Efecto del aceite de Sacha Inchi (Plukenetia volubilis L.) en la carcinogénesis de colon inducida por 1,2–dimetilhidrazina en ratas Holtzman / Effect of Sacha Inchi oil (Plukenetia volubilis L.) on 1,2–dimethylhydrazine-induced colon carcinogenesis in Holtzman rats

Objetivos: Evaluar el efecto protector del aceite de Sacha Inchi (ASI) sobre el desarrollo de cáncer de colon (CC) inducido con 1,2–dimetilhidrazina (DMH) en ratas Holtzman. Materiales y métodos: Estudio experimental con 28 ratas albinas machos de la cepa Holtzman distribuidas al azar en 4 grupos: un grupo control positivo expuesto a DMH (C1), un grupo control negativo expuesto a ASI a 150 μL/kg/día (C2), y dos grupos experimentales expuestos a DMH con ASI a 150 μL/kg/día (E1) y ASI a 300 μL/kg/día (E2). La DMH se aplicó por 8 semanas y con un tiempo total de inducción de 22 semanas. Luego se realizó el análisis patológico mediante la identificación de lesiones tumorales cancerosas en los intestinos. El efecto protector se evaluó en base a las proporciones de ausencia de lesión en los grupos expuestos a DMH. Resultados: Se identificaron lesiones tumorales cancerosas en: dos especímenes del grupo C1, un espécimen del grupo E1 y dos especímenes del grupo E2. No se identificaron lesiones intestinales en el grupo C2. Las proporciones de ausencia de lesión fueron: en el grupo C1 de 75%, en el grupo E1 de 87,5% y en el grupo E2 de 75%. No se encontraron diferencias significativas (p>0,05). Conclusiones: No se evidenció un efecto protector significativo del ASI sobre el desarrollo de CC inducido con DMH en ratas Holtzman, respecto al grupo control.

Objectives: To evaluate the preventive effect of Sacha Inchi oil (SIO) on 1,2–dimethylhydrazine (DMH)-induced colon carcinogenesis (CC) in Holtzman rats. Materials and methods: Experimental study with 28 Holtzman male albino rats randomly distributed into 4 groups: a positive control group exposed to DMH (C1), a negative control group exposed to SIO at 150 uL/kg/ day (C2), and two experimental groups exposed to DMH with SIO at 150 uL/kg/day (E1) and SIO at 300 uL/kg/day (E2). The DMH was applied for 8 weeks and the total induction time was 22 weeks. Pathological examination was performed by identifying cancerous tumor lesions in the guts. The preventive effect was evaluated based on proportions of lack of lesion in the groups exposed to DMH. Results: Cancerous tumor lesions were identified in: two specimens of group C1, one specimen of group E1 and two specimens of group E2. No intestinal lesions were identified in group C2. The proportions of lack of lesion were: in group C1 of 75%, in group E1 of 87.5% and group E2 of 75%. No significant differences were found (p>0.05). Conclusions: It was not found a significant protective effect of SIO on DMH-induced CC in Holtzman rats, compared to control group.

Efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido con 1,2-dimetilhidrazina en ratas / Chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine

RESUMEN Objetivos Determinar la toxicidad y el efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido en ratas con 1,2 dimetilhidrazina (DMH). Materiales y métodos Se obtuvo el extracto alcaloideo de la parte carnosa de Melocactus bellavistensis, posteriormente, se realizó un ensayo de toxicidad aguda en 30 ratones de cepas Balb C57. Para evaluar su efecto quimioprotector se indujo el cáncer de colon en 45 ratas Holtzmann con DMH, según el siguiente diseño experimental: un grupo control con: polisorbato de sodio (PS) a 2 mL/kg y cuatro grupos con DMH 20 mg/kg más 0, 1, 5 y 10 mg/kg de extracto alcaloideo de Melocactus bellavistensis respectivamente. Resultados Con una muestra de 5 g de extracto alcaloideo se determinó una DL50 mayor a 1000 mg/mL en el ensayo de toxicidad aguda del extracto alcaloideo de Melocactus bellavistensis. Los resultados del efecto quimioprotector en los indicadores de estudio histopatológico revelaron que a las dosis de 5 y 10 mg/kg demostraron actividad antitumoral significativa en el cáncer de colon inducido por dimetilhidrazina en ratas con 100% de inhibición de neoplasia. Conclusiones En condiciones experimentales, el extracto de alcaloides de Melocactus bellavistensis demostró tener efecto quimioprotector en cáncer de colon inducido por dimetilhidrazina en ratas.

