TY - JOUR ID - 88710 TI - The Carcinogenic Agent Diethylnitrosamine Induces Early Oxidative Stress, Inflammation and Proliferation in Rat Liver, Stomach and Colon: Protective Effect of Ginger Extract JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Mansour, Dina F AU - Abdallah, Heba M I AU - Ibrahim, Bassant M M AU - Hegazy, Rehab R AU - Esmail, Reham S E AU - Abdel-Salam, Lubna O AD - Pharmacology Department, Medical Division, National Research Centre, 33 EL Bohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Giza, Egypt. AD - Department of Pathology, Faculty of Medicine, Fayoum University, Egypt. AD - Department of Pathology, Faculty of Medicine, Cairo University, Egypt. Y1 - 2019 PY - 2019 VL - 20 IS - 8 SP - 2551 EP - 2561 KW - diethylnitrosamine KW - Ginger extract KW - oxidative stress KW - Inflammation KW - Proliferation DO - 10.31557/APJCP.2019.20.8.2551 N2 - Background: Diethylnitrosamine (DENA), a well-known dietary carcinogen, related to cancer initiation of variousorgans. The present study investigated the deleterious mechanisms involved in the early destructive changes of DENAin 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, anothergroup 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. Serumaspartate 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 factorerythroid2-related factor2 (Nrf2) in liver, stomach and colon. Histopathological studies and immunohistochemicalexamination of cyclooxygenase-2 (COX2) were conducted. Results: DENA induced elevation in liver function enzymeswith 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 inflammatoryfoci. Inflammatory foci displayed increased expression of COX2 in immunohistochemical staining. GE-pretreatmentimproved liver function and restored normal GSH with significant mitigation of oxidative stress and inflammatorybiomarkers 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 dependentmanner. Conclusion: GE exerted a potential anti-proliferative activity against DENA in liver, stomach and colon viaNrf2 activation, whilst suppression of oxidation and inflammation. UR - https://journal.waocp.org/article_88710.html L1 - https://journal.waocp.org/article_88710_d50a22011f0c8134d593f6965d1bb3ca.pdf ER -