PMID- 30137478
OWN - NLM
STAT- MEDLINE
DCOM- 20190507
LR  - 20231213
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Linking)
VI  - 148
IP  - 8
DP  - 2018 Aug 1
TI  - Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity 
      and Reproductive Toxicity in Rats.
PG  - 1209-1216
LID - 10.1093/jn/nxy114 [doi]
AB  - BACKGROUND: Zearalenone (ZEN) can cause serious defects in development and 
      reproduction in humans and animals. Silymarin shows antioxidant and estrogenic 
      effects. OBJECTIVE: This study was conducted to determine if silymarin can 
      antagonize ZEN-induced hepatic and reproductive toxicities. METHODS: Thirty-five 
      21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) 
      or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg 
      silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 
      6 for biochemistry, hormone, and redox status and selected gene and protein 
      assays. RESULTS: The consumption of ZEN decreased (P < 0.05) the final body 
      weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate 
      aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) 
      total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused 
      reproductive toxicity, including decreased (P < 0.05) 17beta-estradiol and increased 
      (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and 
      induced histopathologic alterations in the liver, ovaries, and uterus. 
      Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by 
      silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin 
      supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in 
      hepatic glutathione peroxidase activity, total antioxidant capacity, and 
      malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation 
      at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 
      (p-RPS6KB1) and 3beta-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but 
      downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 
      3alpha-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 
      11.2-40.6%. In addition, silymarin supplementation at all doses elevated 
      (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 
      (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 
      10.7-63.2%. CONCLUSION: Dietary silymarin supplementation at 100, 200, and 500 
      mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, 
      potentially through improvement in the antioxidant capacity and regulation in the 
      genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC 
      transporters in the tissues.
FAU - Gao, Xin
AU  - Gao X
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Xiao, Zhuo-Hui
AU  - Xiao ZH
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Liu, Meng
AU  - Liu M
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Zhang, Ni-Ya
AU  - Zhang NY
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Khalil, Mahmoud Mohamed
AU  - Khalil MM
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Gu, Chang-Qin
AU  - Gu CQ
AD  - Department of Veterinary Pathology, College of Veterinary Medicine, Huazhong 
      Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Qi, De-Sheng
AU  - Qi DS
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
FAU - Sun, Lv-Hui
AU  - Sun LH
AD  - Department of Animal Nutrition and Feed Science, College of Animal Science and 
      Technology, Huazhong Agricultural University, Wuhan, China.
AD  - Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abcc5 protein, rat)
RN  - 0 (Antioxidants)
RN  - 0 (Blood Proteins)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Hormones)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Silymarin)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 5W827M159J (Zearalenone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Antioxidants/metabolism/pharmacology/*therapeutic use
MH  - Blood Proteins/metabolism
MH  - Chemical and Drug Induced Liver Injury/metabolism/pathology/*prevention & control
MH  - Dietary Supplements
MH  - Estrogen Receptor alpha/blood
MH  - Female
MH  - Glutathione Peroxidase/metabolism
MH  - Hormones/blood
MH  - Hydroxysteroid Dehydrogenases/metabolism
MH  - Liver/*drug effects/enzymology/pathology
MH  - Malondialdehyde/blood
MH  - Silybum marianum/*chemistry
MH  - Multidrug Resistance-Associated Proteins/metabolism
MH  - Ovary/drug effects/pathology
MH  - Phytotherapy
MH  - Rats, Sprague-Dawley
MH  - Reproduction/*drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Silymarin/pharmacology/*therapeutic use
MH  - Uterus/drug effects/pathology
MH  - Zearalenone/*toxicity
EDAT- 2018/08/24 06:00
MHDA- 2019/05/08 06:00
CRDT- 2018/08/24 06:00
PHST- 2018/01/25 00:00 [received]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/08/24 06:00 [entrez]
PHST- 2018/08/24 06:00 [pubmed]
PHST- 2019/05/08 06:00 [medline]
AID - S0022-3166(22)16386-8 [pii]
AID - 10.1093/jn/nxy114 [doi]
PST - ppublish
SO  - J Nutr. 2018 Aug 1;148(8):1209-1216. doi: 10.1093/jn/nxy114.