Thymoquinone prevents endoplasmic reticulum stress and mitochondria-induced apoptosis in a rat model of partial hepatic warm ischemia reperfusion

Autor: Ahlem Bouhlel, Hassen Ben Abdennebi, Anne Corlu, Roselyne Viel, Catherine Ribault, Saber Mannai, Ismail Ben Mosbah, Najet Hadj Abdallah
Přispěvatelé: Bioprédic International, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), H2P2 - Histo Pathologie Hight Precision (H2P2), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), UR12ES11, Tunisian Ministry of Higher Education and Scientific Research, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
MAPK/ERK pathway
Male
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Apoptosis
[SDV.CAN]Life Sciences [q-bio]/Cancer
Mitochondrion
Pharmacology
medicine.disease_cause
Protective Agents
p38 Mitogen-Activated Protein Kinases
Antioxidants
03 medical and health sciences
chemistry.chemical_compound
Ischemia
Benzoquinones
Medicine
Animals
Warm Ischemia
Phosphorylation
Rats
Wistar
Thymoquinone
business.industry
Tumor Necrosis Factor-alpha
Endoplasmic reticulum
General Medicine
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Endoplasmic Reticulum Stress
Mitochondria
Rats
Oxidative Stress
030104 developmental biology
chemistry
Liver
Reperfusion Injury
Immunology
Reperfusion
Unfolded protein response
business
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Oxidative stress
Ischemia reperfusion injury
Zdroj: Biomedicine and Pharmacotherapy
Biomedicine and Pharmacotherapy, Elsevier, 2017, 94, pp.964-973. ⟨10.1016/j.biopha.2017.08.018⟩
Biomedicine and Pharmacotherapy, 2017, 94, pp.964-973. ⟨10.1016/j.biopha.2017.08.018⟩
Biomedicine and Pharmacotherapy, Elsevier Masson, 2017, 94, pp.964-973. ⟨10.1016/j.biopha.2017.08.018⟩
ISSN: 0753-3322
1950-6007
DOI: 10.1016/j.biopha.2017.08.018⟩
Popis: International audience; This study was undertaken to evaluate the protective effect of thymoquinone (TQ), the bioactive compound of Nigella sativa seeds, against warm ischemia-reperfusion (I/R) injury in liver. Rats were given an oral administration of a vehicle solution (sham group) or TQ at the appropriate dose (10, 20, 30 and 40mg/kg) for ten days consecutively. Following, they were subjected to 60min of partial hepatic ischemia followed by 24h of reperfusion. .Transaminase activities, histopathological changes, TNFα and antioxidant parameters were evaluated. Also, endoplasmic reticulum (ER) stress, mitochondrial damage and apoptosis were studied. In addition, ERK and P38 phosphorylation was determined by Western blot technique. We found that TQ at 30mg/kg is the effective dose to protect rat liver against I/R injury. Moreover, 30mg/kg of TQ prevented histological damages, inflammation and oxidative stress. Interestingly, it decreased the expression of ER stress parameters including GRP78, CHOP and caspase-12. In parallel, it improved mitochondrial function and attenuated the expression of apoptotic parameters. Furthermore, TQ significantly enhanced ERK and P38 phosphorylation. In conclusion, we demonstrated the potential of TQ to protect the rat liver against I/R injury through the prevention of ER stress and mitochondrial dysfunction. These effects implicate the prevention of oxidative stress.
Databáze: OpenAIRE
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