title: Pomegranate protects liver against cecal ligation and puncture-induced oxidative stress and inflammation in rats through TLR4/NF-κB pathway inhibition.
abstract: Acute liver injury secondary to sepsis is a major challenge in intensive care unit. This study was designed to investigate potential protective effects of pomegranate against sepsis-induced acute liver injury in rats and possible underlying mechanisms. Pomegranate was orally given (800mg/kg/day) for two weeks before sepsis induction by cecal ligation and puncture (CLP). Pomegranate improved survival and attenuated liver inflammatory response, likely related to downregulation of mRNA expression of toll like recptor-4, reduced nuclear translocation and DNA binding activity of proinflammatory transcription factor NF-κB subunit p65, decreased mRNA and protein expression of tumor necrosis factor-alpha and reduction in myeloperoxidase activity and mRNA expression. Pomegranate also decreased CLP-induced oxidative stress as reflected by decreased malondialdehyde content, and increased reduced glutathione level and superoxide dismutase activity. These results confirm the antiinflammatory and antioxidant effects of pomegranate in CLP-induced acute liver injury mediated through inhibiting TLR4/NF-κB pathway, lipid peroxidation and neutrophil infiltration.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: mirhan_makled@hotmail.com.
authors.forename: Mirhan N
authors.initials: MN
authors.lastname: Makled
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: El-Awady
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Rania R
authors.initials: RR
authors.lastname: Abdelaziz
authors.affiliation: Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Nadia
authors.initials: N
authors.lastname: Atwan
authors.affiliation: Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Emma T
authors.initials: ET
authors.lastname: Guns
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Nariman M
authors.initials: NM
authors.lastname: Gameil
authors.affiliation: Department of Nephrology and Urology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Ahmed B
authors.initials: AB
authors.lastname: Shehab El-Din
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Elsayed M
authors.initials: EM
authors.lastname: Ammar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002432:Cecum / Q000601:surgery; D007249:Inflammation / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000378:metabolism / Q000502:physiology; D029561:Lythraceae; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011677:Punctures; D051381:Rats
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D010936:Plant Extracts; D020011:Protective Agents
keywords: Acute liver injury; Cecal ligation and puncture; Nuclear factor-κB; Pomegranate; Toll-like receptor-4