Document Type: Research Articles
Pharmacology Department, Medical Division, National Research Centre, 33 EL Bohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Giza, Egypt.
Department of Clinical Pharmacy and Pharmacy Practice,, Faculty of Pharmacy, Ahram Canadian University, Egypt.
Department of Pathology, Faculty of Medicine, Fayoum University, Egypt.
Department of Pathology, Faculty of Medicine, Cairo University, Egypt.
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.