da Silva Maria E F, Meirelles Nilce C
Laboratory of Biomembranes, Department of Biochemistry, Institute of Biology, State University of Campinas, CP6109, ZIP CODE 13083-970, Cidade Universitária Zeferino Vaz, Barão Geraldo, Campinas, SP, Brazil.
Toxicol In Vitro. 2004 Dec;18(6):859-67. doi: 10.1016/j.tiv.2004.04.006.
Cytochromes P450 (CYP) constitute a superfamily of hemeproteins that play a vital role in the metabolism of a wide variety of endogenous and xenobiotic compounds. Xenobiotic metabolism and the role of CYP are of particular interest in studies regarding the prevention of the damage caused by chemical pollutants. We investigated, in this study, the interaction of Triton X-100 and Tween 80 with CYP and antioxidant defenses in Curimbata, a Brazilian fish. Aiming to clarify the effects of non-ionic surfactants in the monooxigenase system of fish through in vitro study, the effects of Triton X-100 and Tween 80 were analyzed using monooxygenases and antioxidant system as experimental model. Total CYP and EROD were strongly inhibited by Triton X-100 and Tween 80 in a concentration-dependent way; the content of CYP was reduced until zero while EROD activity was completely inhibited in the presence of Triton X-100 and more than 40% inhibited in the presence of Tween 80. Each surfactant causes a different effect on each antioxidant enzyme. No effect was detected in SOD activity in the presence of even Triton X-100 or Tween 80. Triton X-100 increase catalase activity, while Tween 80 decreases this enzyme activity. The molecular structure of the surfactants causes the alteration of this system, since they are able to interact with the microsomal protein, especially with monooxigenase's components, altering their conformation and, consequently destroying their function. Our results suggest that surfactants can interact with components of the microsomal system leading to inhibition of CYP. Therefore, CYP activity, which has been used as a biomarker of xenobiotic exposure, should be used as a marker in association with other enzymes.
细胞色素P450（CYP）构成了一个血红素蛋白超家族，在多种内源性和外源性化合物的代谢中起着至关重要的作用。在关于预防化学污染物造成损害的研究中，外源性物质代谢及CYP的作用尤为令人关注。在本研究中，我们调查了曲拉通X-100和吐温80与巴西鱼类库里姆巴塔鱼体内CYP及抗氧化防御的相互作用。旨在通过体外研究阐明非离子表面活性剂对鱼类单加氧酶系统的影响，以单加氧酶和抗氧化系统作为实验模型分析了曲拉通X-100和吐温80的作用。曲拉通X-100和吐温80以浓度依赖性方式强烈抑制总CYP和EROD；CYP含量降低至零，而在曲拉通X-100存在时EROD活性完全被抑制，在吐温80存在时被抑制超过40%。每种表面活性剂对每种抗氧化酶产生不同的影响。即使在曲拉通X-100或吐温80存在下，也未检测到超氧化物歧化酶（SOD）活性有变化。曲拉通X-100增加过氧化氢酶活性，而吐温80降低该酶活性。表面活性剂的分子结构导致了该系统的改变，因为它们能够与微粒体蛋白相互作用，尤其是与单加氧酶的组分相互作用，改变其构象，从而破坏其功能。我们的结果表明，表面活性剂可与微粒体系统的组分相互作用，导致CYP受到抑制。因此，曾被用作外源性物质暴露生物标志物的CYP活性，应与其他酶联合用作标志物。
