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Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

World Journal of Gastroenterology 2009年第11期15卷 1373-1380页

作者： Salim S Al-Rejaie Abdulaziz M Aleisa Abdulaziz A Al-Yahya Saleh A Bakheet Abdulmalik Alsheikh Amal G Fatani Othman A Al-Shabanah Mohamed M Sayed-Ahmed Department of Pharmacology College of PharmacyKing Saud UniversityPO Box 2457Kingdom of Saudi Arabia Department of Pathology College of MedicineKing Saud UniversityPO Box 2457 Kingdom of Saudi Arabia

AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each *** in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 *** in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 *** in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn *** in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group *** in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group ***:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver *** the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver ***, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control *** examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-

关键词： Carnitine deficiency D-carnitine L-carnitine diethylnitrosamine Hepatic carcinogenesis

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Rhizoma paridis saponins protected against liver injury in diethylnitrosamine-induced mice

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Traditional Medicine Research 2023年第2期8卷 7-12页

作者： Chen Luo Jing-Wen Yao Shu-Li Man Wen-Yuan Gao Key Laboratory of Industrial Microbiology Ministry of Education/Tianjin Key Laboratory of Industry Microbiology/National and Local United Engineering Lab of Metabolic Control Fermentation Technology/College of BiotechnologyTianjin University of Science&TechnologyTianjin 300457China Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China

Background:diethylnitrosamine,one of food additives,possessed a strong carcinogenic effect in *** paridis saponins,as the main active components of Paris polyphylla,have a good anti-cancer effect in our previous *** verify their inhibitory effect on diethylnitrosamine-induced liver cancer,we carried out this ***:We established diethylnitrosamine-induced mouse hepatocarcinoma models to evaluate antitumor of Rhizoma paridis ***,gas chromatography-mass spectrometry was applied to analyze the metabolites in the urine and serum ***:Rhizoma paridis saponins alleviated diethylnitrosamine-induced *** the one hand,Rhizoma paridis saponins down-regulated the levels of liver function markers,such as alanine aminotransferase,aspartate transaminase and alpha *** the other hand,Rhizoma paridis saponins reduced metabolic disorders by increasing fructose and mannose metabolism,and decreasing pentose and glucuronate interconversion,inositol phosphate metabolism,and the process of saturated fatty acids transforming to unsaturated fatty acids,which based on the regulating mRNA expression of glucose transporter type 4,lactate dehydrogenase A,fatty acid synthetas,acetyl-CoA carboxylase and apolipoprotein ***:Rhizoma paridis saponins has the potential application to inhibit chemical-induced hepatocarcinogenesis in the future.

关键词： Rhizoma paridis saponins liver injury diethylnitrosamine metabolites

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Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

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World Journal of Hepatology 2021年第3期13卷 328-342页

作者： Amany Helmy Hasanin Eman K Habib Nesreen El Gayar Marwa Matboli Clinical Pharmacology Department Faculty of MedicineAin Shams UniversityCairo 11318Egypt Anatomy and Embryology Department Faculty of MedicineAin Shams UniversityCairo 11318Egypt Medical Biochemistry and Molecular Biology Department Faculty of MedicineAin Shams UniversityCairo 11381Egypt

BACKGROUND diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged *** To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of *** The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF *** were sacrificed after 10 wk and 16 *** functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were *** mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the *** 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and *** 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent *** actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

关键词： Acetylaminofluorene Hepatic precancerous lesion diethylnitrosamine Autophagy Apoptosis MicroRNA

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Short and Long Term Effects of Pomegranate （Punica Granatum） Extracts on Apoptosis in Rat Kidney Induced by diethylnitrosamine and Phenobarbital

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Journal of Pharmacy and Pharmacology 2016年第2期4卷 52-63页

作者： Asmaa F. Hamouda Nadia Z. Shaban Biochemistry Departement Faculty of Science Alexandria University Alexandria 21111 Egypt

Pomegranate （Punica granatum L.） has strong anti-inflammatory, antioxidant, anti obesity, and anticancer effects. The effect of different pomegranate extracts, PE （peel extract）, SOE （seed oil extract）, and PJ （pomegranate juice） extract on levels of kidney caspase-3, DNAF （DNA fragmentation） and kidney function tests in rats treated and untreated with DEN （diethyl nitrosamine） and PB （Phenobarbital） during short （35 days） and long （154 days） period was studied. Injected of rats with DEN and PB caused an increased in the levels ofDNAF, caspase-3 and kidney function tests, compared to the control in both period of study. Treatment of rats with PE, SOE, PJ pre, during, and post DEN and PB administration improved kidney function and decreased the levels of DNAF, and caspase-3 activities compared to the DEN group in both period of study, indicates that PE, SOE, PJ reduced and treatment apoptosis induced by DEN and PB. Treatment of healthy rats with PE, SOE, and PJ only for 35 days not increased kidney function or induced apoptosis for kidney tissues. Treatment with PJ alone in healthy kidney induced apoptosis which was higher than that induced by SOE and PE in case of long period study, this mean that fresh fruit or pomegranate juice safe for healthy in general at harvesting season only.

