The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract

Mansour, Dina F.; Abdallah, Heba M. I.; Ibrahim, Bassant M. M.; Hegazy, Rehab; Esmail, Reham Shehab El Nemr; Abdel‐Salam, Lubna O.

doi:10.31557/apjcp.2019.20.8.2551

Cited by 54 publications

(36 citation statements)

References 85 publications

(89 reference statements)

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“…This observation was supported by a decrease in mRNA levels of inflammatory factors such as IL-6 and IL-8. Further, S-[6]-gingerol was found to reduce both IL-1 β -induced COX2 upregulation and NF- κ B activity [ 63 ]. In another study, 6-gingerol was shown to forestall the increase in inflammatory markers such as myeloperoxidase, NO, and TNF-alpha in the brain, ovaries, and uterus of rats treated with chlorpyrifos.…”

Section: Discussionmentioning

confidence: 99%

6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity

Alsahli

Almatroodi

Almatroudi

et al. 2021

Mediators of Inflammation

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Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.

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Section: Discussionmentioning

confidence: 99%

6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity

Alsahli

Almatroodi

Almatroudi

et al. 2021

Mediators of Inflammation

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“…NDEA stimulates inflammatory cell infiltration (e.g. lymphocytes, neutrophils, eosinophils, and Kupffer cells), pro-inflammatory cytokines, including the IL-1 and IL-6 signaling pathway, as well as oxidative stress and proliferation in the liver, stomach and colon including cyclooxygenase (COX-2) expression in hepatic tissues ( Ding, Wu, Wei, Shu, & Peng, 2017 ; Duan et al, 2014 ; Hebels et al, 2009 ; Mansour et al, 2019 ). Thus, inflammation plays a critical role in carcinogen-induced cancers.…”

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

“…ROS are an important mechanism for tumor promotion and oxidative stress. As a consequence of NDEA-induced oxidative and nitrosative DNA damage ( Klaunig & Kamendulis, 2004 ; Unsal & Belge-Kurutas, 2017 ), inflammatory markers such as IL-1β and TNF-α are significantly elevated in liver, stomach and colon ( Mansour et al, 2019 ). The NDMA-mediated increase in NO production may also contribute to oxidative stress, a factor in the pathophysiology of numerous immune disorders.…”

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

“…Inhibition of Nrf2 stimulates oxidative stress, inflammation, circulating cytokines, and proliferation leading to intestinal carcinogenesis ( Cheung et al, 2014 ). NDEA stimulates inflammatory and oxidative stress markers via COX-2 upregulation, yet ginger extract demonstrated protective effects via Nrf2 activation to suppress oxidation and inflammation ( Mansour et al, 2019 ). AFB 1 upregulates Nrf2 signaling in response to oxidative stress, although expression of the SOD antioxidant is downregulated ( Wang et al, 2017 )().…”

Section: Mechanisms Of Pro-tumorigenic Activity By Carcinogensmentioning

confidence: 99%

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Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

138

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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“…Regarding liver tissue of groups treated with compound 4 or 5, the histopathology revealed vacuolar degeneration, most prominent being macro-vesicular in rats treated with compound 4 and less so in rats treated with compound 5. Renal tissue of groups treated with compound 4 and compound 5 showed prominent improvement within both glomeruli and tubules, glomeruli showed average cellularity, tubules showed patent lumina, being lined by low cuboidal epithelium, no vacuolar degeneration, no blood casts and no interstitial congestion [24,25].…”

Section: Histopathology Studymentioning

confidence: 99%

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

et al. 2021

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Diabetes is the most common metabolic disorder in both developing and non-developing countries, and a well-recognized global health problem. The WHO anticipates an increase in cases from 171 million in 2000 to 366 million by 2030. In the present study, we focus on the preparation of pyrimidine derivatives as potential antidiabetic and antimicrobial agents. Thein vivoeffect on total serum glucose concentration, cholesterol and antioxidant activity was assessed in adult male albino Wister rats and compared to the reference drug glimperide. Promising results were observed for compound 5. The histopathological study confirms that compound 5 results in significant activity with liver maintenance. The antimicrobial activities were evaluated against several bacterial strains such as Salmonella typhimurium ATCC 25566, Bacillus cereus, Escherichia coli NRRN 3008, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 6538and fungi such as Rhizopus oligosporus, Mucor miehei and Asperillus niger. Compounds 4 and 5 showed a good inhibition of the bacterial zone compared to the reference drug cephradine. Finally, we suggest protein targets for these drugs based on computational analysis, and infer their activities from their predicted modes of binding using molecular modeling. The molecular modeling for compounds 4 and 5 resulted in improved docking scores and hydrogen bonding. The docking studies are in good agreement with the in vitro and in vivo studies.

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The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract

Cited by 54 publications

References 85 publications

6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity

6-Gingerol, a Major Ingredient of Ginger Attenuates Diethylnitrosamine-Induced Liver Injury in Rats through the Modulation of Oxidative Stress and Anti-Inflammatory Activity

Carcinogenesis: Failure of resolution of inflammation?

Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

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