Journal Article

Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats

Xin Gao, Zhuo-Hui Xiao, Meng Liu, Ni-Ya Zhang, Mahmoud Mohamed Khalil, Chang-Qin Gu, De-Sheng Qi and Lv-Hui Sun

in The Journal of Nutrition

Published on behalf of American Society for Nutrition

Volume 148, issue 8, pages 1209-1216
Published in print August 2018 | ISSN: 0022-3166
Published online August 2018 | e-ISSN: 1541-6100 | DOI: https://dx.doi.org/10.1093/jn/nxy114
Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats

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  • Medicine and Health
  • Dietetics and Nutrition
  • Biochemistry
  • Food Microbiology
  • Gut Microbiology

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Abstract

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) 17β-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 3β-hydroxysteroid dehydrogenase (HSD3B) by 43.0–121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-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.

Keywords: silymarin; zearalenone; hepatotoxicity; reproductive toxicity; rats

Journal Article.  5133 words.  Illustrated.

Subjects: Medicine and Health ; Dietetics and Nutrition ; Biochemistry ; Food Microbiology ; Gut Microbiology

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