Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats
Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Thirty-five 21-d-old female Spragu...
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| Veröffentlicht in: | The Journal of nutrition 2018-08, Vol.148 (8), p.1209-1216 |
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| creator | Gao, Xin Xiao, Zhuo-Hui Liu, Meng Zhang, Ni-Ya Khalil, Mahmoud Mohamed Gu, Chang-Qin Qi, De-Sheng Sun, Lv-Hui |
| description | Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects.
This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities.
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.
The consumption of ZEN decreased (P |
| doi_str_mv | 10.1093/jn/nxy114 |
| format | Article |
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This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities.
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.
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%.
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.]]></description><identifier>ISSN: 0022-3166</identifier><identifier>EISSN: 1541-6100</identifier><identifier>DOI: 10.1093/jn/nxy114</identifier><identifier>PMID: 30137478</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>AMP-Activated Protein Kinases - metabolism ; Animals ; Antioxidants - metabolism ; Antioxidants - pharmacology ; Antioxidants - therapeutic use ; ATP-Binding Cassette Transporters - metabolism ; Blood Proteins - metabolism ; Chemical and Drug Induced Liver Injury - metabolism ; Chemical and Drug Induced Liver Injury - pathology ; Chemical and Drug Induced Liver Injury - prevention & control ; Dietary Supplements ; Estrogen Receptor alpha - blood ; Female ; Glutathione Peroxidase - metabolism ; hepatotoxicity ; Hormones - blood ; Hydroxysteroid Dehydrogenases - metabolism ; Liver - drug effects ; Liver - enzymology ; Liver - pathology ; Malondialdehyde - blood ; Multidrug Resistance-Associated Proteins - metabolism ; Ovary - drug effects ; Ovary - pathology ; Phytotherapy ; rats ; Rats, Sprague-Dawley ; Reproduction - drug effects ; reproductive toxicity ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Silybum marianum - chemistry ; silymarin ; Silymarin - pharmacology ; Silymarin - therapeutic use ; Uterus - drug effects ; Uterus - pathology ; zearalenone ; Zearalenone - toxicity</subject><ispartof>The Journal of nutrition, 2018-08, Vol.148 (8), p.1209-1216</ispartof><rights>2018 American Society for Nutrition.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c364t-985999c3ae1bc11df9bdc8920e9df223b5329b57bf3c1b9853ac32245225109d3</citedby><cites>FETCH-LOGICAL-c364t-985999c3ae1bc11df9bdc8920e9df223b5329b57bf3c1b9853ac32245225109d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30137478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Xin</creatorcontrib><creatorcontrib>Xiao, Zhuo-Hui</creatorcontrib><creatorcontrib>Liu, Meng</creatorcontrib><creatorcontrib>Zhang, Ni-Ya</creatorcontrib><creatorcontrib>Khalil, Mahmoud Mohamed</creatorcontrib><creatorcontrib>Gu, Chang-Qin</creatorcontrib><creatorcontrib>Qi, De-Sheng</creatorcontrib><creatorcontrib>Sun, Lv-Hui</creatorcontrib><title>Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats</title><title>The Journal of nutrition</title><addtitle>J Nutr</addtitle><description><![CDATA[Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects.
This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities.
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.
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%.
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.]]></description><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Antioxidants - pharmacology</subject><subject>Antioxidants - therapeutic use</subject><subject>ATP-Binding Cassette Transporters - metabolism</subject><subject>Blood Proteins - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Chemical and Drug Induced Liver Injury - prevention & control</subject><subject>Dietary Supplements</subject><subject>Estrogen Receptor alpha - blood</subject><subject>Female</subject><subject>Glutathione Peroxidase - metabolism</subject><subject>hepatotoxicity</subject><subject>Hormones - blood</subject><subject>Hydroxysteroid Dehydrogenases - metabolism</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - pathology</subject><subject>Malondialdehyde - blood</subject><subject>Multidrug Resistance-Associated Proteins - metabolism</subject><subject>Ovary - drug effects</subject><subject>Ovary - pathology</subject><subject>Phytotherapy</subject><subject>rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reproduction - drug effects</subject><subject>reproductive toxicity</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</subject><subject>Silybum marianum - chemistry</subject><subject>silymarin</subject><subject>Silymarin - pharmacology</subject><subject>Silymarin - therapeutic use</subject><subject>Uterus - drug effects</subject><subject>Uterus - pathology</subject><subject>zearalenone</subject><subject>Zearalenone - toxicity</subject><issn>0022-3166</issn><issn>1541-6100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkDtPwzAUhS0EoqUw8AeQV4ZQP5K0HqvyaKVKSG1ZWCLHvpFcpU6w3ar59xiFMjHd4Xw6uudD6J6SJ0oEH-_s2J46StMLNKRZSpOcEnKJhoQwlnCa5wN04_2OEEJTMb1GA04on6ST6RB9PRsI0nV4Y-puL52xeHNo2xr2YIMMprF4VtdwNDKAx58gnazBNhaSpdUHBRovoJWhCc3JKBM6LK3Ga2hdE9NgjoC35yRWr2Xwt-iqkrWHu987Qh-vL9v5Ilm9vy3ns1WieJ6GREwzIYTiEmipKNWVKLWaCkZA6IoxXmaciTKblBVXtIw0l4ozlmaMZVGK5iP02Pcq13jvoCpaZ-LCrqCk-NFW7GzRa4vsQ8-2h3IP-o88e4oA7wGIHx8NuMIrAzbuNw5UKHRj_qn9BoOUfg0</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Gao, Xin</creator><creator>Xiao, Zhuo-Hui</creator><creator>Liu, Meng</creator><creator>Zhang, Ni-Ya</creator><creator>Khalil, Mahmoud Mohamed</creator><creator>Gu, Chang-Qin</creator><creator>Qi, De-Sheng</creator><creator>Sun, Lv-Hui</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201808</creationdate><title>Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats</title><author>Gao, Xin ; Xiao, Zhuo-Hui ; Liu, Meng ; Zhang, Ni-Ya ; Khalil, Mahmoud Mohamed ; Gu, Chang-Qin ; Qi, De-Sheng ; Sun, Lv-Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-985999c3ae1bc11df9bdc8920e9df223b5329b57bf3c1b9853ac32245225109d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>Antioxidants - pharmacology</topic><topic>Antioxidants - therapeutic use</topic><topic>ATP-Binding Cassette Transporters - metabolism</topic><topic>Blood Proteins - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Chemical and Drug Induced Liver Injury - prevention & control</topic><topic>Dietary Supplements</topic><topic>Estrogen Receptor alpha - blood</topic><topic>Female</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>hepatotoxicity</topic><topic>Hormones - blood</topic><topic>Hydroxysteroid Dehydrogenases - metabolism</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - pathology</topic><topic>Malondialdehyde - blood</topic><topic>Multidrug Resistance-Associated Proteins - metabolism</topic><topic>Ovary - drug effects</topic><topic>Ovary - pathology</topic><topic>Phytotherapy</topic><topic>rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reproduction - drug effects</topic><topic>reproductive toxicity</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Silybum marianum - chemistry</topic><topic>silymarin</topic><topic>Silymarin - pharmacology</topic><topic>Silymarin - therapeutic use</topic><topic>Uterus - drug effects</topic><topic>Uterus - pathology</topic><topic>zearalenone</topic><topic>Zearalenone - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Xin</creatorcontrib><creatorcontrib>Xiao, Zhuo-Hui</creatorcontrib><creatorcontrib>Liu, Meng</creatorcontrib><creatorcontrib>Zhang, Ni-Ya</creatorcontrib><creatorcontrib>Khalil, Mahmoud Mohamed</creatorcontrib><creatorcontrib>Gu, Chang-Qin</creatorcontrib><creatorcontrib>Qi, De-Sheng</creatorcontrib><creatorcontrib>Sun, Lv-Hui</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Journal of nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gao, Xin</au><au>Xiao, Zhuo-Hui</au><au>Liu, Meng</au><au>Zhang, Ni-Ya</au><au>Khalil, Mahmoud Mohamed</au><au>Gu, Chang-Qin</au><au>Qi, De-Sheng</au><au>Sun, Lv-Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats</atitle><jtitle>The Journal of nutrition</jtitle><addtitle>J Nutr</addtitle><date>2018-08</date><risdate>2018</risdate><volume>148</volume><issue>8</issue><spage>1209</spage><epage>1216</epage><pages>1209-1216</pages><issn>0022-3166</issn><eissn>1541-6100</eissn><abstract><![CDATA[Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects.
This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities.
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.
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%.
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.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30137478</pmid><doi>10.1093/jn/nxy114</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | AMP-Activated Protein Kinases - metabolism Animals Antioxidants - metabolism Antioxidants - pharmacology Antioxidants - therapeutic use ATP-Binding Cassette Transporters - metabolism Blood Proteins - metabolism Chemical and Drug Induced Liver Injury - metabolism Chemical and Drug Induced Liver Injury - pathology Chemical and Drug Induced Liver Injury - prevention & control Dietary Supplements Estrogen Receptor alpha - blood Female Glutathione Peroxidase - metabolism hepatotoxicity Hormones - blood Hydroxysteroid Dehydrogenases - metabolism Liver - drug effects Liver - enzymology Liver - pathology Malondialdehyde - blood Multidrug Resistance-Associated Proteins - metabolism Ovary - drug effects Ovary - pathology Phytotherapy rats Rats, Sprague-Dawley Reproduction - drug effects reproductive toxicity Ribosomal Protein S6 Kinases, 70-kDa - metabolism Silybum marianum - chemistry silymarin Silymarin - pharmacology Silymarin - therapeutic use Uterus - drug effects Uterus - pathology zearalenone Zearalenone - toxicity |
| title | Dietary Silymarin Supplementation Alleviates Zearalenone-Induced Hepatotoxicity and Reproductive Toxicity in Rats |
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