ABSTRACT Objectives To determine the toxicity and chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine (DMH). Materials and methods The alkaloid extract was obtained from the fleshy part of M. bellavistensis, and an acute toxicity test was then carried out on 30 mice of the Balb C57 strain. To assess its chemoprotective effect, colon cancer was induced in 45 Holtzman rats using DMH according to the following experimental design: one control group received 2 mL/kg sodium polysorbate, and four groups received 20 mg/kg DMH plus 0, 1, 5, or 10 mg/kg M. bellavistensis alkaloid extract. Results With a sample of 5 g of alkaloid extract, an LD50 greater than 1000 mg/mL was determined in the acute toxicity test. Histological indicators revealed that the 5 and 10 mg/kg doses had significant anti-tumor activity with 100% neoplasia inhibition against DMH- induced colon cancer in rats. Conclusions Under experimental conditions, the alkaloid extract of M. bellavistensis has a chemoprotective effect against DMH-induced colon cancer in rats.

Comparative study of 1, 2-dimethylhydrazine and azoxymethane on the induction of colorectal cancer in rats / Estudo comparativo das substâncias 1, 2-dimetil-hidrazina e azoximetano na indução de câncer colorretal em ratos

The induced colorectal carcinogenesis in rodents has a long history and currently uses the substances 1,2-dimethylhydrazine and azoxymethane. Objective: The aim of this study was to compare the inductive effect of the substances azoxymethane and 1,2-dimethylhydrazine in colorectal carcinogenesis. Method: 30 randomly chosen male Wistar rats were divided into four groups. G1 group was treated with 1,2-dimethylhydrazine and C1 was its control group; G2 group was treated azoxymethane and C2 was its control group. The animals were weekly weighed until euthanasia, when their intestines were removed, processed and analyzed by an experienced pathologist. Results: Among the control groups (C1 and C2) no histologic changes were observed; moderate dysplasia was detected in G2 group; hyperplasia, mild dysplasia, severe dysplasia and carcinoma were observed in G1 group. When this study compared the cost of the substances, 1,2-dimethylhydrazine was more than 50 times less expensive than azoxymethane. Conclusion: Azoxymethane is able to promote histological changes consistent with colorectal carcinogenesis. 1,2-Dimethylhydrazine produced neoplasia and dysplasia, and, compared to the azoxymethane, was more efficient in the induction of colorectal cancer. (AU)

A carcinogênese colorretal induzida em roedores tem longa história e utiliza, atualmente, as substâncias 1,2 dimetil-hidrazina (DMH) e azoximetano (AOM). Objetivo: Comparar o efeito indutivo das substâncias AOM e DMH para o câncer colorretal (CCR). Método: 30 ratos Wistar machos foram randomizados em quatro grupos. O grupo G1 foi inoculado com DMH, o grupo C1 foi seu controle; G2 recebeu o AOM e C2 foi seu controle. Os animais foram pesados semanalmente até a eutanásia, quando tiveram seus intestinos retirados, processados e analisados por um patologista experiente. Resultados: Os animais dos grupos de controle apresentaram tecido colorretal normal e os animais do grupo G2 apresentaram um padrão de displasia moderada. Nas lâminas do grupo G1, foram encontradas regiões de hiperplasia, displasia leve, displasia grave, e carcinoma. Comparado o custo das substâncias AOM e DMH, este último teve um preço mais de 50 vezes menor ao do AOM. Conclusão: AOM é capaz de promover alterações histológicas compatíveis com a carcinogênese colorretal. DMH produziu neoplasia e displasia grave e, comparada ao AOM, foi mais eficiente na indução do câncer colorretal. (AU)

Experimental study of mustard seeds prevent colorectal tumor by antioxidation and immune deviation / 中国癌症杂志

Background and purpose:Recently, a large number of researches have shown that cruciferous plants have the chemopreventive effect on tumor. Mechanisms of antitumorigenesis were investigated on antioxidation, antimutation, immunity and inducing apoptosis, and so on. Mustard seeds (MS) are the seeds belong to the cruciferous plants. This study aimed to investigate antioxidation and immune deviation of MS on colorectal tumor in rats induced by 1, 2-dimethylhydrazine (DMH). Methods:A total of 48 male Wistar rats were randomly divided into four groups:DMH alone, DMH+5%MS, DMH+7.5%MS, and the untreated control group(Saline). Colorectal tumorigenesis was induced by intraperitoneal injecting 30 mg/kg DMH once a week for 20 weeks. At the end of 32 weeks, the rats were sacrificed, then colorectal tumor incidence was observed and histological type was determined by HE staining. A colorimetric assay was used to detect levels of the lipid peroxidation product malondialdehyde (MDA) and the activity of antioxidant enzymes in the serum of all rats. The levels of Th1 and Th2 cytokines were detected with Luminex200. Results: No tumorous lesion was found in the untreated control group. However, the total tumor incidence in DMH+5%MS group and DMH+7.5%MS group was signiifcantly decreased 33.3%and 58.3%respectively, compared with the DMH group’s (100%, P<0.05). As DMH induced colorectal tumorigenesis, MDA and Th2 cytokines in the serum were signiifcantly higher in the DMH group than those in the untreated control group (P<0.05), but the activities of antioxidant enzymes were signiifcantly lower (P<0.05). While the MS treatment, compared with the DMH group, signiifcantly suppressed the MDA level but enhanced the activities of antioxidant enzymes and levels of Th1 cytokines (P<0.05). Conclusion: MS significantly decrease prevalence rates of DMH-induced colorectal tumor in rats. The mechanism may be related with the antioxidation and immune balance deviation.

