title: Molecular mechanisms of nano-selenium in mitigating hepatocellular carcinoma induced by N-nitrosodiethylamine (NDEA) in rats.
abstract: The possible molecular mechanisms of Nano-selenium (nano-se) in attenuating hepatocellular carcinoma (HCC) was investigated in this study. To achieve this target, the apoptotic/necrotic rate in hepatic cells was investigated morphologically by double staining with acridine orange/ethidium bromide to address the type of cell death induced by nano-Se in HCC-bearing rats. To predict the oxidative stress and DNA damage, the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 2-deoxyguanosine (2-dG) was examined. Moreover, the expression of some HCC-related genes was investigated such as aldo-keto reductase 1B10 (Akr1b10), ING3 and Foxp1 genes. As well as the histopathological study of liver tissue sections was performed. The results obtained from this study revealed that (HCC+Nano Se) group shows the highest number of damaged cancerous cells. Furthermore, the necrotic/apoptotic rate was significantly higher in (nano-Se+HCC), (HCC+Doxo) and (HCC+Doxo+nano-se) compared to that in the untreated HCC group. Treatment of HCC group with nano-se decreased the ratio of 8-OHdG/2-dG generation significantly with respect to the untreated HCC group. The opposite was observed regarding the gene expression of AKr1b10 and ING3. The treatment of HCC group with nano-se elicited significant increase in the expression of Akr1b10 and ING3 genes compared with untreated HCC group. On the other hand, the expression of Foxp1 gene was significantly decreased in HCC group treated with nano-se in comparison with the untreated HCC group. The histopathological study provided a supportive evidence for the molecular genetics study. Our data shed light on the molecular mechanisms of nano-se in attenuating HCC in the experimental model.
authors.affiliation: Hormones Department, National Research Center , Dokki , Egypt .
authors.forename: Hanaa H
authors.initials: HH
authors.lastname: Ahmed
authors.forename: Wagdy K B
authors.initials: WK
authors.lastname: Khalil
authors.forename: Amal H
authors.initials: AH
authors.lastname: Hamza
mesh_terms: D000449:Aldehyde Reductase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000477:Alkylating Agents / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004249:DNA Damage / Q000187:drug effects; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012643:Selenium / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D016588:Anticarcinogenic Agents; D015415:Biomarkers; D002273:Carcinogens; D051858:Forkhead Transcription Factors; C561586:FoxP1 protein, rat; C000595580:ING3 protein, rat; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D004052:Diethylnitrosamine; C553248:Akr1b10 protein, rat; D000449:Aldehyde Reductase; D012643:Selenium
keywords: Apoptosis; HCC; HCC-related genes; nano-se; oxidative stress