Kikuchi Masahiro, Ushida Yusuke, Shiozawa Hirokazu, Umeda Rumiko, Tsuruya Kota, Aoki Yudai, Suganuma Hiroyuki, Nishizaki Yasuhiro
Masahiro Kikuchi, Hirokazu Shiozawa, Rumiko Umeda, Kota Tsuruya, Digestive and Liver Disease Center, Tokai University Tokyo Hospital, Tokyo 153-0065, Japan.
World J Gastroenterol. 2015 Nov 21;21(43):12457-67. doi: 10.3748/wjg.v21.i43.12457.
To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants.
In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme.
Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P < 0.05] and γ-GTP [before: 51.5 (40.8-91.3) vs after: 50.0 (37.8-85.3) IU/L, P < 0.05], as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66 (5.51-9.03) vs after: 5.49 (4.89-6.66) ng/mg-creatinine, P < 0.05]. The reduction of urinary 8-OHdG was significantly correlated with decreased levels of both ALT and γ-GTP [∆8-OHdG and ∆ALT: Spearman r (r) 0.514 and P = 0.012, ∆8-OHdG and ∆γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01).
Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.
评估膳食补充富含萝卜硫素(SF)的西兰花芽苗(BS)提取物对日本男性参与者肝脏异常的影响。
在一项随机、安慰剂对照、双盲试验中,患有脂肪肝的男性参与者接受含葡萄糖异硫氰酸酯[GR;SF的前体(n = 24)]的BS胶囊或安慰剂(n = 28),为期2个月。在试验期前后测量并比较参与者的肝功能指标、血清天冬氨酸和丙氨酸转氨酶(分别为AST和ALT)及γ-谷氨酰转肽酶(γ-GTP)水平,以及氧化应激指标尿8-羟基脱氧鸟苷(8-OHdG)水平。在动物模型中,通过连续4周腹腔注射N-亚硝基二甲胺(NDMA)诱导Sprague-Dawley大鼠发生慢性肝衰竭。同时,大鼠接受添加或不添加BS提取物的AIN-76饮食。此后,处死大鼠,收集其血清和肝脏,以测量血清肝功能指标、肝组织中硫代巴比妥酸反应性物质(TBARS)水平及肝谷胱甘肽S-转移酶(GST)活性,后者是一种典型的Ⅱ相抗氧化酶。
膳食补充含SF前体GR的BS提取物2个月后,血清肝功能指标ALT[中位数(四分位间距),补充前:54.0(34.5 - 79.0)对比补充后:48.5(33.3 - 65.3)IU/L,P < 0.05]和γ-GTP[补充前:51.5(40.8 - 91.3)对比补充后:50.0(37.8 - 85.3)IU/L,P < 0.05]以及碱性磷酸酶活性显著降低。安慰剂对这些指标无显著影响。已确立的氧化应激指标尿8-OHdG水平在接受BS胶囊而非安慰剂的参与者中显著降低[补充前:6.66(5.51 - 9.03)对比补充后:5.49(4.89 - 6.66)ng/mg-肌酐,P < 0.05]。尿8-OHdG的降低与ALT和γ-GTP水平的降低显著相关[∆8-OHdG与∆ALT:斯皮尔曼相关系数(r)0.514,P = 0.012;∆8-OHdG与∆γ-GTP:r = 0.496,P = 0.016]。摄入BS提取物可预防NDMA诱导的大鼠慢性肝衰竭,这归因于通过诱导包括肝GST在内的肝Ⅱ相抗氧化酶抑制了TBARS的升高(86.6 ± 95.2对比107.8 ± 7.7 IU/g,P < 0.01)。
膳食补充含SF前体GR的BS提取物可能通过降低氧化应激对改善肝功能非常有效。