Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

El-Khouly, Dalia; El-Bakly, Wesam M.; Awad, Azza S.; El‐Mesallamy, Hala O.; El‐Demerdash, Ebtehal

doi:10.1016/j.tox.2012.09.001

Cited by 71 publications

(44 citation statements)

References 50 publications

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“…6 Within the present study, we found signs of oxidative stress (identified by Sod1) and DNA stress (p21 positivity) locally in lung, thus confirming the induction of oxidative stress by bleomycin in accordance with previous descriptions. 2,3 Interestingly, Sod1 was normalized at 2 and 3w, despite continuous bleomycin administrations. This may indicate the presence of other ROS-neutralizing enzymes, development of tolerance, or depletion of Sod1 protein.…”

Section: Discussionmentioning

confidence: 97%

“…Bleomycin exerts it's effect through generation of reactive oxygen species (ROS), which results in oxidative stress in lung also after systemic administration. 2,3 In addition, the oxidative effects of bleomycin in vitro have also been well described. 4,5 In contrast to intratracheal administration of bleomycin, repeated subcutaneous administrations result in a systemic exposure, and cause distal fibrosis that develops in parallel with mild inflammation.…”

mentioning

confidence: 99%

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ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling

Andersson-Sjöland

Karlsson

Rydell‐Törmänen

2016

Laboratory Investigation

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Pulmonary fibrosis is a grave diagnosis with insidious progression, generally considered as a consequence of aberrant epithelial wound healing and excessive scarring. This process is commonly modeled in animals by local bleomycin administration, resulting in peribronchial inflammation and subsequent fibrosis. We have previously described initiation and early development of distal pulmonary fibrosis following repeated subcutaneous bleomycin injections (systemic administration). The aim of this study was to identify mechanisms for the development of pulmonary fibrosis, which we hypothesize is related to endothelial stress and activation. Bleomycin was administered subcutaneously 3 times/ week during 0.33-4w, and parenchymal alterations were studied. In addition, we used microvascular endothelial cells to investigate effects of bleomycin in vitro. Our results confirmed that systemic administration of bleomycin exerts oxidative stress indicated by an increase in Sod1 at 0.33, 1, and 4w (Po0.05). Endothelial cells were activated (increased CD106 expression) from 1w and onwards (Po0.05), and p21 expression was increased 2-3 times throughout the study (Po0.05) as were the number of β-catenin-positive nuclei (Po0.001). Wnt3a was increased at 0.33, 1, and 4w (Po0.01) and Wnt5a from 1w and onwards (Po0.001). The present study suggests that bleomycin-induced reactive oxygen species (ROS) causes DNA stress affecting the endothelial niche, initiating repair processes including Wnt signaling. The repeated systemic administrations disrupt a normally fine-tuned balance in the Wnt signaling. In addition, pericyte differentiation was affected, which may have significant effects on fibrosis due to their ability to differentiate into myofibroblasts. We conclude that the endothelial niche may have an important role in the development of pulmonary fibrosis and warrants further investigations.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling

Andersson-Sjöland

Karlsson

Rydell‐Törmänen

2016

Laboratory Investigation

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“…Hydroxyproline measurement was also performed to evaluate fibrosis in the same study and was found to be markedly lower in thymoquinone treatment group. In addition, histopathological examination has verified the anti-fibrotic effect [20] . Ghazwani et al [20] evaluated the effect of thymoquinone on fibrosis mechanism in-vivo and in-vitro in liver cell line (hepatic stellate cell, or HSCs) and thymoquinone was found to have a protective effect in liver damage-induced mice by CCl4 when compared to controls.…”

Section: Discussionmentioning

confidence: 84%

“…In addition, histopathological examination has verified the anti-fibrotic effect [20] . Ghazwani et al [20] evaluated the effect of thymoquinone on fibrosis mechanism in-vivo and in-vitro in liver cell line (hepatic stellate cell, or HSCs) and thymoquinone was found to have a protective effect in liver damage-induced mice by CCl4 when compared to controls. There were similar results in in vitro studies performed with HSCs and LX2 cells, in which α-smooth muscle actin (α-SMA), COL1A1, COL3A1, IL6, MCP-1 gene expression was shown to down-regulate [21] .…”

Section: Discussionmentioning

confidence: 84%

“…In another study [20] where bleomycin induced rats were used as pulmonary fibrosis model, the effect of thymoquinone on the severity of oxidative stress and anti-inflammatory response was evaluated. While bleomycin significantly increased lung tissue weight, lactate dehydrogenase, total leukocyte and total protein amount, all these effects were meliorated in the group treated with thymoquinone.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Thymoquinone on BEAS-2B Cell Viability and TGF-β1 Release

et al. 2017

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<p>Thymoquinone, one of the essential oil in the structure of cumin, is used for alternative therapy for many diseases from past to present. It was shown to have anti-carcinogenic and anti-inflammatory effects, as well as positive effects on fibrosis. However, there is no study on the effect of thymoquinone on cancer and fibrosis mechanism in bronchial epithelium cell line BEAS-2B. In our study, the effect of thymoquinone on cell viability and transforming growth factor-beta 1 (TGF-β1) level, which has an important role in the regulation of many biological processes including cancer and fibrosis-associated signal transduction, was evaluated. BEAS-2B cells were exposed to thymoquinone at 0–80 μmol/L concentrations for 24-, 48- and 72-hour durations. Cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. TGF-β1 level was determined with enzyme-linked immunosorbent assay (ELISA) method from the collected supernatant. Cell viability was found to be increased at all concentrations and durations (10–80 μmol/L; 24, 48 and 72 h) according to the control group (0 μmol/L; thymoquinone in ethanol) (p < 0.0001). Moreover, thymoquinone was found to increase the level of TGF-β1 only at 80 μmol/L concentration and 24-hour exposure period (0 μmol/L, 53.41 ± 18.44 pgr/ml TGF-β1; 80 μmol/L, 174.5 ± 80.03 pgr/ml TGF-β1). As a result, thymoquinone was found to increase cell proliferation and encourage TGF-β1 release.</p>

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Therapeutic perspective of thymoquinone: A mechanistic treatise

Butt¹,

Imran

et al. 2021

Food Science & Nutrition

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The higher utilization of fruits and vegetables is well known to cure human maladies due to the presence of bioactive components. Among these compounds, thymoquinone, a monoterpene and significant constituent in the essential oil of Nigella sativa L., has attained attention by the researchers due to their pharmacologies perspectives such as prevention from cancer, antidiabetic and antiobesity, prevention from oxidative stress and cardioprotective disorder. Thymoquinone has been found to work as anticancer agent against different human and animal cancer stages including propagation, migration, and invasion. Thymoquinone as phytochemical also downregulated the Rac1 expression, mediated the miR‐34a upregulation, and increased the levels of miR‐34a through p53, as well as also regulated the pro‐ and antiapoptotic genes and decreased the phosphorylation of NF‐κB and IKKα/β. In addition, thymoquinone also lowered the metastasis and ERK1/2 and PI3K activities. The present review article has been piled by adapting narrative review method and highlights the diverse aspects of thymoquinone such as hepatoprotective, anti‐inflammatory, and antiaging through various pathways, and further utilization of this compound in diet has been proven effective against different types of cancers.

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Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

Cited by 71 publications

References 50 publications

ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling

ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling

The Effect of Thymoquinone on BEAS-2B Cell Viability and TGF-β1 Release

Therapeutic perspective of thymoquinone: A mechanistic treatise

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