关键词： Kidney apoptosis diethylnitrosamine phenobarbital DNA fragmentation pomegranate.

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Chronic Alcohol Consumption Promotes diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances

Chronic Alcohol Consumption Promotes Diethylnitrosamine-Indu...

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第十一届全国免疫学学术大会

作者： Yan Guoxiu University of Science and Technology of China

Background and aims:Chronic alcohol consumption increases the risk of hepatocellular carcinoma(HCC),a typical in ammation-associated ***,little is known about the potential immunological mechanisms by which ethanol affects tumor ***:Adult male mice were administered multiple doses of diethylnitrosamine(DEN).Four and a half months later,animals were placed on a liquid Lieber-De Carli diet containing 5% ethanol for 2.5 *** the end of the study,liver tissue samples were obtained to analyze liver pathology and gene expression,and hepatic mononuclear cells(MNCs) were isolated to analyze immune ***:The progression of hepatic tumors(characterized by the ratio of liver weight to body weight,and the tumor volume and diameter) after chronic ethanol consumption was enhanced in mice treated with ***,alcohol consumption was associated with alcoholic steatohepatitis,fibrosis,and epithelial-mesenchymal transition(EMT).Furthermore,chronic alcohol consumption decreased the number of antitumor CD8+ T cells and natural killer(NK) cells but increased the number of tumor-associated macrophages(TAMs) and natural killer T(NKT) ***,the level of Th1-type cytokines diminished,but the level of Th2-type and Th17-type cytokines ***:These data demonstrate that chronic alcohol consumption exacerbates DEN-induced hepatocarcinogenesis by aggravating hepatic pathological injury and impairing antitumor *** the immune system is a potential therapeutic regimen for alcohol-promoted HCC.

关键词： alcohol hepatocellular carcinoma diethylnitrosamine immune cells antitumor immunity

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Kupffer cell and apoptosis in experimental HCC

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World Journal of Gastroenterology 2000年第3期6卷 405-407页

作者： Zhu HZ Ruan YB Wu ZB Zhang CM Tongji Med Univ Dept Ultrastruct Pathol Wuhan 430030 Hubei Province Peoples R China

INTRODUCTION Our previous study has proved that Kupffer cellsmay have an inhibitory effect on the process ofhepatocarcinogenesis,however,their inhibitorymechanism needs exploring *** performed acomparative study on the expression of PCNA,Bax,P53 and apoptosis of liver cancer cells usingimmunohistochemical technology and terminaldeoxynucleotidyl transferase (TdT)-mediateddUTP-digoxigenin nick end labeling(TUNEL)

关键词： liver noplasms experimental diethylnitrosamine apoptosis protein P53 Kupffer’s cell

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Effects on the Tumor Specific Growth Factor and Tumor Necrosis Factorαin Rats'Precancerous Lesion of Primary Hepatocellular Carcinoma by Direct Moxibustion at Ganshu(BL 18)Acupoint

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Chinese Journal of Integrative Medicine 2016年第7期22卷 532-536页

作者：王培朱江谢锡亮睢明河张秋菊贾文睿辛思源柳杨侯中伟 School of Acupuncture-moxibustion and Tuina Beijing University of Chinese MedicineBeijing(100029)China The Key Unit of Evaluation of Characteristic Acupuncture Therapy State Administration of Traditional Chinese MedicineBeijing(100029)China The Research Institute of Acupuncture and Moxibustion in Houma City HoumaShanxi Province(043001)China School of Preclinical Medicine Beijing University of Chinese MedicineBeijing(100029)China Chengde Medical Colleoe.Chenade.Hebei Province(067000) China

