine and TBOOH to hepatocytes preincubated for 150 min under control conditions.