Guengerich F P, Kim D H
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.
Carcinogenesis. 1990 Dec;11(12):2275-9. doi: 10.1093/carcin/11.12.2275.
Recent in vivo studies in humans have shown a dramatic effect of grapefruit juice in blocking the oxidation of dihydropyridine calcium channel blockers. The flavonoid naringin is the most abundant natural product specific for grapefruit and related citrus--the aglycone naringenin, known to be readily formed from naringin in humans, was found to inhibit the oxidation of the dihydropyridines nifedipine and felodipine in human liver microsomal preparations. These observations were of interest in light of the knowledge that the same human liver cytochrome P450 (IIIA4) appears to be a major catalyst in both nifedipine oxidation and aflatoxin B1 activation. Several flavones inhibited the in vitro activation of aflatoxin B1 in a system employing umuC gene activation due to DNA damage in Salmonella typhimurium TA1535/pSK1002, with naringenin being as effective as any. The high concentration of derivatives of naringenin in certain citrus fruits may be of relevance to cancer chemoprevention involving those carcinogens that are activated by cytochrome P-450IIIA4.
近期针对人类的体内研究表明，葡萄柚汁对二氢吡啶类钙通道阻滞剂的氧化过程具有显著的阻断作用。类黄酮柚皮苷是葡萄柚及相关柑橘类水果中含量最为丰富的天然产物——已知在人体内柚皮苷可轻易转化为苷元柚皮素，研究发现柚皮素能抑制人肝微粒体制剂中硝苯地平和非洛地平这两种二氢吡啶类药物的氧化。鉴于已知相同的人肝细胞色素P450（IIIA4）似乎是硝苯地平氧化及黄曲霉毒素B1激活过程中的主要催化剂，这些观察结果备受关注。在一个利用鼠伤寒沙门氏菌TA1535/pSK1002中因DNA损伤导致umuC基因激活的系统里，几种黄酮类化合物抑制了黄曲霉毒素B1的体外激活，其中柚皮素的效果与其他黄酮类化合物相当。某些柑橘类水果中高浓度的柚皮素衍生物可能与涉及那些由细胞色素P - 450IIIA4激活的致癌物的癌症化学预防有关。