Objective： To investigate the effect of direct moxibustion at Ganshu （BL18） on the serum concentrations of tumor specific growth factor （TSGF） and tumor necrosis factor a （TNF-a） in a rat model with precancerous lesion of primary hepatocellular carcinoma （HCC）, so as to explore the mechanism of moxibustion underlying improvement of HCC. Methods： Sixty male Wistar rats were randomly divided into control group （n=10）, model group （n=20）, prevention group 1 （n=15） and prevention group 2 （n=15）. The normal rats were injected with physiological saline as blank control. At the same time, the rats of other three groups were injected with diethylnitrosamine to establish the HCC model. Direct moxibusUon with grain-sized moxa was applied to bilateral Ganshu acupoint of the rats in the prevention group 1 （1 treatment course, 20 days） and prevention group 2 （2 treatment courses, 40 days）, 5 doses for each acupoint, 0.5 mg/dose, once every other day. At each time point （before model establishment, the end of 1st course prevention, the end of 2rid course prevention and the end of model establishment）, serum levels of TSGF and TNF-eL were detected using enzyme-linked immunosorbent assay. Results： Compared with the control group, there was a remarkably increase of serum TSGF and TNF-eL contents in the model group at the end of the experiment （P〈0.05）. At the end of the 1st course of direct moxibustion, the contents of serum TSGF and TNF- a of rats in the prevention group 1 were significantly increased compared with that of the model group （P〈0.05）. At the end of the 2nd course of direct moxibustion, serum TSGF and TNF-a levels of rats in the model group were higher than the normal group with significantly difference （P〈0.05）, and the levels of TSGF and TNF-a in the prevention group 2 were significantly reduced in comparison with the model group （P〈0.05）. Conclusion： It was possible that direct moxibustion could inhibit precancerous lesion and postpone hepatocarcinogenesis, and the

关键词： direct moxibustion diethylnitrosamine hepatocellular carcinoma tumor specific growth factor tumor necrosis factor a Chinese medicine

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INHIBITORY EFFECT OF BOSCHNIAKIA ROSSICA ON DEN-INDUCED PRECANCEROUS HEPATIC FOCI AND ITS ANTIOXIDATIVE ACTIVITIES IN RATS

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Chinese Journal of Cancer Research 1999年第3期11卷 169-173页

作者：尹宗柱金海玲沈明花李天洙全吉淑 Biochemistry Laboratory for Cancer Research Yanbian University College of Medicine Yanji Jilin Province China

Objective: To investigate the inhibitory effect of Boschniakia rossica (BR) on rat precancerous hepatic foci induced by diethylnitrosamine (DEN) and its antioxidative activities. Methods: The expression of tumor marker—placental form glutathione S-transferase (GST-P), p53 and p21 protein were investigated by immunohistochemistry techniques using ABC method. TNF-α was measured by ELISA and antioxidative activities of SOD, MDA, GSH-Px, GST and CAT were investigated by colorimetric method in rat serum and mitochondria of liver cells. Results: The 500 mg/kg of BR-H2O extract fraction from BR-methanol extract had inhibitory effect on the formation of DEN-induced GST-P-positive foci in rat liver and the expression of mutant p53 and p21 protein was lower than that of hepatic precancerous lesions. The serum TNF-α was increased by the administration of BR extract in the early stage of chemical hepatocarcinogenesis in rat livers. The serum and liver cells mitochondria activities of SOD and GSH-Px rose again in rats administered with BR-H2O extract and the increasing activity of GST and content of MDA in the hepatic precancerous were decreased by the BH-H2O extract. Conclusion: These results indicated that BR-H2O extract has inhibitory effect on DEN-induced precancerous hepatic foci in rats and induced TNF-α production in rats. The antioxidative action was exhibited by the administration of BR-H2O extract in the early stage of chemical hepatocarcinogenesis in rat livers.

关键词： Bioschniakia rossica Placental form glutathione S-transferase Hepatocarcinogenesis Antioxidation TNF-α diethylnitrosamine

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Preliminary Investigation on Regulating Effects of Different TCM Treatments on Transcription of the Correlated Genes of Liver Cancer in Rats

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Journal of Traditional Chinese Medicine 2003年第1期23卷 62-66页

作者：管冬元方肇勤等 BasicMedicineInstituteofShanghaiTCMUniversity Shanghai200032

The regulating effects of TCM treatments including clearing away heat and toxic materials,promoting blood circulation and removing blood stasis,and strengthening the spleen and regulating qi on the oncogene transcription were observed in the liver cancer model *** preliminary results indicated that the mRNA levels of H-ras N-ras and K-ras,and signal molecules correlated with the ras/MAPK signal transduction pathway were down-regulated by the different TCM treatments in varying ***,the regulating effects of the treatments on differently-displayed genes were *** is suggested that the molecular mechanisms of the TCM treatments for liver cancer was complex with different target genes.

关键词： Animals diethylnitrosamine Drugs, Chinese Herbal Genes, ras Liver Neoplasms, Experimental Male Mitogen-Activated Protein Kinase Kinases Protein-Serine-Threonine Kinases RNA, Messenger Rats Rats, Wistar Signal Transduction Transcription, Genetic ras Proteins

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A modified rat model for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2004年第4期3卷 585-587页

作者： Fu-Chun Yang, Shu-Sen Zheng and Tian-An Jiang Hangzhou, China Department of Hepatobiliary Pancreatic Surgery and Liver Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Department of Hepatobiliary Pancreatic Surgery and Liver Transplantation Center First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China.

BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

关键词： hepatocellular carcinoma model rat diethylnitrosamine

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