Williams M, Krootjes B B, van Steveninck J, van der Zee J
Department of Medical Biochemistry, Sylvius Laboratory, Leiden, The Netherlands.
Biochim Biophys Acta. 1994 Mar 24;1211(3):310-6. doi: 10.1016/0005-2760(94)90155-4.
The effect of protoporphyrin on lipid peroxidation in rat liver microsomes was investigated in the presence and absence of light. Protoporphyrin and light stimulated Fe(3+)-ADP/ascorbate-induced lipid peroxidation, whereas Fe(3+)-ADP/NADPH-mediated lipid peroxidation was inhibited. In the dark, on the other hand, protoporphyrin inhibited lipid peroxidation in both systems in a concentration-dependent manner. Protoporphyrin did not affect the reduction of the Fe(3+)-ADP complex by ascorbate, nor did it affect the activity of the NADPH-cytochrome P-450 reductase under these conditions. Uroporphyrin, a hydrophilic porphyrin and not localized in the membrane, did not inhibit lipid peroxidation in the dark in these systems, whereas bilirubin, a well-known radical scavenger and degradation product of protoporphyrin, inhibited lipid peroxidation in both systems. When peroxyl radicals were generated in solution by the azocompound 2,2'-azobis (2-amidino-propane)dihydrochloride lipid peroxidation was inhibited by both porphyrins and bilirubin. Reaction of bilirubin or protoporphyrin, in the presence of microsomes or human serum albumin, with these peroxyl radicals resulted in degradation of both compounds, which could be determined by a decrease in their absorbance at 460 or 407 nm, respectively. These results indicate that the inhibition of lipid peroxidation is most likely caused by scavenging of peroxyl radicals by protoporphyrin. Massive accumulation of protoporphyrin occurs in livers of erythropoietic protoporphyria patients. The fact that protoporphyrin was able to inhibit lipid peroxidation completely at micromolar concentrations also indicates that the deleterious effects of protoporphyrin, observed in these patients, are most likely not mediated by oxidation of lipids.
研究了原卟啉在有光和无光条件下对大鼠肝微粒体脂质过氧化的影响。原卟啉和光刺激了Fe(3+)-ADP/抗坏血酸诱导的脂质过氧化，而Fe(3+)-ADP/NADPH介导的脂质过氧化则受到抑制。另一方面，在黑暗中，原卟啉以浓度依赖的方式抑制了这两种体系中的脂质过氧化。原卟啉不影响抗坏血酸对Fe(3+)-ADP复合物的还原，在这些条件下也不影响NADPH-细胞色素P-450还原酶的活性。尿卟啉是一种亲水性卟啉，不定位在膜中，在黑暗中不抑制这些体系中的脂质过氧化，而胆红素是一种众所周知的自由基清除剂和原卟啉的降解产物，抑制了这两种体系中的脂质过氧化。当通过偶氮化合物2,2'-偶氮双(2-脒基丙烷)二盐酸盐在溶液中产生过氧自由基时，卟啉和胆红素均抑制脂质过氧化。胆红素或原卟啉在微粒体或人血清白蛋白存在下与这些过氧自由基反应导致两种化合物降解，这可以通过它们在460或407 nm处吸光度的降低来确定。这些结果表明，脂质过氧化的抑制很可能是由原卟啉清除过氧自由基引起的。红细胞生成性原卟啉症患者的肝脏中会大量积累原卟啉。原卟啉能够在微摩尔浓度下完全抑制脂质过氧化这一事实也表明，在这些患者中观察到的原卟啉的有害作用很可能不是由脂质氧化介导的。