Effect of high-fat diet on 1,2-dimethylhydrazine-induced colon tumors / 中华临床营养杂志

Objective To explore the effect of fat on 1,2-dimethylhydrazine (DMH)-induced colon tumors.Methods A total of 50 7-week-old male Wistar rats were further divided into four groups:standard diet feed control group (n =10),standard diet feed plus DMH-induced tumor group (SDT,n =15),high-fat diet feed control group (n =10) and high-fat diet feed plus DMH-induced tumor group (HFDT,n =15).Rats were killed 18 weeks later,and enzyme-linked immunosorbent assay was used to detect serum triglyeeride,tumor necrosis factor (TNF-α),and colonic TNF-α,interleukin-6.After the intestinal tracts were removed,the location,amount,and size of the tumors were observed.The pathological changes of the tissue sections were observed,and the distributions of TNF-α and Ki-67 in the normal tissues and tumors were detected by immunohistochemistry.Results Upon the completion of the study,the mortality rate of rats was 20.00％ in the SDT group and 26.67％ in the HFDT group,the tumor formation rate was 75.00％ in the SDT group and 81.82％ in the HFDT group,and the tumor-bearing rate was 117％ in the SDT group and 191％ in the HFDT group.No statistical significance difference between the two groups in mortality rate,tumor formation rate (P =0.545) and tumor bearing rate (x2 =1.343,P =0.247).The average tumor volume was significantly different between the standard diet feed control group and high-fat diet feed control group (28.57％ vs 66.67％,P =0.030).Also,the serum triglyceride and TNF-α levels significantly differed between the SDT group and HFDT group [TG (1.39 ± 0.31) mmol/L and TNF-α (124.80 ± 21.69) ng/L in the HFDT group and TG (0.46 ±0.20) mmol/L and TNF-α (85.83 ± 17.45) ng/L in the SDT group] (P =0.000).The expressions of TNF-α,IL-6,and Ki-67 in colonic mucosa were significantly higher in the high-fat diet feed control group than in the standard diet feed control group [TNF-α:(6.22 ± 0.63) ng/g vs (2.33 ± 0.44) ng/g,P=0.020; IL-6:(13.50±0.67) ng/gvs (7.31 ±0.41) ng/g,P=0.000; and Ki-67:40％ vs 10％,P =0.028].The Ki-67 expression rate was 90.48％ in the HFDT group,compared to 50％ in the SDT group (P =0.015).Conclusions High-fat diet can increase the serum triglyceride and TNF-α levels in rats,upregulate the expressions of TNF-α,IL-6 and Ki-67,and thus promote inflammation and cell proliferation,and ultimately affect the tumor formation and development.However,the effect of fat on DMH-induced colon tumors warrants further studies.

Colon cancer and swimming exercise: effect on wistar rat testes

This study was undertaken to determine whether colon cancer (CC) and chronic swimming exercise alter rat testis. Eleven weeks old rats were distributed into control group (n=6) and the groups that were induced to develop CC by dimethylhydrazine injections (nEG, EG0, EG2 and EG4; n=10 each group). In the group nEG, the rats did not swim, whereas groups EG0, EG2 and EG4, underwent a swimming program with distinct loads (0, 2 and 4% of body mass, respectively) for 35 weeks. The morphometry, stereology and cell counts showed damage caused by the CC on the germ epithelium. These results were noteworthy since this was the first report to associate the CC with testicular damage. Swimming exercise had no significant role in reducing, or increasing the CC effects on the testis, despite having slightly improved the testis structure of the exercised rats without load. In conclusion, CC caused testis impairment, which could not be avoided by the swimming exercise.

