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Asian Pacific Journal of Cancer... Jun 2018Introduction: Colon Cancer remains one of the major worldwide causes of cancer related morbidity and mortality in both genders. Berberine (BBR), a major component of...
Introduction: Colon Cancer remains one of the major worldwide causes of cancer related morbidity and mortality in both genders. Berberine (BBR), a major component of alkaloids that possess a variety of pharmacological properties. Objective: This study shows the ameliorating roles of berberine on 1,2 Di methyl hydrazine (DMH) induced colon cancer in male Swiss albino rats. Methods: The rats were segregated into four groups: group 1, control rats; group 2, rats were orally received berberine (75 mg/kg b.wt./day) daily for ten weeks; group 3,rats were subcutaneously injected with DMH (20 mg/kg b.wt) once a week for 8 weeks ,group 4, rats were treated firstly with berberine for two weeks before DMH intoxication and concurrently with DMH over 8 weeks. Result: DMH injection decreased the antioxidants levels (GSH and SOD) and increased inflammatory markers (MPO, MAPK and COX-2). Moreover, it downregulated apoptotic markers (Caspase-3 and P53) expression that confirmed by colon cell proliferation. The prophylactic effect of berberine was noticed as its pre-and co-administration increased antioxidants status and apoptotic markers expression that associated with inflammatory markers down-regulation with absence of proliferated colon cells. Conclusion: Therefore, the overall findings proved that the anti-proliferative effect of berberine return to its antioxidants and anti-inflammatory properties that activated the programmed cell death process.
Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; Apoptosis; Berberine; Carcinogens; Cell Proliferation; Colonic Neoplasms; Inflammation Mediators; Male; Rats
PubMed: 29938466
DOI: 10.22034/APJCP.2018.19.6.1685 -
Journal of Nutritional Science and... 2010Coenzyme Q10 (CoQ10) is known to be a compound with mitochondrial bioenergetic functions and antioxidant activity. In this study, we evaluated the effect of CoQ10 on the...
Coenzyme Q10 (CoQ10) is known to be a compound with mitochondrial bioenergetic functions and antioxidant activity. In this study, we evaluated the effect of CoQ10 on the formation of aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH), DMH-induced leukocytic DNA damage and gene expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by real-time PCR in colonic mucosa of male SD rats. The animals were divided into three groups and fed a casein-based high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) with or without CoQ10 (0.4 mg in soybean oil/kg BW/d, i.p.). One week after beginning the diets, the rats were subjected to 6 wk of treatment with DMH (30 mg/kg/wk, s.c.) and CoQ10 treatments continued over the entirety of the experimental period (59 d). Administration of CoQ10 resulted in reduction of ACF numbers, to 20% of the carcinogen control value. CoQ10 supplementation induced an antigenotoxic effect on DMH-induced DNA damage in the blood cells. Colonic mucosa of DMH-injected rats had significantly greater COX-2 and iNOS gene expression than those of control rats, while treatment with CoQ10 induced an inhibitory effect on over-expression of COX-2 and iNOS in colon tumors. Our results provide evidence that CoQ10 has a protective effect on the process of colon carcinogenesis, suppressing the development of preneoplastic lesions, possibly by modulating COX-2 and iNOS gene expression in colonic mucosa and DNA damage in leukocytes, suggesting that CoQ10 has chemotherapeutic activity.
Topics: 1,2-Dimethylhydrazine; Analysis of Variance; Animals; Anticarcinogenic Agents; Antioxidants; Colon; Colonic Neoplasms; Cyclooxygenase 2; DNA Damage; Intestinal Mucosa; Male; Nitric Oxide Synthase Type II; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Ubiquinone
PubMed: 20495296
DOI: 10.3177/jnsv.56.139 -
The Journal of Nutrition Jun 2004Certain nondigestible oligosaccharides can be selectively utilized by probiotics and reduce the risk of colon cancer. However, the inhibitory effects of...
