Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice

Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 d...

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Veröffentlicht in:Human & experimental toxicology 2015-11, Vol.34 (11), p.1180-1194
Hauptverfasser: Saleh, IG, Ali, Z, Hammad, MA, Wilson, FD, Hamada, FM, Abd-Ellah, MF, Walker, LA, Khan, IA, Ashfaq, MK
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container_end_page 1194
container_issue 11
container_start_page 1180
container_title Human & experimental toxicology
container_volume 34
creator Saleh, IG
Ali, Z
Hammad, MA
Wilson, FD
Hamada, FM
Abd-Ellah, MF
Walker, LA
Khan, IA
Ashfaq, MK
description Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 days after a single intraperitoneal dose (6 mg/kg) of lipopolysaccharide (LPS). In this study, we aimed to study the effect of intrahepatic (IH) injection of mouse embryonic stem cells (MESCs) on the hepatotoxicity induced by EGCG/LPS in mice. Mice were administered EGCG/LPS and rested for 3 days. MESCs were obtained from American Type Culture Collection and cultured in vitro for 4 days. Stem cells were injected IH. Seven days later, a single dose of LPS (6 mg/kg) followed by daily doses of IG administration of EGCG were re-administered for 5 days. At the end of the experiment, blood samples were collected for analysis of biochemical parameters associated with liver. Results showed that the group of mice that were administered MESCs prior to EGCG/LPS showed lower levels of alanine amino transferase, alkaline phosphatase, and bilirubin, higher albumin/globulin ratio, and less remarkable histopathological lesions. Also, that group of mice showed less expression of oxidative stress biomarkers (oxidized low-density lipoprotein Ox.LDL and chemokine CXCL16), less expression of nuclear protein receptors (retinoic acid receptor and retinoid X receptor), and less expression of inflammatory biomarkers (tumor necrosis factor α and transforming growth factor β1) compared with other groups of mice that were not given MESCs. In conclusion, MESCs can ameliorate EGCG/LPS-induced hepatotoxicity in mice.
doi_str_mv 10.1177/0960327115572707
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experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2015-11</date><risdate>2015</risdate><volume>34</volume><issue>11</issue><spage>1180</spage><epage>1194</epage><pages>1180-1194</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 days after a single intraperitoneal dose (6 mg/kg) of lipopolysaccharide (LPS). In this study, we aimed to study the effect of intrahepatic (IH) injection of mouse embryonic stem cells (MESCs) on the hepatotoxicity induced by EGCG/LPS in mice. Mice were administered EGCG/LPS and rested for 3 days. MESCs were obtained from American Type Culture Collection and cultured in vitro for 4 days. Stem cells were injected IH. Seven days later, a single dose of LPS (6 mg/kg) followed by daily doses of IG administration of EGCG were re-administered for 5 days. At the end of the experiment, blood samples were collected for analysis of biochemical parameters associated with liver. Results showed that the group of mice that were administered MESCs prior to EGCG/LPS showed lower levels of alanine amino transferase, alkaline phosphatase, and bilirubin, higher albumin/globulin ratio, and less remarkable histopathological lesions. Also, that group of mice showed less expression of oxidative stress biomarkers (oxidized low-density lipoprotein Ox.LDL and chemokine CXCL16), less expression of nuclear protein receptors (retinoic acid receptor and retinoid X receptor), and less expression of inflammatory biomarkers (tumor necrosis factor α and transforming growth factor β1) compared with other groups of mice that were not given MESCs. In conclusion, MESCs can ameliorate EGCG/LPS-induced hepatotoxicity in mice.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>25701483</pmid><doi>10.1177/0960327115572707</doi><tpages>15</tpages></addata></record>
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subjects Alanine Transaminase - blood
Alkaline Phosphatase - blood
Amylases - blood
Animals
Aspartate Aminotransferases - blood
Catechin - analogs & derivatives
Cell culture
Chemical and Drug Induced Liver Injury - blood
Chemical and Drug Induced Liver Injury - metabolism
Chemical and Drug Induced Liver Injury - pathology
Chemical and Drug Induced Liver Injury - therapy
Chemokine CXCL16
Chemokine CXCL6 - metabolism
Drug therapy
Embryonic Stem Cells
Lipopolysaccharides
Lipoproteins, LDL - metabolism
Liver - drug effects
Liver - metabolism
Liver - pathology
Male
Mice
Oxidative Stress - drug effects
Rodents
Stem Cell Transplantation
Stem cells
Toxicity
Toxicology
Transforming Growth Factor beta1 - metabolism
Tumor Necrosis Factor-alpha - metabolism
title Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice
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