Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.; PY1988;Thomas Jefferson University, USA (美國);_WJD_2019-0902_V001R01_IR94_

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2019-09-02

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.; PY1988;Thomas Jefferson University, USA (美國);_WJD_2019-0902_V001R01_IR94_RvD20190902_

Source (資訊來源):

https://www.ncbi.nlm.nih.gov/pubmed/3421709

Info cited on 2019-09-02-WD1 (資訊引用於 中華民國108年9月2日) by 湯偉晉 (WeiJin Tang)

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Arch Biochem Biophys. 1988 Sep;265(2):311-20.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Toxic consequence of the abrupt depletion of glutathione (穀胱甘肽) in cultured rat hepatocytes.

Miccadei S1, Kyle ME, Gilfor D, Farber JL.

Author information

1

Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

Thomas Jefferson University, USA (美國)

Abstract

Cultured hepatocytes were exposed to two chemicals, dinitrofluorobenzene (DNFB) and diethyl maleate (DEM), that abruptly deplete cellular stores of glutathione (穀胱甘肽). Upon the loss of GSH, lipid peroxidation was evidenced by an accumulation of malondialdehyde in the cultures followed by the death of the hepatocytes. Pretreatment of the hepatocytes with a ferric iron chelator, deferoxamine, or the addition of an antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD), to the culture medium prevented both the lipid peroxidation and the cell death produced by either DNFB or DEM. However, neither deferoxamine nor DPPD prevented the depletion of GSH caused by either agent. Inhibition of glutathione (穀胱甘肽) reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or inhibition of catalase by aminotriazole sensitized the hepatocytes to the cytotoxicity of DNFB. In a similar manner, pretreatment with BCNU potentiated the cell killing by DEM. DPPD and deferoxamine protected hepatocytes pretreated with BCNU and then exposed to DNFB or DEM. These data indicate that an abrupt depletion of GSH leads to lipid peroxidation and cell death in cultured hepatocytes. It is proposed that GSH depletion sensitizes the hepatocyte to its constitutive flux of partially reduced oxygen species. Such an oxidative stress is normally detoxified by GSH-dependent mechanisms. However, with GSH depletion these activated oxygen species are toxic as a result of the iron-dependent formation of a potent oxidizing species.

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抽象

將培養的肝細胞暴露於兩種化學物質，即二硝基氟苯（DNFB）和馬來酸二乙酯（DEM），其突然耗盡穀胱甘肽的細胞儲存。在GSH喪失後，脂質過氧化通過培養物中丙二醛的積累隨後肝細胞的死亡得到證實。用鐵螯合劑，去鐵胺或添加抗氧化劑N，N'-二苯基 - 對苯二胺（DPPD）預處理肝細胞，防止DNFB產生的脂質過氧化和細胞死亡或DEM。然而，去鐵胺和DPPD均未阻止任何一種藥物引起的GSH耗竭。 1,3-雙（2-氯乙基）-1-亞硝基脲（BCNU）對穀胱甘肽還原酶的抑製或氨基三唑對過氧化氫酶的抑制使肝細胞對DNFB的細胞毒性敏感。以類似的方式，用BCNU預處理增強了DEM對細胞的殺傷作用。 DPPD和去鐵胺保護用BCNU預處理的肝細胞，然後暴露於DNFB或DEM。這些數據表明GSH的突然耗盡導致培養的肝細胞中的脂質過氧化和細胞死亡。提出GSH耗竭使肝細胞對其部分還原的氧物種的組成型通量敏感。這種氧化應激通常通過GSH依賴性機制解毒。然而，隨著GSH耗盡，這些活化的氧物質由於鐵依賴性形成有效的氧化物質而具有毒性。

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PMID: 3421709 DOI: 10.1016/0003-9861(88)90133-6

[Indexed for MEDLINE]

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