Certain nondigestible oligosaccharides can be selectively utilized by probiotics and reduce the risk of colon cancer. However, the inhibitory effects of xylooligosaccharides (XOS) on colon cancer are not well documented. This study evaluated the effects of xylooligosaccharides and fructooligosaccharides (FOS) on the alteration of cecal microbiota, cecal pH, cecal weight, and serum lipid levels, and also their inhibitory effect on precancerous colon lesions in male Sprague-Dawley rats. The rats were randomly assigned to 4 groups: control, treatment with 1,2-dimethylhydrazine (DMH) [15 mg/(kg body wt.wk) for 2 wk], treatment with DMH + 60 g XOS/kg diet, and treatment with DMH + 60 g FOS/kg diet. Rats were fed the experimental diets for 35 d, beginning 1 wk after the second dose of DMH. Both XOS and FOS markedly decreased the cecal pH and serum triglyceride concentration, and increased the total cecal weight and bifidobacteria population. XOS had a greater effect on the bacterial population than did FOS. Moreover, both XOS and FOS markedly reduced the number of aberrant crypt foci in the colon of DMH-treated rats. These results suggest that XOS and FOS dietary supplementation may be beneficial to gastrointestinal health, and indicate that XOS is more effective than FOS.
Topics: 1,2-Dimethylhydrazine; Animals; Bifidobacterium; Carcinogens; Cecum; Colonic Diseases; Colony Count, Microbial; Hydrogen-Ion Concentration; Male; Oligosaccharides; Organ Size; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Triglycerides; Xylans
PubMed: 15173423
DOI: 10.1093/jn/134.6.1523 -
British Journal of Cancer Nov 1974Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes...
Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1-dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2-dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.
Topics: Animals; Colonic Neoplasms; Dimethylhydrazines; Endoplasmic Reticulum; Hydrazines; Kidney Neoplasms; Lethal Dose 50; Leucine; Liver; Male; Mice; Mitochondria; Monomethylhydrazine; Neoplasms; Neoplasms, Experimental; Rats; Ribosomes
PubMed: 4469195
DOI: 10.1038/bjc.1974.217 -
Toxicology and Applied Pharmacology Sep 1964
Topics: 1,2-Dimethylhydrazine; Amino Acids; Aspartate Aminotransferases; Blood; Brain Chemistry; Creatine; Creatinine; Dimethylhydrazines; Glutathione; Hydrazines; Liver; Metabolism; Rats; Research; Seizures; Sulfhydryl Compounds; Toxicology; Urine
PubMed: 14216997
DOI: 10.1016/0041-008x(64)90088-2 -
World Journal of Gastroenterology Jul 2014To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.
AIM
To investigate the effect of a high-fat diet in the formation of the precursors of colorectal cancer using an animal model.
METHODS
Wistar rats were divided into two groups that were fed either a high-fat diet (HFD) or a normal-fat diet (ND), and 1,2-dimethylhydrazine was administered at a dose of 40 mg/kg for 10 wk. The body weight/liver weight/epididymal fat weight were recorded after rats were sacrificed, and the formation of colonic adenoma was also observed. The levels of insulin, leptin, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1 and triglycerides were determined by enzyme-linked immunosorbent assay in order to compare the altered levels of biochemical indices and inflammatory cytokines in the serum between rats fed an ND and HFD. Cell proliferation activity (Ki-67) was determined by immunohistochemical analysis. Western blot and immunofluorescence staining were used to examine the expression of proliferating cell nuclear antigen (PCNA), cyclooxygenase (COX)-2, cyclin D1, β-catenin and nuclear factor (NF)-κB proteins in the adenoma and comparative control tissues.
RESULTS
The number of colonic adenomas and the colonic epithelial Ki-67 were significantly higher in the HFD group than in the ND group. The HFD group also had increased body weight, liver weight and epididymal fat weight, which were associated with increased levels of serum insulin, leptin, TNF-α, IGF-1 and triglycerides. HFD induced upregulation of PCNA, COX-2, cyclin D1, β-catenin and NF-κB proteins, as revealed by Western blot and immunofluorescence staining.
CONCLUSION
HFD promotes the formation of colonic adenoma through inflammation, metabolic abnormalities, and increases cell cycle progression.
