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Asian Pacific Journal of Cancer... Oct 2023Much research has been conducted to identify natural antioxidant and antimutagenic compounds capable of preventing, reverting or treating conditions caused by oxidative...
OBJECTIVE
Much research has been conducted to identify natural antioxidant and antimutagenic compounds capable of preventing, reverting or treating conditions caused by oxidative stress and genotoxicity. In this study we evaluated the effects of 10% gum arabic (GA) and eugenol (EUG) on hepatic oxidative stress and genotoxicity induced by dimethylhydrazine (DMH) in rats.
METHODS
The prevention arm of the study included 4 control groups and 4 experimental groups. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA , EUG or 10% GA + EUG by gavage. The treatment arm of the study included 4 control groups and 4 experimental groups. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. Finally, the livers were harvested for histopathological study with HE, measurement of genotoxicity and oxidative stress.
RESULT
Genotoxicity and oxidative stress were found to be significantly lower in Group XII (animals treated concomitantly with GA and EUG). This is the first study to observe the synergistic action of GA and EUG administered concomitantly in this scenario.
CONCLUSION
Indicating a synergistic antigenotoxic and antioxidant effect on liver cells in rats with DMH-induced colorectal carcinogenesis.
Topics: Rats; Animals; Antioxidants; Eugenol; Gum Arabic; Rats, Wistar; Colonic Neoplasms; 1,2-Dimethylhydrazine; Carcinogenesis; Liver; Water
PubMed: 37898850
DOI: 10.31557/APJCP.2023.24.10.3447 -
Oxidative Medicine and Cellular... 2022This study was conducted among 60 rats, and groups consist of control, three separate groups for RJ, dimethylhydrazine (DMH), and vitamin E, and two separate treated...
METHODS
This study was conducted among 60 rats, and groups consist of control, three separate groups for RJ, dimethylhydrazine (DMH), and vitamin E, and two separate treated groups with DMH + RJ and DMH + vitamin E. Additionally, the cytotoxicity of royal jelly was examined on HT-29 cell line. . Based on the assessment using MTT assay, the LC50 of royal jelly was 1.781 mg/ml, and the highest cytotoxicity was observed at 25 mg/ml concentration after 48 hours. Meanwhile, in the study, after the 13th week, compared to the DMH group, the rats exposed to DMH + royal jelly experienced a significant less oxidative stress ( < 0.05) and a significantly greater total antioxidant capacity (TAC) level ( < 0.05). The expression of proliferating cell nuclear antigen (PCNA), platelet-derived growth factor (PDGF), and carcinoembryonic antigen (CEA) proteins significantly decreased among the animals receiving DMH + royal jelly compared to the DMH group. The pathological examinations revealed less congestion, necrosis, inflammation, and cell proliferation in the colon tissue of the RJ-treated group than that of the DMH group. Overall, the biochemical indices were better in the treatment groups in comparison with the DMH group.
CONCLUSION
The results represented the clinical usability of royal jelly, as a substance with anticancer properties, to prevent and treat colorectal cancer. This issue is related to its effective antioxidant potential, which even exhibits more effectiveness than the vitamin E, which is known as a strong antioxidant.
Topics: Animals; Rats; 1,2-Dimethylhydrazine; Antineoplastic Agents; Antioxidants; Colonic Neoplasms; Colorectal Neoplasms; Fatty Acids; Rats, Wistar; Vitamin E
PubMed: 35910834
DOI: 10.1155/2022/9506026 -
Folia Morphologica 2021Colon cancer is considered to be the third most common cancer worldwide. At diagnosis of colon cancer, 3.7-11% developed bone metastasis. Diet based strategies are...
BACKGROUND
Colon cancer is considered to be the third most common cancer worldwide. At diagnosis of colon cancer, 3.7-11% developed bone metastasis. Diet based strategies are important for prevention and treatment of colon cancer. This study investigated the effect of vitamin B17 on a DMH induced rat model of colon cancer.
MATERIALS AND METHODS
Eighty young adult male albino rats were divided into five groups: group I (control group), group II (vitamin B17), group III (colon cancer), group IV (protected) and group V (treated). Distal colon sections were prepared for light and scanning electron microscopic examination. Lumbar vertebrae specimens were prepared for light microscopic study. Morphometric and statistical analysis were done.
RESULTS
In comparison with the control, both colon cancer and treated groups showed invasion of the colonic tissue by pleomorphic branching colonic glands of variable shapes and sizes lined with dysplastic elongated hyperchromatic nuclei with frequent mitotic figures or stratified multi-layered crowded nuclei with an extremely significant (p < 0.0001) reduction of goblet cell number when compared to the control together with major pathological bone changes were observed in colon cancer and the treated groups.
