Effectiveness of thymoquinone, zeolite, and platelet-rich plasma in model of corrosive oesophagitis induced in rats

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Abstract

Purpose

The effectiveness of platelet-rich plasma (PRP), thymoquinone, and zeolite in corrosive esophageal burns was investigated in a rat model.

Methods

Four groups were comprised as containing 10 rats in each group. For group I, oesophagitis was induced and no other procedure was performed (control group). For group II, oesophagitis was induced and thymoquinone was administered for 1 week via oral gavage once a day (thymoquinone group). For group III, oesophagitis was induced for 1 week via oral gavage once a day (PRP group). For group IV, oesophagitis was induced and zeolite was administered for 1 week via oral gavage once a day (zeolite group). On the 10th day, the rats were sacrificed under anaesthesia and venous blood sampling was performed from the vena portae. The oesophaguses were totally excised. Biochemically, interleukin (IL)-1B, IL-6, TNF-α, and MCP-1 were examined from venous blood. Inflammation score was evaluated histopathologically in oesophageal tissue that was collected.

Results

There was a statistically significant difference among groups in terms of IL-1, IL-6, MCP levels, compared to the control group; median IL-1, IL-6, MCP levels of thymoquinone, PRP, and zeolite groups were statistically significantly lower. There was a statistically significant difference among groups in terms of inflammation scores, compared to group I; median inflammation scores of groups II, III and IV were statistically significantly lower thymoquinone.

Conclusion

PRP, and zeolite exhibited positive effect on recovery in oesophagitis by reducing inflammation in the involved segment.

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Most cited references 29

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Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

Rany Salem (2005)

A larger number of medicinal plants and their purified constituents have been shown beneficial therapeutic potentials. Seeds of Nigella sativa, a dicotyledon of the Ranunculaceae family, have been employed for thousands of years as a spice and food preservative. The oil and seed constituents, in particular thymoquinine (TQ), have shown potential medicinal properties in traditional medicine. In view of the recent literature, this article lists and discusses different immunomodulatory and immunotherapeutic potentials for the crude oil of N. sativa seeds and its active ingredients. The published findings provide clear evidence that both the oil and its active ingredients, in particular TQ, possess reproducible anti-oxidant effects through enhancing the oxidant scavenger system, which as a consequence lead to antitoxic effects induced by several insults. The oil and TQ have shown also potent anti-inflammatory effects on several inflammation-based models including experimental encephalomyelitis, colitis, peritonitis, oedama, and arthritis through suppression of the inflammatory mediators prostaglandins and leukotriens. The oil and certain active ingredients showed beneficial immunomodulatory properties, augmenting the T cell- and natural killer cell-mediated immune responses. Most importantly, both the oil and its active ingredients expressed anti-microbial and anti-tumor properties toward different microbes and cancers. Coupling these beneficial effects with its use in folk medicine, N. sativa seed is a promising source for active ingredients that would be with potential therapeutic modalities in different clinical settings. The efficacy of the active ingredients, however, should be measured by the nature of the disease. Given their potent immunomodulatory effects, further studies are urgently required to explore bystander effects of TQ on the professional antigen presenting cells, including macrophages and dendritic cells, as well as its modulatory effects upon Th1- and Th2-mediated inflammatory immune diseases. Ultimately, results emerging from such studies will substantially improve the immunotherapeutic application of TQ in clinical settings.

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Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways.

Gautam Sethi, Xiufeng Pang, Mingyao Liu … (2008)

Thymoquinone, a component derived from the medial plant Nigella sativa, has been used for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on cell proliferation of many cancer cell lines and hormone-refractory prostate cancer by suppressing androgen receptor and E2F-1. Whether thymoquinone inhibits tumor angiogenesis, the critical step of tumor growth and metastasis, is still unknown. In this study, we found that thymoquinone effectively inhibited human umbilical vein endothelial cell migration, invasion, and tube formation. Thymoquinone inhibited cell proliferation and suppressed the activation of AKT and extracellular signal-regulated kinase. Thymoquinone blocked angiogenesis in vitro and in vivo, prevented tumor angiogenesis in a xenograft human prostate cancer (PC3) model in mouse, and inhibited human prostate tumor growth at low dosage with almost no chemotoxic side effects. Furthermore, we observed that endothelial cells were more sensitive to thymoquinone-induced cell apoptosis, cell proliferation, and migration inhibition compared with PC3 cancer cells. Thymoquinone inhibited vascular endothelial growth factor-induced extracellular signal-regulated kinase activation but showed no inhibitory effects on vascular endothelial growth factor receptor 2 activation. Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth and could be used as a potential drug candidate for cancer therapy.

