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Asian Pacific Journal of Cancer... Apr 2024The aim of this study is to examine the M1 and M2 macrophages distribution in the rat's colon of DMH-induced inflammation associated colorectal cancer.
OBJECTIVE
The aim of this study is to examine the M1 and M2 macrophages distribution in the rat's colon of DMH-induced inflammation associated colorectal cancer.
METHODS
Colon tissue of three groups of 4 rats that induced using 1,2 dimethylhydrazine (DMH) at 30 mg/kg bw every week for 9, 11, and 13 weeks were used. The M1 and M2 distribution was examined by using antibody anti iNOS for M1 and anti-CD163 for M2 with immunohistochemistry method. The data was presents in figure and table in the form of percentage.
RESULT
M1 macrophage was found in all groups in the low distribution level (25% - 50%), while M2 macrophage was observed in all groups with 100% distribution. In the longer period of DMH induction, M2 macrophages was distributed more abundant.
CONCLUSION
All of the rat's colon showing chronic inflammation that led to the tumorigenesis.
Topics: Animals; Rats; Colorectal Neoplasms; Macrophages; 1,2-Dimethylhydrazine; Inflammation; Colon; Male; Nitric Oxide Synthase Type II; Antigens, Differentiation, Myelomonocytic; Antigens, CD; Carcinogens; Receptors, Cell Surface
PubMed: 38679997
DOI: 10.31557/APJCP.2024.25.4.1357 -
Asian Pacific Journal of Cancer... Feb 2024The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons.
OBJECTIVE
The study's aim was to evaluate Brazilian Brown Propolis (BBP) and Artepillin C (ARC) chemopreventive action in Wistar rats' colons.
METHODS
Fifty male Wistar rats were divided into ten experimental groups, including control groups, groups with and without 1,2-dimethylhydrazine (DMH) induction, and BBP, ARC, and ARC enriched fraction (EFR) treatments, for sixteen weeks. Aberrant crypt foci (ACF) were classified as hyperplastic or dysplastic, and proliferating cell nuclear antigen (PCNA) expression was quantified.
RESULT
ACF amounts in experimental groups (induced or not) decreased in both colon portions, while the isolated Aberrant Crypt (AC) number increased. Experimental groups of animals showed higher hyperplasia and dysplasia amounts compared with control groups. The ACF dysplastic amount present in groups induced and treated, in both colon portions, had similar values to IDMH (DMH induction group without treatment). In addition, DMH was effective in ACF inducing and there was positive staining for PCNA in basal and upper dysplastic foci portions in all experimental groups, in the mitotic index (MI) evaluation. To conclude, considering all the experimental groups, the one treated with EFR (fraction enriched with ARC) had the lowest rates of cell proliferation.
CONCLUSION
BBP and its derivatives prevented crypt cell clonal expansion.
Topics: Rats; Animals; Male; Rats, Wistar; Colonic Neoplasms; Proliferating Cell Nuclear Antigen; Propolis; 1,2-Dimethylhydrazine; Brazil; Aberrant Crypt Foci; Antineoplastic Agents; Carcinogens; Phenylpropionates
PubMed: 38415543
DOI: 10.31557/APJCP.2024.25.2.563 -
Journal of Traditional Chinese Medicine... Feb 2024To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the...
Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model.
OBJECTIVE
To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the 1,2-Dimethylhydrazine (DMH)/dextran sodium sulphate (DSS)-induced mouse model.
METHODS
Institute of cancer research (ICR) male mice were injected with 20 mg/kg DMH for a week. After that, 2% DSS was administered in the drinking water for another 7 d. The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice. Histopathological examination was used for observing the CRC development at colonic mucosa. Immunohistochemistry (IHC), blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC. The reversing targets searching method was applied with artificial intelligence (AI), computer-aided drug designing (CADD) and Ingenuity Pathway Analysis (IPA) techniques for predicting the potential targets and mechanism of CADPE highly related to CRC.
RESULTS
The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment. CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development. Finally, our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) in two major cancer development pathways.
CONCLUSIONS
CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR, ERK and mTOR activities in two highly related CRC developing pathways.
