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

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

Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of various organs. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENA in different organs namely, liver, stomach and colon and the potential p...

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Published in:Asian Pacific journal of cancer prevention : APJCP Vol. 20; no. 8; pp. 2551 - 2561
Main Authors: Mansour, Dina F, Abdallah, Heba M I, Ibrahim, Bassant M M, Hegazy, Rehab R, Esmail, Reham S E, Abdel-Salam, Lubna O
Format: Journal Article
Language:English
Published: Thailand West Asia Organization for Cancer Prevention 01-08-2019
Subjects:
Animals
Carcinogens - toxicity
Cell Proliferation - drug effects
Colon - drug effects
Colon - pathology
Diethylnitrosamine - toxicity
Inflammation - chemically induced
Inflammation - pathology
Inflammation - prevention & control
Liver - drug effects
Liver - pathology
Male
Oxidative Stress - drug effects
Plant Extracts - pharmacology
Rats
Rats, Wistar
Stomach - drug effects
Stomach - pathology
Zingiber officinale - chemistry
diethylnitrosamine
Inflammation
Proliferation
Ginger extract
oxidative stress
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Summary:Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of various organs. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENA in different organs namely, liver, stomach and colon and the potential protective effect of GE against these mechanisms. Methods: Adult male albino rats were assigned into four groups. A normal control group received the vehicle, another group was injected with a single necrogenic dose of DENA (200 mg/kg, i.p) on day 21. Two groups received oral GE (108 or 216 mg/kg) daily for 28 days. Sera, liver, stomach and colon were obtained 7 days after DENA injection. Serum aspartate transaminase and alanine transaminase were detected as well as reduced glutathione (GSH), malondialdehyde, nitric oxide metabolites, interleukin 1β, tumor necrosis factor (TNF-α), alpha-fetoprotein (AFP) and nuclear factorerythroid 2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemical examination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymes with significant increase in oxidation and inflammation biomarkers and AFP while decreased levels of Nrf2 in liver, stomach and colon were detected. Histologically, DENA showed degenerative changes in hepatocytes and inflammatory foci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatment improved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatory biomarkers compared to DENA-treated group. AFP was reduced by GE in both doses, while Nrf2 increased significantly. Histology and immunostaining of hepatic COX-2 were remarkably improved in GE-treated groups in a dose dependent manner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon via Nrf2 activation, whilst suppression of oxidation and inflammation.
ISSN:1513-7368
2476-762X
DOI:10.31557/APJCP.2019.20.8.2551