CONCLUSIONS
While the protected group showed impressive improvement of all previously mentioned diameters.
Topics: 1,2-Dimethylhydrazine; Animals; Colonic Neoplasms; Male; Rats; Vitamins
PubMed: 32073131
DOI: 10.5603/FM.a2020.0021 -
Journal of Veterinary Science 2013Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary... (Randomized Controlled Trial)
Randomized Controlled Trial
Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFκB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of β-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFκB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFα, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development.
Topics: Animals; Bacterial Proteins; Colon; Colonic Neoplasms; Colony Count, Microbial; Cyclooxygenase 2; Cytokines; Diet; Dietary Supplements; Dimethylhydrazines; Enterobacteriaceae; Fatty Acids, Volatile; Female; Gene Expression Regulation; Inulin; Lactobacillaceae; Male; NF-kappa B; Prebiotics; Rats; Rats, Sprague-Dawley
PubMed: 23820222
DOI: 10.4142/jvs.2013.14.4.387 -
The Turkish Journal of Gastroenterology... Jul 2018The aim of this study was to investigate the influence of a synbiotic preparation (a mixture of six probiotics and a prebiotic) on aberrant crypt foci (ACF) formation,...
BACKGROUND/AIMS
The aim of this study was to investigate the influence of a synbiotic preparation (a mixture of six probiotics and a prebiotic) on aberrant crypt foci (ACF) formation, dysplasia, inflammation, and colitis-like lesions in experimental colon cancer in rats.
MATERIALS AND METHODS
Sixty male rats were categorized into three groups of 20 animals each. Group A was administered 1,2-dimethylydrazine, 15 mg/kg body weight (BW), once a week for 2 weeks. Group B was administered 1,2-dimethylydrazine at the same dose plus synbiotic, started after the second dose of carcinogen and lasted for 5 weeks. Group C was administered synbiotic plus carcinogen from the beginning of the experiment and lasted for 7 weeks. Animals were killed at the end of week 7.
RESULTS
At the end of the experiment, the animals that received carcinogen plus the synbiotic had 100%, whereas the animals that received only carcinogen has 70% survival. Animals of groups B and C had significantly lower percentage of inflammation, colitis-like lesions, and ACF dysplasia than animals of group A, whereas those of group C had the least pathological lesions.
CONCLUSION
Synbiotics seem to protect against the appearance of preneoplastic colon lesions in rats. The results of this experimental study suggest that treatment with a synbiotic preparation exerts significant antimutagenic properties against the development of preneoplastic lesions in rats.
Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Carcinogens; Colon; Colonic Neoplasms; Male; Precancerous Conditions; Rats; Synbiotics
PubMed: 30249566
DOI: 10.5152/tjg.2018.17469 -
Cellular Physiology and Biochemistry :... 2018Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential...
BACKGROUND/AIMS
Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats.
METHODS
The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, β-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups.
RESULTS
The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, β-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities.
CONCLUSION
Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, β-catenin, and MDR-1 genes and enhancing the antioxidant activity.
Topics: 1,2-Dimethylhydrazine; ATP Binding Cassette Transporter, Subfamily B, Member 1; Aberrant Crypt Foci; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Catalase; Colon; Colonic Neoplasms; Down-Regulation; Glutathione; Lipid Peroxidation; Male; Mice; Microtubule-Associated Proteins; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Survivin; beta Catenin
PubMed: 29439258
DOI: 10.1159/000487349 -
World Journal of Gastroenterology Mar 2015To investigate angiopoietin (Ang) and vascular endothelial growth factor (VEGF) expression in rats with ulcerative colitis (UC) and colorectal cancer (CRC).
AIM
To investigate angiopoietin (Ang) and vascular endothelial growth factor (VEGF) expression in rats with ulcerative colitis (UC) and colorectal cancer (CRC).
METHODS
Dysplasia and cancer were investigated in rats that received three cycles of 3.5% dextran sulfate sodium (DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine (DMH) (CRC group). Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline (UC group). Rats without DSS or DMH treatment served as controls. Expression of the tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2 and its ligands, Ang-1 and Ang-2, as well as VEGF were evaluated in the colorectum by Western blotting.
