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Biomed Pharmacother. 2017 Oct;94:964-973. doi: 10.1016/j.biopha.2017.08.018. Epub 2017 Aug 12.

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

Author information

1
Unité de Biologie et Anthropologie Moléculaires Appliquées au Développement et à la Santé (UR12ES11), Faculté de Pharmacie, Université de Monastir, Monastir, Tunisia.
2
Institut Mondor Recherche Biomédicale (IMRB), Université Paris-Est, Créteil, France; Biopredic International, Rennes, France.
3
Inserm, UMR991, Foie, Métabolismes et Cancer, Hôpital Pontchaillou, Université de Rennes 1, Rennes, France.
4
Plateforme Histopathologie Haute Précision (H²P²), Biosit : biologie, santé, innovation technologique, SFR UMS CNRS 3480 - INSERM 018, Université de Rennes, France.
5
Department of general Surgery, Hospital Mahmoud El Matri, Faculty of Medicine of Tunis, University of Tunis El Manar, 2083 Ariana, Tunisia.
6
Unité de Biologie et Anthropologie Moléculaires Appliquées au Développement et à la Santé (UR12ES11), Faculté de Pharmacie, Université de Monastir, Monastir, Tunisia. Electronic address: hbenabdennebi@yahoo.fr.

Abstract

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.

KEYWORDS:

Apoptosis; Endoplasmic reticulum stress; Ischemia reperfusion injury; Oxidative stress; Thymoquinone

PMID:
28810534
DOI:
10.1016/j.biopha.2017.08.018
[Indexed for MEDLINE]

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