INHIBITION OF MICROSOMAL LIPID-PEROXIDATION AND MONOOXYGENASE ACTIVITIES BY EUGENOL
INHIBITION OF MICROSOMAL LIPID-PEROXIDATION AND MONOOXYGENASE ACTIVITIES BY EUGENOL
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DOI：
10.3109/10715769409147521
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发表时间：
1994-01-01
影响因子：
3.3
通讯作者：
LAKSHMAIAH, N
中科院分区：
文献类型：
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作者：
NAGABABU, E;LAKSHMAIAH, N
以前我们报道过丁香酚（4-烯丙基-2-甲氧基苯酚）抑制肝线粒体的非酶过氧化（E。Nagababu和N. Lakshmaiah，1992，生化药理学。43，2393 -2400）。本研究采用Fe ~（3+）-ADP-NADPH、四氯化碳（CCl_4）-NADPH和过氧化氢枯烯（Cumene hydroperoxide，CumOOH）体系，研究了丁香酚对微粒体混合功能氧化酶介导的过氧化反应的影响。在丁香酚的存在下，硫代巴比妥酸反应性物质（TBARS）的形成在所有系统中均减少（IC 50值：Fe+3-ADP-NADPH为14 μ M，CCl 4-NADPH为4.0 μ M，CumOOH为15 μ M）。Fe+3-ADP-NADPH和CumOOH系统对氧摄取也有类似程度的抑制。与其它抗氧化剂的比较结果表明，在Fe+3-ADP-NADPH和CumOOH体系中，抗氧化效果的顺序为：丁基羟基甲苯（BHT）>丁香酚> α-生育酚;在CCl 4-NADPH体系中，抗氧化效果的顺序为：α-生育酚> BHT >丁香酚。丁香酚抑制的时间过程表明干扰的启动以及过氧化的传播。丁香酚不抑制细胞色素P-450还原酶活性，但对氨基比林-N-脱甲基酶、N-亚硝基二甲胺脱甲基酶、苯并（a）芘羟化酶和乙氧基间苯二酚-O-脱乙基酶等P-450连接的单加氧酶活性有不同程度的抑制作用。然而，CumOOH支持的单加氧酶（氨基比林-N-脱甲基酶和苯并（a）芘羟化酶）需要高得多的丁香酚浓度的抑制。在所有体系中，抑制单加氧酶活性所需的丁香酚浓度均大于抑制过氧化反应所需的丁香酚浓度。丁香酚引起微粒体细胞色素P-450谱的1型变化。这些结果表明，丁香酚对脂质过氧化的抑制作用主要是由于其自由基猝灭能力。丁香酚显着保护细胞色素P-450的降解过程中脂质过氧化与所有的系统测试。这些发现表明，丁香酚有可能被用作治疗性抗氧化剂。进一步的评估可能会对这方面有更多的了解。
Previously we reported that eugenol (4-allyl-2-methoxyphenol) inhibits non-enzymatic peroxidation in liver mitochondria (E. Nagababu and N. Lakshmaiah, 1992, Biochemical Pharmacology. 43,2393-2400). In the present study, we examined the effect of eugenol on microsomal mixed function oxidase mediated peroxidation using Fe+3-ADP-NADPH, carbon tetrachloride (CCL4)-NADPH and cumene hydroperoxide (CumOOH) systems. In the presence of eugenol the formation of thiobarbituric acid reactive substances (TBARS) was decreased in all the systems (IC50 values: 14 muM for Fe+3-ADP-NADPH, 4.0 muM for CCl4-NADPH and 15muM for CumOOH). Oxygen uptake was also inhibited to a similar extent with Fe+3-ADP-NADPH and CumOOH systems. A comparative evaluation with other antioxidants showed that in Fe+3-ADP-NADPH and CumOOH systems, the antioxidant efficacy was in the order: butylated hydroxytoluene (BHT) > eugenol > alpha-tocopherol, while in CCl4-NADPH system the order was alpha-tocopherol > BHT > eugenol. Time course of inhibition by eugenol indicated interference in initiation as well as propagation of peroxidation. Eugenol did not inhibit cytochrome P-450 reductase activity but it inhibited P-450 - linked monooxygenase activites such as aminopyrine-N-demethylase, N-nitrosodimethylamine demethylase, benzo(a)pyrene hydroxylase and ethoxyresorurin-O-deethylase to different extents. However, CumOOH supported monooxygenases (aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase) required much higher concentrations of eugenol for inhibition. The concentration of eugenol required to inhibit monooxygenase activities was more than that required to inhibit peroxidation in all the systems. Eugenol elicited type 1 changes in the spectrum of microsomal cytochrome P-450. These results suggest that the inhibitory effect of eugenol on lipid peroxidation is predominantly due to its free radical quenching ability. Eugenol significantly protected against the degradation of cytochrome P-450 during lipid peroxidation with all the systems tested. These findings suggest that eugenol has the potential to be used as a therapeutic antioxidant. Further evaluation may throw more light on this aspect.