• Title, Summary, Keyword: azoxymethane

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Luteolin, a Bioflavonoid, Attenuates Azoxymethane-Induced Effects on Mitochondrial Enzymes in Balb/c Mice

  • Pandurangan, Ashok Kumar;Sadagopan, Suresh Kumar Ananda;Dharmalingam, Prakash;Ganapasam, Sudhandiran
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6669-6672
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    • 2013
  • Colon cancer (CRC) is a serious health problem throughout the world. Development of novel drugs without side effects for this cancer is crucial. Luteolin (LUT), a bioflavonoid, has many beneficial effects such as antioxidant, anti-inflammatory and anti-proliferative potential. was a potent chemical carcinogen used for the induction of colon cancer. Colon carcinogenesis was initiated by intraperitoneal injection of azoxymethane (AOM) to mice at the dose of 15 mg/body kg weight in Balb/C mice for 3 weeks. Mice were treated with LUT at the dose of 1.2 mg/body kg weight orally. Mitochondrial enzymes such as isocitrate dehydrogenase (ICDH), ${\alpha}$-keto dehydrogenase (${\alpha}$-KDH), succinate dehydrogenase (SDH) and the activities of respiratory chain enzymes NADH dehydrogenase and cytochrome c oxidase were found to be elevated in AOM-treated animals. Treatment with LUT decreased the activities of all the parameters significantly. Hence, LUT might be a potent anticancer agent against colorectal cancer.

Effects of Lactic Acid Bacteria on intestinal Microbial Enzyme Activity and Composition in Rats Treated with Azoxymethane

  • Sang-Myeong;Lee, Wan-Kyu
    • Journal of Microbiology
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    • v.39 no.3
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    • pp.154-161
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    • 2001
  • In recent years, colon cancer has been reported to be one of the most important causes of cancer morbidity and mortality in Korea. Epidemiological and experimental studies suggest that lactic acid bacteria (LAB) used to ferment dairy products inhibits colon carcinogenesis. The present study was designed to determine whether the colon cancer inhibitory effect of LAB (Bifidobacterium longum Hy8001; Bif and Lactobacillus acidophilus HY2l04; Lac) of Korean origin, is associated with intestinal microflora composition and certain enzyme activity in rats treated with azoxymethane (AOM). At five weeks of age, SD rats were divided at random into four (AOM alone, Bif, Lac, and Bif+Lac) groups. Oral administration of lactic acid bacteria cultures were performed daily until the termination of the study. Two weeks later all animals were given a subcutaneous injection of AOM dissolved in normal saline at a dose of 15 mg/kg of body weight once weekly for 2 weeks. Every two weeks for 10 weeks, five of the rats in each group were randomly chosen for fecal specimen collection. The fecal specimens were used for assay of $\beta$-glucuronidase and nitroreductase, and analysis of intestinal microflora composition. The activity of $\beta$-glucuronidase which plays an important role in the production of the carcinogenic metabolite of azoxymethane was remarkably increased in the AOM alone group after AOM injection and maintained the high level during the experiment. However, LAB inhibited the AOM-induced increase in $\beta$-glucuronidase activity. Nitroreductase activity decreased by 30-40% in LAB treated groups in comparison with that of the AOM alone group. The results of the present study suggest that LAB inhibits colon carcinogenesis by modulating the metabolic activity of intestinal micro-flora and improving the composition of intestinal microflora.

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American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice

  • Yu, Chunhao;Wen, Xiao-Dong;Zhang, Zhiyu;Zhang, Chun-Feng;Wu, Xiao-Hui;Martin, Adiba;Du, Wei;He, Tong-Chuan;Wang, Chong-Zhi;Yuan, Chun-Su
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.14-21
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    • 2015
  • Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.

Canola Oil Influence on Azoxymethane-induced Colon Carcinogenesis, Hypertriglyceridemia and Hyperglycemia in Kunming Mice

  • He, Xiao-Qiong;Cichello, Simon Angelo;Duan, Jia-Li;Zhou, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2477-2483
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    • 2014
  • Azoxymethane (AOM) is a potent genotoxic carcinogen which specifically induces colon cancer. Hyperlipidemia and diabetes have several influences on colon cancer development, with genetic and environmental exposure aspects. Here, we investigated plasma lipid and glucose concentrations in Kunming mice randomized into four groups; control (no AOM or oil exposure), AOM control, AOM + pork oil, and AOM + canola oil. Aberrant crypt foci (ACF), plasma cholesterol, plasma triglyceride, plasma glucose and organ weight were examined 32 weeks after AOM injection. Results revealed that AOM exposure significantly increased ACF number, plasma triglyceride and glucose level. Further, male mice displayed a much higher plasma triglyceride level than female mice in the AOM control group. Dietary fat significantly inhibited AOM-induced hypertriglyceridemia, and canola oil had stronger inhibitory effect than pork oil. AOM-induced hyperglycemia had no sex-difference and was not significantly modified by dietary fat. However, AOM itself not change plasma cholesterol level. AOM significantly increased liver and spleen weight in male mice, but decreased kidney weight in female mice. On the other hand, mice testis weight decreased when fed canola oil. AOM could induce colorectal carcinogenesis, hypertriglyceridemia and hyperglycemia in Kunming mice at the same time, with subsequent studies required to investigate their genome association.

