膳食类黄酮和其他多酚类物质的苯氧自由基的促氧化活性及细胞效应。

Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics.

作者信息

Galati Giuseppe, Sabzevari Omid, Wilson John X, O'Brien Peter J

机构信息

Department of Pharmacology, Faculty of Pharmacy, University of Toronto, 19 Russell St., Toronto, Ontario, Canada M5S 2S2.

出版信息

Toxicology. 2002 Aug 1;177(1):91-104. doi: 10.1016/s0300-483x(02)00198-1.

DOI:10.1016/s0300-483x(02)00198-1

PMID:12126798

Abstract

Dietary polyphenolics in fruits, vegetables, wines, spices and herbal medicines have beneficial antioxidant, anti-inflammatory and anticancer effects. However, we have observed that dietary polyphenolics with phenol rings were metabolized by peroxidase to form prooxidant phenoxyl radicals which, in some cases were sufficiently reactive to cooxidize GSH or NADH accompanied by extensive oxygen uptake and reactive oxygen species formation. The order of catalytic effectiveness found for oxygen activation when polyphenolics were metabolized by peroxidase in the presence of GSH was phloretin>phloridzin>4,2'-dihydroxy chalcone>p-coumaric acid>naringenin>apigenin>curcumin>resveratrol>isoliquiritigenin>capsaicin>kaempferol. Ascorbate was also cooxidized by the phenoxyl radicals but without oxygen activation. Polyphenolics with catechol rings also cooxidized ascorbate, likely mediated by semiquinone radicals. The order of catalytic effectiveness found for ascorbate cooxidation was fisetin luteolin, quercetin, >eriodictyol, caffeic acid, nordihydroguaiaretic acid>catechin>taxifolin, catechol. NADH was stoichiometrically oxidized without oxygen uptake which, suggests that o-quinone metabolites were responsible. GSH was not cooxidized and GSH conjugates were formed, likely mediated by the o-quinone metabolites. Incubation of hepatocytes with dietary polyphenolics containing phenol rings was found to partially oxidize hepatocyte GSH to GSSG while polyphenolics with a catechol ring were found to deplete GSH through formation of GSH conjugates. Dietary polyphenolics with phenol rings also oxidized human erythrocyte oxyhemoglobin and caused erythrocyte hemolysis more readily than polyphenolics with catechol rings. It is concluded that polyphenolics containing a phenol ring are generally more prooxidant than polyphenolics containing a catechol ring.

摘要

水果、蔬菜、葡萄酒、香料和草药中的膳食多酚具有有益的抗氧化、抗炎和抗癌作用。然而，我们观察到带有酚环的膳食多酚会被过氧化物酶代谢形成促氧化苯氧自由基，在某些情况下，这些自由基具有足够的反应活性，能够共氧化谷胱甘肽（GSH）或烟酰胺腺嘌呤二核苷酸（NADH），同时伴随着大量的氧气摄取和活性氧的形成。当多酚在谷胱甘肽存在下被过氧化物酶代谢时，发现其激活氧气的催化效率顺序为：根皮素＞根皮苷＞4,2'-二羟基查耳酮＞对香豆酸＞柚皮素＞芹菜素＞姜黄素＞白藜芦醇＞异甘草素＞辣椒素＞山奈酚。抗坏血酸也会被苯氧自由基共氧化，但不会激活氧气。带有儿茶酚环的多酚也会共氧化抗坏血酸，可能是由半醌自由基介导的。抗坏血酸共氧化的催化效率顺序为：漆黄素＞木犀草素、槲皮素＞圣草酚、咖啡酸、去甲二氢愈创木酸＞儿茶素＞紫杉叶素、儿茶酚。NADH按化学计量被氧化，且没有氧气摄取，这表明邻醌代谢产物是其原因。谷胱甘肽不会被共氧化，而是形成了谷胱甘肽共轭物，可能是由邻醌代谢产物介导的。发现用含有酚环的膳食多酚孵育肝细胞会使肝细胞中的谷胱甘肽部分氧化为氧化型谷胱甘肽（GSSG），而带有儿茶酚环的多酚则会通过形成谷胱甘肽共轭物来消耗谷胱甘肽。含有酚环的膳食多酚还会氧化人红细胞中的氧合血红蛋白，并且比带有儿茶酚环的多酚更容易引起红细胞溶血。结论是，含有酚环的多酚通常比含有儿茶酚环的多酚更具促氧化作用。