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

doi:10.3748/wjg.v21.i35.10091

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastroenterol. Sep 21, 2015; 21(35): 10091-10103
Published online Sep 21, 2015. doi: 10.3748/wjg.v21.i35.10091

Table 1 Compositions of AIN-76 and broccoli sprout diet

Ingredients	Control diet (AIN-76)	BSEx diet
Casein	25.00%	25.00%
Cornstarch	40.10%	33.86%
Sucrose	20.00%	20.00%
Corn oil	5.00%	5.00%
Mineral mixture	3.50%	3.50%
Vitamin mixture	1.00%	1.00%
Choline bitartrate	0.40%	0.40%
Cellulose	5.00%	5.00%
BSEx
Glucoraphanin	-	0.34%
Others	-	5.90%

Others include unknown compounds such as protein, fiber, sugar, fat, etc.

Table 2 Primers used for real-time polymerase chain reaction analysis

Gene symbol	Sequence (5'→3')
Rpl10a	Forward	GAAGAAGGTGCTGTGTTTGGC
Rpl10a	Reverse	TCGGTCATCTTCACGTGGC
Arbp	Forward	GGCGACCTGGAAGTCCAACTA
Arbp	Reverse	CATTGTCTGCTCCCACAATGAA
Rpl15	Forward	GCTTTAGTAGCAGCTGGTGTGTGA
Rpl15	Reverse	ACCCAAGACGAATTGATTGGAA
Rps16	Forward	TCCAAGGGTCCGCTGCAGTC
Rps16	Reverse	CGTTCACCTTGATGAGCCCATT
Rpl3	Forward	TGTATTGGAGCTTGGCATCCTG
Rpl3	Reverse	ACCATCCTTGATGAGGTAGCCTTG
Rps18	Forward	AAGTTTCAGCACATCCAGCGAGTA
Rps18	Reverse	TTGGTGAGGTCAATGTCTGCTTTC
Rps3	Forward	GATCATGTGAGCATTGTGGAACCTA
Rps3	Reverse	CTCCAGATGCAGCTGCCAAG
Cyp1a2	Forward	TCAACCTCGTGAAGAGCAGCA
Cyp1a2	Reverse	GTCCTGGATACTGTTCTTGTTGAAGTC
Gstm1	Forward	TTCGTGCAGACATTGTGGAGA
Gstm1	Reverse	CTTGCCCAGGAACTCAGAGTAGA
Gclc	Forward	GTGGACACCCGATGCAGTATTC
Gclc	Reverse	CATCCACCTGGCAACAGTCATTAG
Gsta3	Forward	AATAGGCTGAGCAGGGCTGATG
Gsta3	Reverse	GGTTGCTGACTCTGGTTCTCAGG
Gstt3	Forward	ATGCCTTTGCCCAGGTGAAC
Gstt3	Reverse	GTGTGCTGCCAAGCCAGGTA
Gstp1	Forward	GAGGACCTTCGATGCAAATATGGTA
Gstp1	Reverse	CTGGGACAGCAGGGTCTCAA

Table 3 Significantly enriched Kyoto Encyclopedia of Genes and Genomes pathway found in the differentially expressed genes by broccoli sprout extract (P < 0.05)

	KEGG ID	Pathway	FDR-corrected P value
Up-regulated	rno03010	Ribosome	3.97 × 10^-43
	rno00980	Metabolism of xenobiotics by cytochrome P450	0.001186149
	rno00982	Drug metabolism	0.004009591
Down-regulated	rno00071	Fatty acid metabolism	2.42 × 10^-17
	rno03320	PPAR signaling pathway	2.42 × 10^-12
	rno00280	Valine, leucine and isoleucine degradation	5.75 × 10^-8
	rno00620	Pyruvate metabolism	8.79 × 10^-7
	rno01040	Biosynthesis of unsaturated fatty acids	8.34 × 10^-7
	rno00650	Butanoate metabolism	1.21 × 10^-6
	rno00830	Retinol metabolism	5.97 × 10^-6
	rno00982	Drug metabolism	7.15 × 10^-6
	rno00640	Propanoate metabolism	1.06 × 10^-5
	rno00020	Citrate cycle (TCA cycle)	4.94 × 10^-5
	rno00120	Primary bile acid biosynthesis	5.63 × 10^-5
	rno00140	Steroid hormone biosynthesis	7.09 × 10^-4
	rno00561	Glycerolipid metabolism	7.78 × 10^-4
	rno00010	Glycolysis/gluconeogenesis	0.003660561
	rno00380	Tryptophan metabolism	0.003952492
	rno00983	Drug metabolism	0.004286518
	rno00500	Starch and sucrose metabolism	0.009275005
	rno00980	Metabolism of xenobiotics by cytochrome P450	0.024561245

FDR: False discovery rate.

