Vanamala Jairam, Leonardi Tety, Patil Bhimanagouda S, Taddeo Stella S, Murphy Mary E, Pike Leonard M, Chapkin Robert S, Lupton Joanne R, Turner Nancy D
Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA.
Carcinogenesis. 2006 Jun;27(6):1257-65. doi: 10.1093/carcin/bgi318. Epub 2005 Dec 29.
This study evaluated the hypothesis that untreated and irradiated grapefruit as well as the isolated citrus compounds naringin and limonin would protect against azoxymethane (AOM)-induced aberrant crypt foci (ACF) by suppressing proliferation and elevating apoptosis through anti-inflammatory activities. Male Sprague-Dawley rats (n = 100) were provided one of five diets: control (without added grapefruit components), untreated or irradiated (300 Gy, 137Cs) grapefruit pulp powder (13.7 g/kg), naringin (200 mg/kg) or limonin (200 mg/kg). Rats were injected with saline or AOM (15 mg/kg) during the third and fourth week and colons were resected (6 weeks post second injection) for evaluation of ACF, proliferation, apoptosis, and cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein levels. Experimental diets had no effect on the variables measured in saline-injected rats. However, in AOM-injected rats, the experimental diets suppressed (P < or = 0.02) aberrant crypt and high multiplicity ACF (HMACF; P < or = 0.01) formation and the proliferative index (P < or = 0.02) compared with the control diet. Only untreated grapefruit and limonin suppressed (P < or = 0.04) HMACF/cm and expansion (P < or = 0.008) of the proliferative zone that occurred in the AOM-injected rats consuming the control diet. All diets elevated (P < or = 0.05) the apoptotic index in AOM-injected rats, compared with the control diet; however, the greatest enhancement was seen with untreated grapefruit and limonin. Untreated grapefruit and limonin diets suppressed elevation of both iNOS (P < or = 0.003) and COX-2 (P < or = 0.032) levels observed in AOM-injected rats consuming the control diet. Although irradiated grapefruit and naringin suppressed iNOS levels in AOM-injected rats, no effect was observed with respect to COX-2 levels. Thus, lower levels of iNOS and COX-2 are associated with suppression of proliferation and upregulation of apoptosis, which may have contributed to a decrease in the number of HMACF in rats provided with untreated grapefruit and limonin. These results suggest that consumption of grapefruit or limonin may help to suppress colon cancer development.
未经处理和经辐照的葡萄柚以及分离出的柑橘类化合物柚皮苷和柠檬苦素，通过抗炎活性抑制细胞增殖并提高细胞凋亡率，从而预防由氧化偶氮甲烷（AOM）诱导的异常隐窝灶（ACF）。将100只雄性Sprague-Dawley大鼠分为五组，分别给予五种饮食之一：对照组（不添加葡萄柚成分）、未经处理或经辐照（300 Gy，137Cs）的葡萄柚果肉粉（13.7 g/kg）、柚皮苷（200 mg/kg）或柠檬苦素（200 mg/kg）。在第三周和第四周给大鼠注射生理盐水或AOM（15 mg/kg），并在第二次注射后6周切除结肠，以评估ACF、细胞增殖、细胞凋亡以及环氧化酶（COX）-2和诱导型一氧化氮合酶（iNOS）蛋白水平。实验饮食对注射生理盐水的大鼠所测变量无影响。然而，在注射AOM的大鼠中，与对照饮食相比，实验饮食抑制了（P≤0.02）异常隐窝和高倍数ACF（HMACF；P≤0.01）的形成以及增殖指数（P≤0.02）。只有未经处理的葡萄柚和柠檬苦素抑制了（P≤0.04）食用对照饮食的注射AOM大鼠中出现的HMACF/cm以及增殖区的扩展（P≤0.008）。与对照饮食相比，所有饮食均提高了（P≤0.05）注射AOM大鼠的凋亡指数；然而，未经处理的葡萄柚和柠檬苦素的效果最为显著。未经处理的葡萄柚和柠檬苦素饮食抑制了食用对照饮食的注射AOM大鼠中观察到的iNOS（P≤0.003）和COX-2（P≤0.032）水平的升高。尽管辐照后的葡萄柚和柚皮苷抑制了注射AOM大鼠中的iNOS水平，但未观察到对COX-2水平的影响。因此，较低水平的iNOS和COX-2与增殖抑制和凋亡上调相关，这可能导致了给予未经处理的葡萄柚和柠檬苦素的大鼠中HMACF数量的减少。这些结果表明，食用葡萄柚或柠檬苦素可能有助于抑制结肠癌的发展。