Antioxidant and Anti-inflammatory Effects of Yam (Dioscorea batatas Decne.) on Azoxymethane-induced Colonic Aberrant Crypt Foci in F344 Rats

  • Son, In Suk;Lee, Jeong Soon;Lee, Ju Yeon;Kwon, Chong Suk
    • Preventive Nutrition and Food Science
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    • v.19 no.2
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    • pp.82-88
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    • 2014
  • Yam (Dioscorea batatas Decne.) has long been used as a health food and oriental folk medicine because of its nutritional fortification, tonic, anti-diarrheal, anti-inflammatory, antitussive, and expectorant effects. Reactive oxygen species (ROS), which are known to be implicated in a range of diseases, may be important progenitors of carcinogenesis. The aim of this study was to investigate the modulatory effect of yam on antioxidant status and inflammatory conditions during azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. We measured the formation of aberrant crypt foci (ACF), hemolysate antioxidant enzyme activities, colonic mucosal antioxidant enzyme gene expression, and colonic mucosal inflammatory mediator gene expression. The feeding of yam prior to carcinogenesis significantly inhibited AOM-induced colonic ACF formation. In yam-administered rats, erythrocyte levels of glutathione, glutathione peroxidase (GPx), and catalase were increased and colonic mucosal gene expression of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and GPx were up-regulated compared to the AOM group. Colonic mucosal gene expression of inflammatory mediators (i.e., nuclear factor kappaB, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, and interleukin-1beta) was suppressed by the yam-supplemented diet. These results suggest that yam could be very useful for the prevention of colon cancer, as they enhance the antioxidant defense system and modulate inflammatory mediators.

Preventive Effects of Resveratrol against Azoxymethane Induced Damage in Rat Liver

  • Gurocak, Simay;Karabulut, Ercan;Karadag, Nese;Ozgor, Dincer;Ozkeles, Neslihan;Karabulut, Aysun Bay
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2367-2370
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    • 2013
  • Background: In recent years, due to modern lifestyles and exposure to chemical carcinogens, cancer cases are steadily increasing. From this standpoint, azoxymethane (AOM), a chemical carcinogen which causes de novo liver damage, and resveratrol, which is an antioxidant found in foods and protects against oxidative stress damage, are of interest. We here aimed to evaluate whether resveratrol could protect the liver tissues from the effects of AOM. Materials and Methods: The study was conducted in 4 groups, each consisting of seven rats, the first receiving only AOM (2 times per week, 5 mg/kg), group 2 AOM and resveratrol (2 times a week, 20 mg/kg), group 3 assessed only as a control and group 4 administered only resveratrol. At the end of the seventh week, the rats were sacrificed. Rat liver MDA, NO, GSH levels were analyzed biochemically, as well as the tissues being evaluated histopathologically. Results: MDA and NO increased in AOM group as signs of increased oxidative stress. The group concomitantly administered resveratrol was been found to be significantly decreased in MDA and NO levels and increased in GSH activity. However, there were no significant findings on histopathological evaluation. Conclusions: In the light of these results, resveratrol appears to exert protective effect on oxidative s tress in the liver tissue due to deleterious effects of chemical carcinogens.

Effect of Luteolin on the Levels of Glycoproteins During Azoxymethane-induced Colon Carcinogenesis in Mice