Table 4 Significant canonical pathways (P < 0.05) in upregulated genes induced by broccoli sprout extract

Ingenuity canonical pathways	-log(B-H P value)	Ratio	Molecules
EIF2 signaling	22.5	0.1830	RPL18, RPL14, RPLP0, RPL7, Rpl7a, RPL41, RPS4X, RPS12, RPL22L1, RPL31, RPS26, RPS13, RPL15, RPS16, RPS7, RPS19, RPS6, RPS15A, RPL11, RPS2, RPS5, RPL26, RPS18, RPL34, RPSA, RPL13, Gm11425, RPS9, RPS3, RPS23, RPL23A, RPL27A, RPS8, RPL18A, RPS11, RPL3, RPLP2
Regulation of eIF4 and p70S6K Signaling	7.57	0.1150	RPS18, RPS12, RPS4X, RPS26, RPS13, RPSA, RPS3, RPS16, RPS9, RPS7, RPS23, PPP2CA, RPS19, RPS6, RPS8, ITGB1, RPS15A, RPS11, RPS2, RPS5
mTOR Signaling	6.49	0.1000	RND3, RPS18, RPS12, RPS4X, HMOX1, RPS26, RPS13, RPSA, RPS3, RPS16, RPS9, RPS7, RPS23, PPP2CA, RPS19, RPS6, RPS8, RPS15A, RPS11, RPS2, RPS5
Nrf2-mediated oxidative stress response	3.85	0.0890	GPX2, GSTM5, ACTG1, AKR1A1, GCLC, HSPB8, GSTP1, GSTA1, HMOX1, GSTM1, FTL, JUN, EPHX1, NFE2L2, AKR7A3, ACTB, NQO1
Metabolism of xenobiotics by cytochrome P450	3.84	0.0612	GSTM5, GSTM1, Gstt3, CYP2B6, AKR1A1, UGT2B15, Cyp2c40, CYP1A2, GSTP1, GSTA1, AKR1C3, UGT2B4
Glutathione metabolism	2.88	0.0899	GPX2, GSTM5, GSTM1, Gstt3, GCLC, PRDX6, GSTP1, GSTA1
Arachidonic acid metabolism	2.09	0.0485	GPX2, LTC4S, CYP2B6, CYP4A22, PRDX6, PLA2G2A, Cyp2c40, PLA2G16, CYP1A2, AKR1C3
Acute phase response signaling	2.00	0.0734	APOA1, A2M, C4BPA, SERPINA3, RBP7, C4B, HMOX1, ORM1/ORM2, C4BPB, FTL, JUN, HP, HPX
B cell development	1.78	0.1210	HLA-DMA, HLA-DRB1, HLA-DRA, HLA-DMB
Aryl hydrocarbon receptor signaling	1.72	0.0692	HSPB1, GSTM5, GSTM1, MYC, RARB, JUN, NFE2L2, CYP1A2, GSTP1, NQO1, GSTA1
ERK/MAPK Signaling	1.56	0.0588	HSPB1, DUSP1, MYC, YWHAZ, PPP2CA, PRKAR2A, YWHAG, DUSP6, PLA2G2A, ITGB1, PPP1R3C, ETS1
Xenobiotic metabolism signaling	1.56	0.0508	GSTM5, CYP2B6, GCLC, UGT2B15, CYP1A2, GSTP1, GSTA1, HMOX1, GSTM1, FTL, PPP2CA, NFE2L2, FMO5, NQO1, UGT2B4
Eicosanoid signaling	1.56	0.0759	LTC4S, PTGER3, PRDX6, PLA2G2A, PLA2G16, AKR1C3
Complement system	1.56	0.1430	C4BPB, C6, C4BPA, C4B, C1QB
Pentose and glucuronate interconversions	1.56	0.0352	AKR1A1, UGT2B15, AKR7A3, AKR1C3, UGT2B4

Table 5 Relative mRNA levels of genes related to ribosome and xenobiotic/glutathione metabolism in the rat liver

