推测的谷胱甘肽耗竭剂对兔近端肾小管的多种作用。

Multiple effects of presumed glutathione depletors on rabbit proximal tubules.

作者信息

Schnellmann R G, Mandel L J

出版信息

Kidney Int. 1986 Apr;29(4):858-62. doi: 10.1038/ki.1986.77.

DOI:10.1038/ki.1986.77

Abstract

The role of glutathione (GSH) in the protection of normal renal function has been investigated using rabbit proximal tubules. Compounds known to deplete GSH in various biological systems by alkylation (via GSH S-transferases, phorone; 2-cyclohexen-1-one, CHX; diethyl maleate, DEM) or by inhibiting GSH synthesis (buthionine sulfoximine, BSO) were added to suspensions of proximal tubules and incubated for 60 min. BSO (1 or 5 mM) did not decrease GSH concentrations, O2 consumption, or cause lactate dehydrogenase release (LDH). Concentrations of CHX (2 mM) and phorone (10 mM) that decreased GSH concentrations also inhibited O2 consumption and caused LDH release. DEM (10 mM) did not significantly decrease GSH concentrations but did inhibit oxygen consumption and cause slight LDH release. Time-course studies using CHX (3 mM) showed that GSH levels and O2 consumption decreased as early as 15 min while LDH release did not occur until 60 min. These results show that: there may be a relationship between O2 consumption and GSH levels; agents that have been used historically to reduce GSH concentrations have other cytotoxic effects; and rabbit renal proximal tubules appear to be resistant to GSH depletion.

摘要

利用兔近端小管研究了谷胱甘肽（GSH）在保护正常肾功能中的作用。通过烷基化（经由谷胱甘肽S -转移酶，佛尔酮；2 -环己烯 - 1 -酮，CHX；马来酸二乙酯，DEM）或抑制GSH合成（丁硫氨酸亚砜胺，BSO）在各种生物系统中已知会消耗GSH的化合物被添加到近端小管悬浮液中并孵育60分钟。BSO（1或5 mM）并未降低GSH浓度、耗氧量，也未导致乳酸脱氢酶释放（LDH）。降低GSH浓度的CHX（2 mM）和佛尔酮（10 mM）浓度也抑制了耗氧量并导致LDH释放。DEM（10 mM）并未显著降低GSH浓度，但确实抑制了氧消耗并导致轻微的LDH释放。使用CHX（3 mM）的时间进程研究表明，早在15分钟时GSH水平和耗氧量就降低了，而LDH释放直到60分钟才发生。这些结果表明：耗氧量与GSH水平之间可能存在关联；历史上用于降低GSH浓度的试剂具有其他细胞毒性作用；并且兔肾近端小管似乎对GSH耗竭具有抗性。