Schnellmann R G
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
Toxicol Appl Pharmacol. 1989 Jun 1;99(1):11-8. doi: 10.1016/0041-008x(89)90106-3.
2-Bromohydroquinone (BHQ) plays an important role in bromobenzene-induced nephrotoxicity and is a model toxic hydroquinone. Since BHQ has a quinone nucleus and various quinones have been shown to produce cytotoxicity via oxidative stress, the goal of this study was to determine whether BHQ produced cytotoxicity in a suspension of rabbit renal proximal tubules via oxidative stress. t-Butyl hydroperoxide (TBHP), an agent known to produce cytotoxicity via oxidative stress in this preparation, was used as a positive control. BHQ decreased tubular glutathione disulfide content whether glutathione reductase was inhibited or not. Inhibition of glutathione reductase did not result in the potentiation of BHQ-induced mitochondrial dysfunction or cell death. In contrast, TBHP increased tubular glutathione disulfide content. TBHP-induced increases in glutathione disulfide content, mitochondrial dysfunction, and cell death were potentiated when glutathione reductase was inhibited. Unlike TBHP, BHQ did not initiate lipid peroxidation nor was the antioxidant butylated hydroxytoluene protective. However, BHQ and TBHP both increased sodium cyanide-insensitive oxygen consumption. These results suggest that BHQ may undergo "redox cycling," but BHQ-induced mitochondrial dysfunction and cell death are not due to oxidative stress.
2-溴对苯二酚（BHQ）在溴苯诱导的肾毒性中起重要作用，是一种典型的有毒对苯二酚。由于BHQ具有醌核，且各种醌已被证明可通过氧化应激产生细胞毒性，因此本研究的目的是确定BHQ是否通过氧化应激在兔肾近端小管悬浮液中产生细胞毒性。叔丁基过氧化氢（TBHP）是一种已知在该制剂中通过氧化应激产生细胞毒性的试剂，用作阳性对照。无论谷胱甘肽还原酶是否被抑制，BHQ均可降低肾小管谷胱甘肽二硫化物含量。抑制谷胱甘肽还原酶并不会增强BHQ诱导的线粒体功能障碍或细胞死亡。相反，TBHP可增加肾小管谷胱甘肽二硫化物含量。当谷胱甘肽还原酶被抑制时，TBHP诱导的谷胱甘肽二硫化物含量增加、线粒体功能障碍和细胞死亡会增强。与TBHP不同，BHQ不会引发脂质过氧化，抗氧化剂丁基羟基甲苯也无保护作用。然而，BHQ和TBHP均会增加对氰化钠不敏感的氧消耗。这些结果表明，BHQ可能会发生“氧化还原循环”，但BHQ诱导的线粒体功能障碍和细胞死亡并非由氧化应激所致。