Topics: Mice; Male; Animals; 1,2-Dimethylhydrazine; Dextrans; Artificial Intelligence; Colorectal Neoplasms; Signal Transduction; Inflammation; ErbB Receptors; TOR Serine-Threonine Kinases; Mammals; Caffeic Acids; Sulfates
PubMed: 38213241
DOI: 10.19852/j.cnki.jtcm.20231204.001 -
International Journal of Molecular... Dec 2023"Heptil" (unsymmetrical dimethylhydrazine-UDMH) is extensively employed worldwide as a propellant for rocket engines. However, UDMH constantly loses its properties as a... (Review)
Review
The Recycling of Substandard Rocket Fuel N,N-Dimethylhydrazine via the Involvement of Its Hydrazones Derived from Glyoxal, Acrolein, Metacrolein, Crotonaldehyde, and Formaldehyde in Organic Synthesis.
"Heptil" (unsymmetrical dimethylhydrazine-UDMH) is extensively employed worldwide as a propellant for rocket engines. However, UDMH constantly loses its properties as a result of its continuous and uncontrolled absorption of moisture, which cannot be rectified. This situation threatens its long-term usability. UDMH is an exceedingly toxic compound (Hazard Class 1), which complicates its transportation and disposal. Incineration is currently the only method used for its disposal, but this process generates oxidation by-products that are even more toxic than the original UDMH. A more benign approach involves its immediate reaction with a formalin solution to form 1,1-dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding substantial amounts of nitrogen oxides. This review seeks to shift the focus of MDH from incineration towards its application in the synthesis of relatively non-toxic and readily available analogs of various pharmaceutical substances. We aim to bring the attention of the international chemical community to the distinctive properties of MDH, as well as other hydrazones (such as glyoxal, acrolein, crotonal, and meta-crolyl), wherein each structural fragment can initiate unique transformations that have potential applications in molecular design, pharmaceutical research, and medicinal chemistry.
Topics: Acrolein; Glyoxal; Dimethylhydrazines; Formaldehyde; Chemistry Techniques, Synthetic
PubMed: 38139025
DOI: 10.3390/ijms242417196 -
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 -
Biomedicine & Pharmacotherapy =... Sep 2023Dichloromethane extract of Cleistocalyx nervosum var. paniala seeds exhibited an anticarcinogenicity against chemically-induced the early stages of carcinogenesis in...
2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone from Cleistocalyx nervosum var. paniala seeds attenuated the early stage of diethylnitrosamine and 1,2-dimethylhydrazine-induced colorectal carcinogenesis.
BACKGROUND
Dichloromethane extract of Cleistocalyx nervosum var. paniala seeds exhibited an anticarcinogenicity against chemically-induced the early stages of carcinogenesis in rats. This study aimed to identify anticarcinogenic compounds from C. nervosum seed extract (CSE).
METHODS
Salmonella mutation assay was performed to determine mutagenicity and antimutagenicity of partially purified and purified compounds of CSE. The anticarcinogenic enzyme-inducing activity was measured in Hepa1c1c7. Moreover, the anticancer potency was examined on various human cancer cell lines. The anticarcinogenicity of DMC was investigated using dual-organ carcinogenicity model. The number of preneoplastic lesions was evaluated in the liver and colon. The inhibitory mechanisms of DMC on liver- and colorectal carcinogenesis were investigated.
RESULTS
Six partially purified fractions (MK1 - MK6) and purified compounds, including 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) and hariganetin, were obtained from CSE. Among these fractions, MK4 and DMC presented the greatest antimutagenicity against indirect mutagens in bacterial model. Moreover, MK5 possessed an effective anticarcinogenic enzyme inducer in Hepa1c1c7. The MK4, DMC and CSE showed greater anticancer activity on all cell lines and exhibited the most effective toxicity on colon cancer cells. Furthermore, DMC inhibited the formation of colonic preneoplastic lesions in carcinogens-treated rats. It reduced PCNA-positive cells and frequency of BCAC in rat colon. DMC also enhanced the detoxifying enzyme, GST, in rat livers.
CONCLUSIONS
DMC obtained from CSE may be a promising cancer chemopreventive compound of colorectal cancer process in rats. It could increase detoxifying enzymes and suppress the cell proliferation process resulting in prevention of post-initiation stage of colorectal carcinogenesis.
Topics: Humans; Rats; Animals; Syzygium; Diethylnitrosamine; 1,2-Dimethylhydrazine; Seeds; Carcinogenesis; Colorectal Neoplasms
PubMed: 37517291
DOI: 10.1016/j.biopha.2023.115221 -
Indian Journal of Pharmacology 2023Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the...
OBJECTIVES
Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems.
MATERIALS AND METHODS
The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis.
RESULTS
The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation.
CONCLUSIONS
These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.
