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Screening of stimulatory effects of dietary risk factors on mouse intestinal cell kinetics

机译:饮食风险因子对小鼠肠道细胞动力学刺激作用的筛选

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摘要

AIM: Although epidemiological and experimental studies validate influence of genetic, environmental and dietary factors in the causation of various types of cancers including colon, results from all these sources are inconclusive. Hypothesizing that high fat diet and obesity are among the major predisposing factors in the incidence of colon cancer, we evaluated the role of diet constituted with food material derived from a tropical plant, Tamarindus indica Linn (TI).METHODS: A two part randomized double-blind study was conducted employing inbred Swiss albino mice from a single generation for the whole investigation. One day-old neonates (n = 12) were subcutaneously administered with monosodium glutamate (MSG) to induce obesity (OB). At weaning these animals were maintained on modified AIN-76 diet supplemented with 10% TI and 10% fat bolus (w/w, TIFB) for 8 wk. Subsequently, in the second part of study, four groups of animals belonging to the same generation, age and gender (n = 12 per group), were maintained on: AIN-76 control diet (CD); AIN-76 mixed with 10% TI extract (TI); and, mixed with 10% TI and 10% FB (TIFB) for 8 wk, to determine intestinal crypt cell proliferation, functionally-specific enzyme activities, fermentation profile, and energy preferences.RESULTS: We observed a significant increase in the crypt cell production rate in distal colonic segment of experimental animals when compared with the controls. This segment also contained significantly low butyrate levels compared to control and TIFB groups. All the experimental groups showed a gross decrease in the enzyme activities viz., succinate dehydrogenase, acid-galactosidase and dipeptidyl amino peptidase IV demonstrating pathological stress caused by the test regimens, and an altered metabolic flux in the cellular environment.CONCLUSION: We have demonstrated a cumulative response to the three dietary factors, one of which (TI) is reported, herein, for the first time to modulate kinetics of large intestinal mucosa, contributing to total risk posed by these test agents.
机译:目的:尽管流行病学和实验研究证实了遗传,环境和饮食因素对包括结肠在内的各种类型癌症的影响,但所有这些来源的结果尚无定论。假设高脂饮食和肥胖是结肠癌发病率的主要诱因之一,我们评估了饮食由热带植物罗望子(Tamarindus indica Linn,TI)衍生的食物构成的作用。方法:两部分随机双重整个研究采用单代瑞士近交白化病小鼠进行的盲研究。一天大的新生儿(n = 12)皮下注射谷氨酸钠(MSG)以诱导肥胖(OB)。断奶时,将这些动物维持在改良的AIN-76饮食中,并补充10%TI和10%脂肪团(w / w,TIFB),持续8周。随后,在研究的第二部分中,按相同的年龄,性别(每组​​n = 12)对四组动物进行饲养:AIN-76对照饮食(CD); AIN-76与10%TI提取物(TI)混合;然后与10%TI和10%FB(TIFB)混合8周,以确定肠道隐窝细胞的增殖,功能特异性酶活性,发酵曲线和能量偏好。结果:我们观察到隐窝细胞产量显着增加与对照组相比,实验动物远端结肠节段的血流速度与对照组和TIFB组相比,该部分的丁酸盐含量也很低。所有实验组均显示出酶活性的总体下降,即琥珀酸脱氢酶,酸半乳糖苷酶和二肽基氨基肽酶IV的降低,证明了测试方案引起的病理性应激,以及细胞环境中代谢通量的改变。结论:我们已经证明了本文首次报道了对三种饮食因素的累积反应,其中一种(TI)被报道来调节大肠黏膜的动力学,从而增加了这些试验药物的总风险。

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