title: Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice.
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.
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA Department of Pharmacology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: I G
authors.initials: IG
authors.lastname: Saleh
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ali
authors.affiliation: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Hammad
authors.affiliation: Mississippi Veterinary Research and Diagnostic Laboratory, College of Veterinary Medicine, Mississippi State University, Pearl, MS, USA.
authors.forename: F D
authors.initials: FD
authors.lastname: Wilson
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: F M
authors.initials: FM
authors.lastname: Hamada
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: M F
authors.initials: MF
authors.lastname: Abd-Ellah
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA Department of Pharmacology, School of Pharmacy, University of Mississippi, Oxford, MS, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA Department of Pharmacognosy, School of Pharmacy, University of Mississippi, Oxford, MS, USA Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: I A
authors.initials: IA
authors.lastname: Khan
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA mkashfaq@olemiss.edu.
authors.forename: M K
authors.initials: MK
authors.lastname: Ashfaq
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000681:Amylases / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002392:Catechin / Q000031:analogs & derivatives*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism; D053595:Embryonic Stem Cells; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D033581:Stem Cell Transplantation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D002392:Catechin; C045651:epigallocatechin gallate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000681:Amylases
keywords: Green tea; epigallocatechin-3-gallate; hepatotoxicity; lipopolysaccharide; mice; stem cells