Topics: Humans; Male; Animals; Rats; Rats, Wistar; 1,2-Dimethylhydrazine; Tumor Suppressor Protein p53; bcl-2-Associated X Protein; Caspase 3; Colonic Neoplasms; Antioxidants; Carcinoma; Tumor Microenvironment
PubMed: 37313935
DOI: 10.4103/ijp.ijp_168_22 -
International Journal of Molecular... Mar 2023Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. is a...
Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.
Topics: Rats; Animals; Rats, Sprague-Dawley; Andrographis paniculata; 1,2-Dimethylhydrazine; Diet, High-Fat; Plant Extracts; Colonic Neoplasms; Anticarcinogenic Agents; Obesity; Aberrant Crypt Foci; Carcinogens
PubMed: 36982300
DOI: 10.3390/ijms24065224 -
BioMed Research International 2022Cancer is one of the leading causes of death worldwide, and natural agents have shown some promise in fighting it. Thus, the present study tried to evaluate the healing...
Cancer is one of the leading causes of death worldwide, and natural agents have shown some promise in fighting it. Thus, the present study tried to evaluate the healing potential of an equal combination of olive and sesame extract (MOS) against the colorectal cancerous lesions that were induced by dimethylhydrazine (DMH) in male rats and also compare the anticarcinogenic potential of the MOS and vitamin E with each other. Therefore, the mixture of equal olive and sesame extract (MOS) was used as the main treatment, alongside vitamin E as a parallel treatment. This study examined the red blood cell (RBC) and white blood cell (WBC) levels, biochemical indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), albumin, and the colon tissue pathology, as well as the level of protein expression of the adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF). Also, the tissue stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were analyzed. Overall, the results represented a significant reduction in the congestion, mitotic index, inflammation, and cell destruction in the MOS group compared to the DMH group. In terms of the oxidative stress level, a significant increase was observed in the DMH group in comparison with the DMH-MOS group ( < 0.05), and the MOS significantly increased TAC level ( < 0.05). Furthermore, the DMH+MOS-exposed group exhibited a significantly lower expression of the PCNA, CEA, and PDGF proteins than those of the DMH group. Overall, the MOS showed that it can effectively prevent DMH-induced colon lesions. This mixture, as a strong antioxidant agent, can be clinically applied for preventing and treating colorectal cancer, the effectiveness of which is higher than that of vitamin E.
Topics: Animals; Male; Rats; 1,2-Dimethylhydrazine; Antioxidants; C-Reactive Protein; Carcinoembryonic Antigen; Colorectal Neoplasms; Creatine Kinase; Lactate Dehydrogenases; Malondialdehyde; Olea; Platelet-Derived Growth Factor; Proliferating Cell Nuclear Antigen; Rats, Wistar; Sesamum; Superoxide Dismutase; Vitamin E
PubMed: 36262974
DOI: 10.1155/2022/5440773 -
Scientific Reports Sep 2022Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of...
Ficus dubia latex extract prevent DMH-induced rat early colorectal carcinogenesis through the regulation of xenobiotic metabolism, inflammation, cell proliferation and apoptosis.
Ficus dubia latex is recognized as a remedy in Asian traditional medicine with various therapeutic effects. The present study aimed to determine the preventive action of Ficus dubia latex extract (FDLE) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis and its mechanisms. The experiment included an initiation model in which rats were orally administered with FDLE daily for 1 week before DMH injection until the end of the experiment, while only after DMH injection until the end in the post-initiation model. The results firstly indicated that FDLE treatment could reduce the level of methylazoxymethanol (MAM) in rat colonic lumen by inhibition of the activities of both phase I xenobiotic metabolizing enzymes in the liver and β-glucuronidase in the colon, leading to reduced DNA methylation in colonic mucosal cells, related to the number of ACF in the initiation stage. Besides, FDLE modulated the inflammation which could suppress the growth and induce apoptosis of aberrant colonic mucosal cells, leading to retardation of ACF multiplicity. Therefore, FDLE showed the ability to suppress the DMH-induced rat ACF formation and inflammation promoted growth of ACF. In conclusion, FDLE had the potential to prevent carcinogens-induced rat colorectal carcinogenesis in the initiation stage.
Topics: Animals; Rats; 1,2-Dimethylhydrazine; Apoptosis; Carcinogenesis; Cell Proliferation; Colonic Neoplasms; Dimethylhydrazines; Ficus; Inflammation; Latex; Plant Extracts; Rats, Wistar; Xenobiotics
PubMed: 36104433
DOI: 10.1038/s41598-022-19843-9