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Asian Pac J Cancer Prev. 2019 Aug 1;20(8):2551-2561. doi: 10.31557/APJCP.2019.20.8.2551.

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

Author information

1
Pharmacology Department, Medical Division, National Research Centre, 33 EL Bohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Giza, Egypt. Email: dinaf.mansour@gmail.com
2
Department of Clinical Pharmacy and Pharmacy Practice,, Faculty of Pharmacy, Ahram Canadian University, Egypt.
3
Department of Pathology, Faculty of Medicine, Fayoum University, Egypt.
4
Department of Pathology, Faculty of Medicine, Cairo University, Egypt.

Abstract

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.

KEYWORDS:

Ginger extract; Inflammation; Proliferation; diethylnitrosamine; oxidative stress

PMID:
31450931
DOI:
10.31557/APJCP.2019.20.8.2551
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