Topics: 1,2-Dimethylhydrazine; Adenoma; Adiposity; Animals; Biomarkers, Tumor; Cell Cycle; Cell Proliferation; Colon; Colonic Neoplasms; Diet, High-Fat; Inflammation Mediators; Male; Neoplasms, Experimental; Rats, Wistar; Time Factors; Weight Gain
PubMed: 25009384
DOI: 10.3748/wjg.v20.i25.8119 -
Molecular Carcinogenesis Apr 2003There is growing interest in beta-catenin and its role in various human cancers. We recently reported that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and...
Mutational analysis of Ctnnb1 and Apc in tumors from rats given 1,2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline: mutational 'hotspots' and the relative expression of beta-catenin and c-jun.
There is growing interest in beta-catenin and its role in various human cancers. We recently reported that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and 1,2-dimethylhydrazine (DMH)-induced colon tumors in the rat contain mutations in Ctnnb1, the gene for beta-catenin, but the mutation spectrum was influenced by postinitiation exposure to chlorophyllin (CHL) and indole-3-carbinol (I3C) [Blum et al., Carcinogenesis 2001;22:315-320]. The present paper describes a follow-up study in which all of the target organs for IQ- and DMH-induced tumorigenesis were screened; Ctnnb1 mutations were found in 44 of 119 DMH-induced colon tumors, six of 13 IQ-induced colon tumors, 28 of 81 DMH-induced small intestine tumors, none of five IQ-induced small intestine tumors, four of 106 IQ-induced liver tumors, none of 14 DMH-induced Zymbal's gland tumors, none of 24 IQ-induced Zymbal's gland tumors, and none of 29 IQ-induced skin tumors. In tumors from rats given carcinogen alone, or carcinogen plus CHL or I3C, Ctnnb1 mutations frequently substituted amino acids adjacent to Ser33, a critical Ser/Thr residue in the glycogen synthase kinase-3beta regulatory domain of beta-catenin. However, substitution of critical Ser/Thr residues themselves was detected in only three of 24 (12.5%) of the tumors from rats given carcinogen alone, compared with 23 of 58 (40%) of the tumors from rats given carcinogen and treated postinitiation with I3C or CHL (P < 0.02). More than 50 of the colon tumors with wild-type beta-catenin were examined further for their Apc status; the overall frequency of Apc mutations was <10%, and these genetic changes occurred exclusively in the 'Mutation Cluster Region' of Apc. A subset of colon tumors also was examined for expression of beta-catenin and c-jun; these proteins were overexpressed in all tumors containing Ctnnb1 mutations, but the expression was highest in tumors with Ctnnb1 mutations affecting Thr41 and Ser45 residues in the glycogen synthase kinase-3beta region of beta-catenin. Thus, Ctnnb1 mutations occurred more frequently than Apc mutations in colon and small intestine tumors of the rat, and certain mutations upregulated beta-catenin/T-cell factor target genes more effectively than others, perhaps influencing the response to phytochemicals administered postinitiation.
Topics: 1,2-Dimethylhydrazine; Animals; Base Sequence; Carcinogens; Codon; Colonic Neoplasms; Consensus Sequence; Cytoskeletal Proteins; DNA Mutational Analysis; Genes, APC; Genes, jun; Intestinal Neoplasms; Liver Neoplasms; Male; Polymorphism, Single Nucleotide; Quinolines; Rats; Rats, Inbred F344; Skin Neoplasms; Trans-Activators; beta Catenin
PubMed: 12669311
DOI: 10.1002/mc.10112 -
Journal of Cancer Research and... 2016Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess...
AIM
Metallothionein (MT) is a small protein with a high affinity for divalent heavy metals and has a function in zinc homeostasis. The purpose of this study was to assess the MT mRNA gene expression as well as the MT protein content by immunohistochemistry and radioimmunoassay (RIA) in 1,2-dimethylhydrazine (DMH)-induced precancerous and cancerous colonic tissue in rats.
MATERIALS AND METHODS
Six-week-old rats were given subcutaneous injections of DMH twice a week for 3 months and sacrificed at 4 months (precancerous model) and 6 months (cancerous model). We determined MT mRNA expression by reverse transcription polymerase chain reaction and MT protein content by both immunohistochemical expression and cadmium-109 RIA.