Gene symbol	FDR-corrected P value	Control		BSEx
Gene symbol	FDR-corrected P value	Mean	SD	Mean	SD
Ribosome
Rpl10a	0.0018	1.00	0.06	0.82^b	0.05
Arbp	0.0056	1.00	0.13	0.86	0.24
Rpl15	0.0058	1.00	0.14	0.80	0.23
Rps16	0.0058	1.00	0.11	0.75^a	0.18
Rpl3	0.0068	1.00	0.12	1.07	0.20
Rps18	0.0086	1.00	0.06	1.00	0.17
Rps3	0.0096	1.00	0.05	1.34^a	0.27
Xenobiotic/glutathione metabolism
Cyp1a2	< 0.0001	1.00	0.32	2.43^b	0.66
Gstm1	< 0.0001	1.00	0.13	1.23	0.30
Gclc	0.0014	1.00	0.06	1.32^a	0.23
Gsta3	0.0018	1.00	0.13	1.58^a	0.43
Gstt3	0.0018	1.00	0.19	1.03	0.05
Gstp1	0.0287	1.00	0.14	0.94	0.30

^aP < 0.05,

^bP < 0.01 vs control group.

Table 6 Hepatoprotective effects of broccoli sprout extract on APAP-induced liver injury

Marker	Control		BSEx		APAP		APAP + BSEx
Marker	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Body weight (g)	188.45	10.38	190.90	11.36	172.39	9.91	183.63	8.87
Body weight gain after i.p (g)	3.88	1.77	3.59	1.53	-11.21^a	3.30	-1.05^b	2.84
Liver weight (g)	8.46	0.44	9.13	0.69	6.90^a	0.58	8.11^d	0.85
Liver/body	0.045	0.001	0.048	0.002	0.04^a	0.002	0.044^d	0.003
AST (IU/L)	71.41	6.99	59.98	8.46	5614.41^a	1997.83	70.91	15.74
ALT (IU/L)	12.51	0.57	9.81	1.84	1297.71^a	447.33	11.78	2.08
GST activity (U/g tissue)	61.78	4.95	77.89	4.62	51.90^c	16.85	93.19^b	16.55
TBARS (μmol/g tissue)	462.68	36.57	420.95	23.66	751.12^a	220.87	496.63	37.21
GSH (nmol/g tissue)	2.73	0.26	2.99	0.29	1.66^a	0.59	2.61	0.75

^aP < 0.05 vs Control, BSEx, APAP + BSEx;

^bP < 0.05 vs Control, BSEx, APAP;

^cP < 0.05 vs BSEx, APAP + BSEx;

^dP < 0.05 vs BSEx, APAPBSEx: Broccoli sprout extract; AST: Aspartate transaminase; ALT: Alanine transaminase; GSH: Hepatic glutathione; GST: Glutathione-S-transferase.

Table 7 Hepatoprotective effects of broccoli sprout extract on D-GalN-induced liver injury

Marker	Control		BSEx		D-GalN		D-GalN + BSEx
Marker	Mean	SD	Mean	SD	Mean	SD	Mean	SD
Body weight (g)	237.31	10.49	235.13	16.38	224.30	11.14	225.39	10.76
Body weight gain after i.p (g)	1.85	1.32	3.50	0.97	-7.74^a	2.42	-4.10^b	3.67
Liver weight (g)	10.38	0.32	11.16	1.25	7.40^a	0.60	8.32^b	1.33
Liver/body	0.044	0.001	0.048	0.002	0.032^a	0.001	0.036^b	0.005
AST (IU/L)	55.73	8.66	66.30	24.08	12465.63^a	3223.97	4820.05^b	3094.93
ALT (IU/L)	11.12	1.01	12.47	3.48	3936.46^a	777.52	1808.95^b	1014.04
GST activity (U/g tissue)	87.92	10.42	109.43	23.19	53.15^a	8.14	98.04	15.75
TBARS (μmol/g tissue)	418.96	33.06	442.34	41.10	543.81^c	45.35	495.42^d	54.46

^aP < 0.05 vs Control, BSEx, D-GalN + BSEx;

^bP < 0.05 vs Control, BSEx, D-GalN;

^cP < 0.05 vs Control, BSEx;

^dP < 0.05 vs Control. BSEx: Broccoli sprout extract; AST: Aspartate transaminase; ALT: Alanine transaminase; GSH: Hepatic glutathione; GST: Glutathione-S-transferase.

Citation: Yoshida K, Ushida Y, Ishijima T, Suganuma H, Inakuma T, Yajima N, Abe K, Nakai Y. Broccoli sprout extract induces detoxification-related gene expression and attenuates acute liver injury. World J Gastroenterol 2015; 21(35): 10091-10103
URL: https://www.wjgnet.com/1007-9327/full/v21/i35/10091.htm
DOI: https://dx.doi.org/10.3748/wjg.v21.i35.10091