title: Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  We demonstrated that BSEx protected the liver from various types of xenobiotic substances through induction of detoxification enzymes and glutathione synthesis.
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ushida
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishijima
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suganuma
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inakuma
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yajima
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
authors.affiliation: Kazutaka Yoshida, Yusuke Ushida, Hiroyuki Suganuma, Nobuhiro Yajima, Research and Development Division, Kagome Co., Ltd., Nasushiobara 329-2762, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakai
mesh_terms: D000082:Acetaminophen; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001937:Brassica / Q000737:chemistry*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005688:Galactosamine; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D036226:Seedlings; D013997:Time Factors
chemical_list: D015415:Biomarkers; D010936:Plant Extracts; D020011:Protective Agents; D000082:Acetaminophen; D005688:Galactosamine; D005978:Glutathione
keywords: Acetaminophen; Acute liver injury; Broccoli sprout; DNA microarray; Galactosamine; Glucoraphanin; Sulforaphane