RESULTS
Compared with rats in the control group, rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea, rectal bleeding, wasting, and loss of body weight (P < 0.05). In addition, the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats (8.29 ± 0.21 and 8.31 ± 0.86, respectively, vs 12.34 ± 0.12 cm; P < 0.05). Furthermore, rats in the CRC group, but not in the UC or control groups, developed multiple tumors in the colorectal region. Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1, Ang-2, Tie-2, and VEGF in the colorectum compared to rats in the control group.
CONCLUSION
Increased expression of Ang-1, Ang-2, Tie-2, and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.
Topics: 1,2-Dimethylhydrazine; Angiopoietin-1; Angiopoietin-2; Animals; Colitis, Ulcerative; Colon; Colorectal Neoplasms; Dextran Sulfate; Disease Models, Animal; Male; Rats, Wistar; Receptor, TIE-2; Up-Regulation; Vascular Endothelial Growth Factor A
PubMed: 25759532
DOI: 10.3748/wjg.v21.i9.2645 -
World Journal of Gastroenterology Aug 2011To investigate colorectal uptake of solid lipid nanoparticles (SLNs) in mice receiving different doses of 1,2-dimethylhydrazine (DMH) using magnetic resonance (MR) and...
AIM
To investigate colorectal uptake of solid lipid nanoparticles (SLNs) in mice receiving different doses of 1,2-dimethylhydrazine (DMH) using magnetic resonance (MR) and laser-scanning confocal fluorescence microscope (LSCFM) imaging.
METHODS
Eight mice were sacrificed in a pilot study to establish the experimental protocol and to visualize colorectal uptake of SLNs in normal mice. Gadopentetate dimeglumine and fluorescein isothiocyanate (FITC)-loaded SLN (Gd-FITC-SLN) enemas were performed on mice receiving DMH for 10 wk (group 1, n = 9) or 16 wk (group 2, n = 7) and FITC-SLN enema was performed on 4 DMH-treated mice (group 3). Pre- and post-enema MR examinations were made to visualize the air-inflated distal colorectum. Histological and LSCFM examinations were performed to verify colorectal malignancy and to track the distribution of SLNs.
RESULTS
Homogeneous enhancement and dense fluorescence (FITC) deposition in colorectal wall were observed in normal mice and 1 DMH-treated mouse (group 1) on fluid attenuated inversion recovery (FLAIR) and LSCFM images, respectively. Heterogeneous mural enhancement was found in 6 mice (4 in group 1; 2 in group 2). No visible mural enhancement was observed in the other mice. LSCFM imaging revealed linear fluorescence deposition along the colorectal mucosa in all groups. Nine intraluminal masses and one prolapsed mass were detected by MR imaging with different enhancement modes and pathologies. Interstitial FITC deposition was identified where obvious enhancement was observed in FLAIR images. Bladder imaging agent accumulations were observed in 11 of 16 DMH-treated mice of groups 1 and 2.
CONCLUSION
There are significant differences in colorectal uptake and distribution of SLNs between normal and DMH-treated mice, which may provide a new mechanism of contrast for MR colonography.
Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Carcinogens; Colon; Colorectal Neoplasms; Enema; Fluorescein; Fluorescent Dyes; Magnetic Resonance Imaging; Male; Mice; Microscopy, Confocal; Nanoparticles; Pilot Projects; Rectum
PubMed: 21987608
DOI: 10.3748/wjg.v17.i31.3614 -
PloS One 2011Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet...
BACKGROUND AND AIM
Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice.
METHODS
For gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software.
RESULTS
The tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes.
CONCLUSION
In the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.
Topics: 1,2-Dimethylhydrazine; Animals; Basic-Leucine Zipper Transcription Factors; Calcium; Calgranulin B; Colorectal Neoplasms; Disease Models, Animal; Female; Forkhead Box Protein M1; Forkhead Transcription Factors; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Matrix Metalloproteinase 10; Mice; Mice, Inbred ICR; NF-kappa B; Oligonucleotide Array Sequence Analysis; Period Circadian Proteins; Peroxiredoxin VI; Real-Time Polymerase Chain Reaction; Ribonuclease, Pancreatic
PubMed: 21857934
DOI: 10.1371/journal.pone.0022566 -
Mutation Research. Genetic Toxicology... Jul 2015As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods...
As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals.
Topics: 1,2-Dimethylhydrazine; 2-Acetylaminofluorene; Administration, Oral; Aniline Compounds; Animals; Arsenites; Carcinogens; Comet Assay; DNA Damage; DNA Fragmentation; Dimethylnitrosamine; Dose-Response Relationship, Drug; Liver; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sodium Chloride; Sodium Compounds; Stomach
PubMed: 26212309
DOI: 10.1016/j.mrgentox.2015.03.003