RESULTS
MT mRNA expression in the large intestine showed statistically significant decrease in the precancerous (P < 0.01) and the cancerous (P < 0.001) model as compared with controls. Immunohistochemical expression of MT showed statistically significant decrease (P < 0.05) in the colonic cancerous tissue. MT content in the large intestine showed statistically significant decrease in precancerous (P < 0.005) and cancerous (P < 0.001) model as compared with controls.
CONCLUSION
This study suggests that a decrease in the colonic MT mRNA expression, MT protein expression, and content in DMH-induced colonic cancer model is associated with the development of preneoplastic lesions and further progression to carcinoma in the colon results in a greater reduction in the levels of each of these parameters.
Topics: 1,2-Dimethylhydrazine; Animals; Colonic Neoplasms; Gene Expression; Immunohistochemistry; Metallothionein; Precancerous Conditions; RNA, Messenger; Rats
PubMed: 28169244
DOI: 10.4103/0973-1482.179107 -
Nutrients Aug 2021Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural...
BACKGROUND
Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural fiber-rich food product (NFRFP) and to evaluate its safety, toxicogenetics, and effects on aberrant crypt foci induced by 1,2-dimethyl-hydrazine in a preclinical model.
METHODS
A total of 78 male Wistar rats were distributed in six experimental groups: negative control, positive control (1,2-Dimethylhydrazine-40 mg/Kg), and four groups fed with 10% NFRFP: NFRFP, pre-treatment protocol, simultaneous treatment, and post-treatment protocol.
RESULTS
The NFRFP was shown to be a good source of fibers and did not change biometric, biochemical, hematological, and inflammatory parameters, and did not induce signs of toxicity and genotoxicity/carcinogenicity. NFRFP exhibited a chemopreventive effect, in all protocols, with damage reduction (% DR) of 75% in the comet test. NFRFP reduced the incidence of aberrant crypt outbreaks by 49.36% in the post-treatment protocol.
CONCLUSIONS
The results suggest the applicability of NFRFP in the human diet due to potential production at an industrial scale and easy technological application in different products, since it could be incorporated in food without altering or causing small changes in final product sensory characteristics.
Topics: 1,2-Dimethylhydrazine; Aberrant Crypt Foci; Animal Feed; Animals; Colon; Colorectal Neoplasms; Cytokines; Dietary Fiber; Disease Models, Animal; Inflammation Mediators; Male; Rats, Wistar; Rats
PubMed: 34444868
DOI: 10.3390/nu13082708 -
Neurobiology of Aging Jul 2018We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data...
We previously reported a granulin (GRN) null mutation, originating from a common founder, in multiple Belgian families with frontotemporal dementia. Here, we used data of a 10-year follow-up study to describe in detail the clinical heterogeneity observed in this extended founder pedigree. We identified 85 patients and 40 unaffected mutation carriers, belonging to 29 branches of the founder pedigree. Most patients (74.4%) were diagnosed with frontotemporal dementia, while others had a clinical diagnosis of unspecified dementia, Alzheimer's dementia or Parkinson's disease. The observed clinical heterogeneity can guide clinical diagnosis, genetic testing, and counseling of mutation carriers. Onset of initial symptomatology is highly variable, ranging from age 45 to 80 years. Analysis of known modifiers, suggested effects of GRN rs5848, microtubule-associated protein tau H1/H2, and chromosome 9 open reading frame 72 GC repeat length on onset age but explained only a minor fraction of the variability. Contrary, the extended GRN founder family is a valuable source for identifying other onset age modifiers based on exome or genome sequences. These modifiers might be interesting targets for developing disease-modifying therapies.
Topics: Adult; Age of Onset; Aged; Aged, 80 and over; Belgium; Dimethylhydrazines; Female; Follow-Up Studies; Frontotemporal Dementia; Genetic Association Studies; Humans; Intercellular Signaling Peptides and Proteins; Loss of Function Mutation; Male; Middle Aged; Pedigree; Progranulins; Propionates
PubMed: 29653316
DOI: 10.1016/j.neurobiolaging.2018.03.007