Iqbal Mohammad, Okada Shigeru
Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-Cho, Okayama 700-8558, Japan.
Pharmacol Toxicol. 2003 Dec;93(6):259-63. doi: 10.1111/j.1600-0773.2003.pto930602.x.
Dietary antioxidants protect laboratory animals against induction of tumours by a variety of chemical carcinogens. Among possible mechanism, protection against chemical carcinogenesis could be mediated via antioxidant-dependent induction of detoxifying enzymes, including quinone reductase and glutathione S-transferase (GSH transferase). Probucol is used cholesterol-lowering drug used in the clinic, with pronounced antioxidant effect that protect against chemical carcinogenesis and toxicity. In the present study we therefore examined the ability of probucol to induce activities of quinone reductase in the cytosolic fractions of various tissues of mice. Quinone reductase activity was increased significantly in 6 of 8 tissues examined from probucol-fed mice. The greatest proportionate increase, to 1.8 times control levels, was observed in liver. Probucol also increased quinone reductase activities of forestomach, heart, kidney, lungs and spleen. Quinone reductase is a major enzyme of xenobiotic metabolism that carries out obligatory two-electron reductions and thereby protects cells against toxicity of quinones. It is induced in many tissues coordinately with other enzymes that protect against electrophilic toxicity. The protective effects of probucol appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the non-oxidative metabolism of a wide variety of xenobiotics. The induction of such enzyme, quinone reductase by probucol suggests the potential value of this compound as a protective agent against chemical carcinogenesis and other forms of electrophilic toxicity. The significance of these results can be implicated in relation to cancer chemopreventive effects of probucol in various target organs.
膳食抗氧化剂可保护实验动物免受多种化学致癌剂诱发肿瘤的影响。在可能的机制中，对化学致癌作用的保护可能是通过抗氧化剂依赖性诱导解毒酶来介导的，这些解毒酶包括醌还原酶和谷胱甘肽S-转移酶（GSH转移酶）。普罗布考是临床上使用的一种降胆固醇药物，具有显著的抗氧化作用，可预防化学致癌作用和毒性。因此，在本研究中，我们检测了普罗布考诱导小鼠各种组织胞质部分醌还原酶活性的能力。在喂食普罗布考的小鼠所检测的8种组织中的6种中，醌还原酶活性显著增加。在肝脏中观察到最大比例的增加，达到对照水平的1.8倍。普罗布考还增加了前胃、心脏、肾脏、肺和脾脏的醌还原酶活性。醌还原酶是外源性物质代谢的一种主要酶，它进行强制性的双电子还原，从而保护细胞免受醌类毒性的影响。它在许多组织中与其他预防亲电毒性的酶协同诱导。普罗布考的保护作用似乎至少部分归因于这种抗氧化剂增加啮齿动物组织中几种参与多种外源性物质非氧化代谢的酶活性的能力。普罗布考对这种酶（醌还原酶）的诱导表明该化合物作为化学致癌作用和其他形式亲电毒性的保护剂具有潜在价值。这些结果的意义可能与普罗布考在各种靶器官中的癌症化学预防作用有关。
