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膳食叶酸可预防氧化偶氮甲烷诱导的大鼠结肠异常隐窝病灶形成和氧化应激。

Dietary folate protects against azoxymethane-induced aberrant crypt foci development and oxidative stress in rat colon.

机构信息

Community Health Sciences Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

出版信息

Exp Biol Med (Maywood). 2011 Sep;236(9):1005-11. doi: 10.1258/ebm.2011.011010. Epub 2011 Jul 18.

Abstract

Azoxymethane (AOM) induces cancer and oxidative stress in rat colon. This study tested the hypothesis that dietary folate supplementation protects against AOM-induced oxidative stress and reduces aberrant crypt foci (ACF) development in rat colon. Fifty-four weanling male albino rats, with an average body weight of 50 ± 5 g, were randomly divided into three groups--A, B and C (18 rats per group)--and fed 2, 8 or 40 mg of folic acid per kg of supplemented diets, respectively, throughout the eight weeks' experimental period. The animals were supplied with diet and water ad libitum for four weeks and they reached an average body weight of 100 g. Thereafter each group was then further randomly subdivided into three subgroups (six rats per subgroup): control, vehicle and AOM-injected groups. The control group did not receive any treatment (neither AOM injection nor saline), the rats in the vehicle group were given 1 mL intraperitoneal injection of saline once a week for two weeks and the rats in the AOM-injected group were given two intraperitoneal injections of AOM dissolved in saline once a week for two weeks totaling 30 mg/kg body weight. After the last AOM injection, animals were continuously fed ad libitum their specified diet for two weeks of last AOM injection, all rats were sacrificed, and colon tissues were collected and used for ACF enumeration and measurements of glutathione (GSH) and total antioxidant capacity (TAC). The results revealed that AOM-injected rats showed lower levels of GSH and TAC as compared with control and vehicle groups. Folic acid-supplemented diets suppressed the AOM-induced ACF and GSH depletion in a dose-dependent manner and augmented the TAC. It was concluded that folic acid supplementation protects against the AOM-induced ACF formation by suppressing the AOM-induced GSH depletion in rat colon cells.

摘要

偶氮甲烷(AOM)可诱发大鼠结肠发生癌症和氧化应激。本研究旨在验证以下假设,即膳食叶酸补充可预防 AOM 诱导的氧化应激,并降低大鼠结肠中异常隐窝病灶(ACF)的发展。54 只断奶雄性白化大鼠,平均体重为 50±5g,随机分为三组(A、B 和 C,每组 18 只),分别在整个 8 周实验期间用 2、8 或 40mg 叶酸/kg 补充饮食,动物可自由摄取饮食和水 4 周,体重达到 100g。此后,每组进一步随机分为三组(每组 6 只):对照组、载体组和 AOM 注射组。对照组未接受任何治疗(既未注射 AOM 也未注射生理盐水),载体组大鼠每周腹腔注射 1mL 生理盐水两次,AOM 注射组大鼠每周腹腔注射两次 AOM 溶于生理盐水,每次 30mg/kg 体重,共两次。最后一次 AOM 注射后,动物继续自由摄取其指定的饮食两周,最后一次 AOM 注射结束后,处死所有大鼠,收集结肠组织,用于 ACF 计数以及谷胱甘肽(GSH)和总抗氧化能力(TAC)的测量。结果显示,与对照组和载体组相比,AOM 注射大鼠的 GSH 和 TAC 水平较低。叶酸补充饮食以剂量依赖的方式抑制 AOM 诱导的 ACF 和 GSH 耗竭,并增加 TAC。综上所述,叶酸补充通过抑制 AOM 诱导的大鼠结肠细胞 GSH 耗竭来预防 AOM 诱导的 ACF 形成。

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