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Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells.

Martin H. Roepke, Antje Diestel, Khuloud Bajbouj … (2007)

We have recently shown that thymoquinone (TQ) is an antineoplastic drug that induces p53-dependent apoptosis in human colon cancer cells. This study evaluated the antiproliferative and pro-apoptotic effects of TQ in two human osteosarcoma cell lines with different p53 mutation status. TQ decreased cell survival dose-dependently and, more significantly, in p53-null MG63 cells (IC(50) = 17 muM) than in p53-mutant MNNG/HOS cells (IC(50) = 38 muM). Cell viability was reduced more selectively in MG63 tumor cells than in normal human osteoblasts. Flow cytometric analysis showed that TQ induced a much greater increase in the PreG(1) (apoptotic) cell population, but no cell cycle arrest in MG63. G(2)/M arrest in MNNG/HOS cells was associated with p21(WAF1) upregulation. Using three DNA damage assays, TQ was confirmed to result in a significantly greater extent of apoptosis in p53 null MG63 cells. Although the Bax/Bcl-2 ratios were not differentially modulated in both cell lines, the mitochondrial pathway appeared to be involved in TQ-induced apoptosis in MG63 by showing the cleavage of caspases-9 and -3. Oxidative stress and mitochondrial O(2)(*-) generation in isolated rat mitochondria were enhanced by TQ as measured by the dose-dependent reduction in aconitase enzyme activity and Amplex Red oxidation respectively. TQ-induced oxidative damage, reflected by an increase in gamma-H2AX foci and increased protein expression levels of gamma-H2AX and the DNA repair enzyme, NBS1, was more pronounced in MNNG/HOS than in MG63. We suggest that the resistance of MNNG/HOS cells to drug-induced apoptosis is caused by the up-regulation of p21(WAF1) by the mutant p53 (transcriptional activity was shown by p53 siRNA treatment) which induces cell cycle arrest and allows to repair DNA damage. Collectively, these findings show that TQ induces p53-independent apoptosis in human osteosarcoma cells. As the loss of p53 function is frequently observed in osteosarcoma patients, our data suggest the potential clinical usefulness of TQ for the treatment of these malignancies.

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Author and article information

Journal

Journal ID (nlm-ta): Ann Surg Treat Res

Journal ID (iso-abbrev): Ann Surg Treat Res

Journal ID (publisher-id): ASTR

Title: Annals of Surgical Treatment and Research

Publisher: The Korean Surgical Society

ISSN (Print): 2288-6575

ISSN (Electronic): 2288-6796

Publication date (Print): June 2017

Publication date (Electronic): 29 May 2017

Volume: 92

Issue: 6

Pages: 396-401

Affiliations

Department of General Surgery, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey.

[1 ]Department of Biochemistry, Istanbul University, Istanbul, Turkey.

Author notes

Corresponding Author: Gökhan Karaca. Kırıkkale Üniversitesi Tıp Fakültesi Araştırma ve Uygulama Hastanesi Kırıkkale Üniversitesi Kampüsü Ankara Yolu 7.Km.71450 Yahşihan/Kirikkale/Turkey. Tel: +90-318-4444071, Fax: +90-318-4444071, gokhankaracaa@ 123456yahoo.com

Article

DOI: 10.4174/astr.2017.92.6.396

PMC ID: 5453871

SO-VID: 2271d8a9-e6c9-4d8b-9570-d1b8d2fb91ef

License:

Annals of Surgical Treatment and Research is an Open Access Journal. All articles are distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 16 November 2016

Date revision received : 20 January 2017

Date accepted : 23 January 2017

Funding

Funded by: Zhejiang Provincial Natural Science Foundation of China, CrossRef http://dx.doi.org/10.13039/501100004731;

Effectiveness of thymoquinone, zeolite, and platelet-rich plasma in model of corrosive oesophagitis induced in rats

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Most cited references 29

Immunomodulatory and therapeutic properties of the Nigella sativa L. seed.

Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways.

Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells.

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