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

Bouhlel, Ahlem; Mosbah, Ismaïl Ben; Abdallah, Najet Hadj; Ribault, Catherine; Viel, Roselyne; Mannai, Saber; Corlu, Anne; Abdennebi, Hassen Ben

doi:10.1016/j.biopha.2017.08.018

Cited by 36 publications

(49 citation statements)

References 51 publications

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“…In contrast, rats pretreated with TQ before PH showed a reduction in liver injury and an improvement of the histopathological abnormalities. These findings consolidate previous reported works showing that TQ protects rat liver against IR injury . In line with the decrease of liver injury, we found that TQ promoted liver regeneration.…”

Section: Discussionsupporting

confidence: 93%

“…In our study, we demonstrated that the induction of ER stress parameters in response to PH under IR condition could be reduced by TQ pretreatment. Our data are in keeping with our previous findings showing that TQ reduces ER stress induced by warm liver IR in rat . However, how TQ protects ER from PH under I/R damage remains unclear; we presume that it could be related to the attenuation of oxidative stress.…”

Section: Discussionsupporting

confidence: 92%

“…It was previously reported that TQ has many pharmacological actions, including antioxidant and anti‐inflammatory effects against several hepatotoxic molecules . Moreover, it has been shown that TQ suppresses liver fibrosis and attenuates liver injury induced by ischaemia . Nevertheless, TQ effects have not been examined in an experimental model combining PH and I/R.…”

Section: Discussionmentioning

confidence: 99%

“…Rats were subjected to only laparotomy without occlusion of hepatic pedicle and PH. Group 2 (TQ group). Rats were orally pretreated with TQ (30 mg/kg) for ten consecutive days . Rat livers were then subjected to laparotomy without occlusion of hepatic pedicle and PH. Group 3 (PH group).…”

Section: Methodsmentioning

confidence: 99%

“…TQ has several biological activities, especially antioxidant and free radical scavenging capacity . Recently, it has been shown that TQ protects rat liver against I/R injury . However, its effect on liver subjected to resection under I/R is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Bouhlel

Béjaoui

Mosbah

et al. 2018

Clin Exp Pharma Physio

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Bouhlel

Béjaoui

Mosbah

et al. 2018

Clin Exp Pharma Physio

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The effects of thymoquinone and quercetin on the toxicity of acrylamide in rat glioma cells

Kaçar

Şahıntürk

Tomsuk

et al. 2022

J Biochem & Molecular Tox

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Acrylamide is a neurotoxic agent forming in foods. Thymoquinone and quercetin are plant‐derived antioxidants in various foods with known benefits. C6 cells are glioblastoma cells. In this study, we aimed at preventing acrylamide toxicity by thymoquinone and quercetin in the C6 cell line. In our study, first, toxic doses of acrylamide, nontoxic doses of thymoquinone and quercetin in C6 cells for 24 h were determined by MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) colorimetric test. After that, caspase 3/7 and annexin V tests were performed by flow cytometry to evaluate whether the apoptosis pathway was inducted. Furthermore, autophagy and oxidative stress were assessed by flow cytometry. The amount of Nrf2 (nuclear factor erythroid 2‐related factor 2) was determined by immunocytochemistry. The morphological examination was performed by microscopic analyses. As a result, 4 mM of acrylamide was determined to be used to induce toxicity in C6 cells. The nontoxic doses of thymoquinone and quercetin were respectively determined as 3.9 and 2.0 µM. Thymoquinone and quercetin not only reduced acrylamide‐induced apoptosis in annexin V and caspase 3/7 assays but also morphological deformations in microscopic examinations. In autophagy, it was revealed that acrylamide‐induced autophagy was decreased by quercetin and thymoquinone pretreatments. As for Nrf2 expression, it was observed that acrylamide increased Nrf2 expression, and thymoquinone and quercetin pretreatments increased it even further. In conclusion, in the study, acrylamide demonstrated a damaging effect on C6 glioblastoma cells, and thymoquinone and quercetin pretreatments exerted a protective effect against acrylamide‐induced damage in C6 cells.

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ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

Zhang

Piao

et al. 2023

Journal Cellular Physiology

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Hepatic ischemia-reperfusion (I/R) injury commonly occurs during liver surgery.Exosomes from adipose-derived stem cells (ADSCs-exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs-exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs-exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme-linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)-related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs-exo treatment.Moreover, ADSCs-exo treatment significantly downregulated tumor necrosis factorα, interleukin-1β (IL-1β), and IL-6 levels while upregulating IL-10 levels. Western blot analysis suggested that the protein expressions of GRP78, p-PERK, p-eIF2α, p-IRE1α, XBP1s, ATF-6, ATF-4, CHOP, p-JNK, cleaved-Caspase-3, cleaved Caspase-9, and cleaved Caspase-12 significantly decreased after ADSCs-exo treatment. RT-qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF-6, ATF-4, CHOP, JNK, Caspase-3, Caspase-9, and Caspase-12 markedly reduced after ADSCs-exo treatment. In conclusion, ADSCs-exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs-exo can be considered as a viable option for the treatment of hepatic I/R injury.

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

Cited by 36 publications

References 51 publications

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

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

The effects of thymoquinone and quercetin on the toxicity of acrylamide in rat glioma cells

ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation

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