  • Pandurangan, Ashok Kumar;Dharmalingam, Prakash;Sadagopan, Suresh Kumar Ananda;Ganapasam, Sudhandiran
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1569-1573
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    • 2012
  • Luteolin (LUT), a bioflavonoid has been used as a chemopreventive agent world-wide against chemically induced cancer. Hence we designed an experiment to assess chemopreventive action of LUT on lipid peroxidation (LPO) and glycoconjugates in azoxymethane (AOM)-induced colon carcinogenesis. Colon cancer was induced by 15 mg/body kg. body weight of AOM and administration of LUT (at the dose of 1.2 mg/kg. body weight) was till end of the study. Analysis of lipid peroxidative end products such as protein carbonyl (PC), malonadehyde (MDA) and conjucated dienes (CD) demonstrated significant increase in in AOM-induced animals with reduction by LUT (p<0.05). Increased levels of glycoconjugates such as hexose, hexosamine, sialic acid, fucose and mucoprotein were analyzed in serum and colon tissues examined histopathologically by periodic acid Schiff's (PAS) staining were also reversed by LUT l(p<0.05). The secondary marker of colon cancer mucin depleted foci (MDF) was assessed in control and experimental group of animals. A characteristic increase of MDF was observed in AOM-induced colon cancer animals. Treatment with LUT decreased the incidence of MDF. These results suggest that LUT alters the expression of glycoconjugates and suppress colon cancer. Hence, we speculate that LUT can be used as a chemopreventive agent to treat colon cancer.

Nabag (Zizyphus spina-christi) Extract Prevents Aberrant Crypt Foci Development in Colons of Azoxymethane-Treated Rats by Abrogating Oxidative Stress and inducing Apoptosis

  • Guizani, Nejib;Waly, Mostafa Ibrahim;Singh, Vandita;Rahman, Mohammad Shafiur
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5031-5035
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    • 2013
  • Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.

Chemopreventive Effect of Chitosan on Rat Colon Carcinogenesis Induced by Azoxymethane (실험적 대장암 모델에서 키토산의 발암 억제효과에 관한 연구)

  • Han, Beom-Seok;Kim, Dae-Joong;Ahn, Byeong-Woo;Kim, Ki-Sok;Kang, Jin-Seok;Moon, Ji-Young;Hong, Choong-Man;Jang, Dong-Deuk
    • Korean Journal of Veterinary Pathology
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    • v.5 no.1
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    • pp.29-34
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    • 2001
  • This study was conducted to assess the chemopreventive effects of chitosan in a rat colon carcinogenesis induced by azoxymethane (AOM). Ninety, 5-week-old, male F344 rats were divided into three groups. The animals in group 1 received subcutaneous injections of 15mg/kg AOM three times for two weeks, then were placed on powdered basal diet containing 2% chitosan for 37 weeks from weeks 3 to 40. The animals in group 2 were given AOM alone. The animals in group 3 were given 2% chitosan without prior carcinogen treatment. All animals were sacrificed at week 12 for quantitative analysis of aberrant crypt foci (ACF) and at week 40 fur analysis of tumor induction. Total numbers of ACF and AC per colon of group 1 were not significantly different from those of group 2. Tumor incidences and multiplicities of small intestine in the group 1 were significantly decreased compared with those of the group 2 (P<0.05). According to pathological diagnoses, adenocarcinoma incidence and multiplicity in the small and large intestine in the group 1 were significantly decreased compared with those of the group 2 (p<0.05). No toxic effects were observed in animals given chitosan in terms of body weights, and liver or kidney histology. These results indicate that chitosan may have a potential as chemopreventive agents of colon carcinogenesis during the postinitiation stage.

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Modifying Effect of Indole-3-carbinol on Azoxymethane-induced Colon Carcinogenesis

  • Kang, Jin-Seok
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.381-385
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    • 2010
  • Indole-3-carbinol (I3C), one of naturally occurring main components in cauliflower vegetables, is supposed to have a chemopreventive potential in experimental animals and humans. This study was investigated to examine chemopreventive effect of I3C on colon carcinogenesis induced by azoxymethane (AOM) using C57BL/6J mice. Mice were divided into three groups (10 or 9 mice/group). All mice were subcutaneously injected with AOM (5 mg/kg body weight, four times at weekly interval). After AOM treatment, animals of group 1 were fed by AIN-76A pellets as a basal diet. Animals of groups 2 and 3 were given I3C containing diets (100 and 300 ppm in diets, respectively) for 6 weeks until sacrifice. All mice were sacrificed at week 10 and the aberrant crypt foci (ACF) of the colonic mucosa were assessed after staining with methylene blue. Total numbers of ACF/colon in group 2 ($10.1{\pm}5.1$) or group 3 ($10.6{\pm}5.3$) were decreased compared to the values of group 1 ($14.4{\pm}10.2$). Among numbers of ACF formation, 5, 7, 8 and 10 ACF in group 2 and 3 were greatly different those of group 1. Total numbers of aberrant crypts (AC)/colon of group 2 ($20.1{\pm}10.1$) or group 3 ($22.0{\pm}10.9$) were decreased compared to the value of group 1 ($33.7{\pm}24.7$). Taken together, it suggests that I3C treatment may retard mouse colon carcinogenesis even after administration of AOM.