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西兰花芽提取物诱导解毒相关基因表达并减轻急性肝损伤。

Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury.

作者信息

Yoshida Kazutaka, Ushida Yusuke, Ishijima Tomoko, Suganuma Hiroyuki, Inakuma Takahiro, Yajima Nobuhiro, Abe Keiko, Nakai Yuji

机构信息

Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.

出版信息

World J Gastroenterol. 2015 Sep 21;21(35):10091-103. doi: 10.3748/wjg.v21.i35.10091.

Abstract

AIM

To investigate the effects of broccoli sprout extract (BSEx) on liver gene expression and acute liver injury in the rat.

METHODS

First, the effects of BSEx on liver gene expression were examined. Male rats were divided into two groups. The Control group was fed the AIN-76 diet, and the BSEx group was fed the AIN-76 diet containing BSEx. After a 10-d feeding period, rats were sacrificed and their livers were used for DNA microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. Next, the effects of BSEx on acute liver injury were examined. In experiments using acute liver injury models, 1000 mg/kg acetaminophen (APAP) or 350 mg/kg D-galactosamine (D-GalN) was used to induce injury. These male rats were divided into four groups: Control, BSEx, Inducer (APAP or D-GalN), and Inducer+BSEx. The feeding regimens were identical for the two analyses. Twenty-four hours following APAP administration via p.o. or D-GalN administration via i.p., rats were sacrificed to determine serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, hepatic glutathione (GSH) and thiobarbituric acid-reactive substances accumulation and glutathione-S-transferase (GST) activity.

RESULTS

Microarray and real-time RT-PCR analyses revealed that BSEx upregulated the expression of genes related to detoxification and glutathione synthesis in normal rat liver. The levels of AST (70.91 ± 15.74 IU/mL vs 5614.41 ± 1997.83 IU/mL, P < 0.05) and ALT (11.78 ± 2.08 IU/mL vs 1297.71 ± 447.33 IU/mL, P < 0.05) were significantly suppressed in the APAP + BSEx group compared with the APAP group. The level of GSH (2.61 ± 0.75 nmol/g tissue vs 1.66 ± 0.59 nmol/g tissue, P < 0.05) and liver GST activity (93.19 ± 16.55 U/g tissue vs 51.90 ± 16.85 U/g tissue, P < 0.05) were significantly increased in the APAP + BSEx group compared with the APAP group. AST (4820.05 ± 3094.93 IU/mL vs 12465.63 ± 3223.97 IU/mL, P < 0.05) and ALT (1808.95 ± 1014.04 IU/mL vs 3936.46 ± 777.52 IU/mL, P < 0.05) levels were significantly suppressed in the D-GalN + BSEx group compared with the D-GalN group, but the levels of AST and ALT in the D-GalN + BSEx group were higher than those in the APAP + BSEx group. The level of GST activity was significantly increased in the D-GalN + BSEx group compared with the D-GalN group (98.04 ± 15.75 U/g tissue vs 53.15 ± 8.14 U/g tissue, P < 0.05).

CONCLUSION

We demonstrated that BSEx protected the liver from various types of xenobiotic substances through induction of detoxification enzymes and glutathione synthesis.

摘要

目的

研究西兰花芽提取物(BSEx)对大鼠肝脏基因表达及急性肝损伤的影响。

方法

首先,检测BSEx对肝脏基因表达的影响。将雄性大鼠分为两组。对照组喂食AIN - 76饮食,BSEx组喂食含BSEx的AIN - 76饮食。经过10天的喂养期后,处死大鼠,取肝脏进行DNA微阵列和实时逆转录 - 聚合酶链反应(RT - PCR)分析。接下来,检测BSEx对急性肝损伤的影响。在使用急性肝损伤模型的实验中,用1000 mg/kg对乙酰氨基酚(APAP)或350 mg/kg D - 半乳糖胺(D - GalN)诱导损伤。将这些雄性大鼠分为四组:对照组、BSEx组、诱导剂组(APAP或D - GalN)和诱导剂 + BSEx组。两种分析的喂养方案相同。经口服给予APAP或经腹腔注射给予D - GalN 24小时后,处死大鼠以测定血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平、肝脏谷胱甘肽(GSH)和硫代巴比妥酸反应性物质蓄积以及谷胱甘肽 - S - 转移酶(GST)活性。

结果

微阵列和实时RT - PCR分析显示,BSEx上调正常大鼠肝脏中与解毒和谷胱甘肽合成相关基因的表达。与APAP组相比,APAP + BSEx组的AST(70.91±15.74 IU/mL对5614.41±1997.83 IU/mL,P < 0.05)和ALT(11.78±2.08 IU/mL对1297.71±447.33 IU/mL,P < 0.05)水平显著降低。与APAP组相比,APAP + BSEx组的GSH水平(2.61±0.75 nmol/g组织对1.66±0.59 nmol/g组织,P < 0.05)和肝脏GST活性(93.19±16.55 U/g组织对51.90±16.85 U/g组织,P < 0.05)显著升高。与D - GalN组相比,D - GalN + BSEx组的AST(4820.05±3094.93 IU/mL对12465.63±3223.97 IU/mL,P < 0.05)和ALT(1808.95±1014.04 IU/mL对3936.46±777.52 IU/mL,P < 0.05)水平显著降低,但D - GalN + BSEx组的AST和ALT水平高于APAP + BSEx组。与D - GalN组相比,D - GalN + BSEx组的GST活性显著升高(98.04±15.75 U/g组织对53.15±8.14 U/g组织,P < 0.05)。

结论

我们证明BSEx通过诱导解毒酶和谷胱甘肽合成保护肝脏免受各种外源性物质的侵害。

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