Effect of probiotics on the development of dimethylhydrazine-induced preneoplastic lesions in the mice colon

PURPOSE: To determine the effect of probiotics on the development of chemically induced (1, 2-dimethylhydrazine) colonic preneoplastic lesions, in mice. METHODS: The animals were divided into five groups. The control group was injected with carcinogen alone and the other groups also received probiotics (1- Lactobacillus delbrueckii UFV-H2b20; 2- Bifidobacterium animalis var. lactis Bb12; 3- L. delbrueckii UFV-H2b20 plus B. animalis var. lactis Bb12; and 4- Saccharomyces boulardii) administered orally in drinking water throughout fourteen weeks. RESULTS: Consumption of lactobacilli and bifidobacteria alone resulted in a significant reduction of the total number of aberrant crypt foci (55.7% and 45.1%, respectively). Significant reduction in the number of these small foci (<3 aberrant crypts) was only observed in the group treated with lactobacilli (52.2%) in comparison to control group. The number of larger foci (>3 aberrant crypts) crypts had no significant reduction. CONCLUSION: L. delbrueckii UFV-H2b20 and B. animalis var. lactis Bb12 administered alone protect colonic preneoplastic lesions in mice, while the combined treatment of these bacteria and the administration of S.boulardii were not effective in reducing such colonic lesions.

Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1, 2-dimethylhydrazine-induced colon cancer

We determined the effect of long-term aerobic swimming training regimens of different intensities on colonic carcinogenesis in rats. Male Wistar rats (11 weeks old) were given 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethyl-hydrazine (DMH, dissolved in 0.9 percent NaCl containing 1.5 percent EDTA, pH 6.5), at 3-day intervals and divided into three exercise groups that swam with 0 percent body weight (EG1, N = 11), 2 percent body weight (EG2, N = 11), and 4 percent body weight of load (EG3, N = 10), 20 min/day, 5 days/week for 35 weeks, and one sedentary control group (CG, N = 10). At sacrifice, the colon was removed and counted for tumors and aberrant crypt foci. Tumor size was measured and intra-abdominal fat was weighed. The mean number of aberrant crypt foci was reduced only for EG2 compared to CG (26.21 ± 2.99 vs 36.40 ± 1.53 crypts; P < 0.05). Tumor incidence was not significantly different among groups (CG: 90 percent; EG1: 72.7 percent; EG2: 90 percent; EG3: 80 percent). Swimming training did not affect either tumor multiplicity (CG: 2.30 ± 0.58; EG1: 2.09 ± 0.44; EG2: 1.27 ± 0.19; EG3: 1.50 ± 0.48 tumors) or size (CG: 1.78 ± 0.24; EG1: 1.81 ± 0.14; EG2: 1.55 ± 0.21; EG3: 2.17 ± 0.22 cm³). Intra-abdominal fat was not significantly different among groups (CG: 10.54 ± 2.73; EG1: 6.12 ± 1.15; EG2: 7.85 ± 1.24; EG3: 5.11 ± 0.74 g). Aerobic swimming training with 2 percent body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat.

The Antitumor Effects in vitro and Impact on Colon Cancer in Rats of Endostatin Transfected Bifidobacterium Oral Powder Preparation / 医学研究杂志

Objective To study the antitumor effects in vitro and impact on colon cancer in rats of endostatin transfected bifidobacterium oral powder preparation(ETB-2).Methods Growth inhibitory effect of the cecropins on normal human gastric epithelial cell line(GES-1) and human colon adenocarcinoma cell line(LS-174T) was observed using a microculturetetrazolium(MTT) colorimetric methods.Male Wistar rats were divided into 4 groups.All treatments were completed in a course of 18 weeks and the experiment was finished at week 33.Results The cecropins showed selective cytotoxic activity against the human colon adenocarcinoma cell line.There was a significant lower in incidence of colon tumors in rats(70%vs100%,P0.05).Conclusion ETB-2 has significant preventive effect on colon cancer induced by DMH in rats.

Inhibition by Ginseng of Colon Carcinogenesis in Rats

The inhibitory effects of ginseng on the development of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in the colon were investigated in rats. Male, 6-week-old rats were injected with DMH once a week for 4 weeks. Rats in Groups 1 and 2 were fed diets containing red and white ginseng, rerspectively, at a dose of 1% for 5 weeks, starting one week before the first treatment of DMH. Animals in Groups 3 and 4 received red or white ginseng for 8 weeks starting after DMH treatment. Group 5 served as a carcinogen control group. Numbers of ACF with at least four crypts were significantly reduced in the colon of Group 2 treated with red ginseng combined with DMH. Moreover, rats were injected with DMH 4 times at one-week intervals. They were also fed diets containing 1% red or white ginseng or the control diet throughout 30 days of the experiment. Treatment with red ginseng resulted in a significant decrease of 5- bromo-2'-deoxyuridine labeling indices in colonic crypts comprising ACF. These findings suggest that dietary administration of red ginseng in combination with DMH suppresses colon carcinogenesis in rats, and the inhibition may be associated, in part, with inhibition of cell proliferation, acting on ACF in the colonic mucosa.