Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention

被引:13
作者
Bouhlel, Ahlem [1 ]
Bejaoui, Mohamed [1 ]
Ben Mosbah, Ismail [2 ,3 ]
Abdallah, Najet Hadj [1 ]
Ribault, Catherine [4 ]
Viel, Roselyne [5 ]
Hentati, Hassen [2 ]
Corlu, Anne [4 ]
Ben Abdennebi, Hassen [1 ]
机构
[1] Univ Monastir, Fac Pharm, Unite Biol & Anthropol Mol Appl Dev & Sante UR12E, Monastir, Tunisia
[2] Univ Paris Est, IMRB, Creteil, France
[3] Biopred Int, Rennes, France
[4] Univ Rennes, INRA, INSERM, Inst NUMECAN Nutr Metabolisms & Canc,UMR S1241,UM, Rennes, France
[5] Univ Rennes 1, US18, UMS Biosit 3480, Biogenouest, Plateforme H2P2, Rennes, France
关键词
apoptosis; endoplasmic reticulum stress; hepatectomy; ischaemia reperfusion injury; oxidative stress; thymoquinone; CARBON-TETRACHLORIDE; REGENERATION; ANTIOXIDANT; APOPTOSIS; INJURY; MODEL; HEPATOTOXICITY; MITOCHONDRIA; PRESERVATION; OBSTRUCTION;
D O I
10.1111/1440-1681.12961
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:943 / 951
页数:9
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