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Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention
Authors:Ahlem Bouhlel  Mohamed Bejaoui  Ismail Ben Mosbah  Najet Hadj Abdallah  Catherine Ribault  Roselyne Viel  Hassen Hentati  Anne Corlu  Hassen Ben Abdennebi
Affiliation:1. Faculté de Pharmacie, Unité de Biologie et Anthropologie Moléculaire Appliquées au Développement et à la Santé (UR12ES11), Université de Monastir, Monastir, Tunisia;2. Institut Mondor Recherche Biomédicale (IMRB), Université Paris‐Est, Créteil, France;3. Biopredic International, Rennes, France;4. INSERM, INRA, Université Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), UMR_S1241, UMR_A 1341, Rennes, France;5. Université de Rennes 1, US18, UMS 3480 Biosit, Biogenouest, Plateforme H2P2, Rennes, France
Abstract:Ischaemia reperfusion (I/R) is associated with liver injury and impaired regeneration during partial hepatectomy (PH). The aim of this study was to investigate the effect of thymoquinone (TQ), the active compound of essential oil obtained from Nigella sativa seeds, on rat liver after PH. Male Wistar rats were divided equally into four groups (n = 6) receiving an oral administration of either vehicle solution (sham and PH groups) or TQ at 30 mg/kg (TQ and TQ + PH groups) for 10 consecutive days. Then, rats underwent PH (70%) with 60 minutes of ischaemia followed by 24 hours of reperfusion (PH and TQ + PH groups). Alanine aminotransferase (ALT) activity and histopathological damage were determined. Also, antioxidant parameters, liver regeneration index, hepatic adenosine triphosphate (ATP) content, endoplasmic reticulum (ER) stress and apoptosis were assessed. In response to PH under I/R, liver damage was significantly alleviated by TQ treatment as evidenced by the decrease in ALT activity (P < .01) and histological findings (P < .001). In parallel, TQ preconditioning increased hepatic antioxidant capacities. Moreover, TQ improved mitochondrial function (ATP, P < .05), attenuated ER stress parameters and repressed the expression of apoptotic effectors. Taken together, our results suggest that TQ preconditioning could be an effective strategy to reduce liver injury after PH under I/R. The protective effects were mediated by the increase of antioxidant capacities and the decrease of ER stress and apoptosis.
Keywords:apoptosis  endoplasmic reticulum stress  hepatectomy  ischaemia reperfusion injury  oxidative stress  thymoquinone
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