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International Journal of Molecular... Apr 2018Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids,...
Resistant starch is as common soluble fiber that escapes digestion in the small intestine and can regulate intestinal function, metabolism of blood glucose and lipids, and may prevent tumorigenesis of gastrointestinal cancer. Epidemiology and other evidence have suggested that resistant starch may prevent colon cancer development. The aim of the current study was to explore the ameliorative effects and potential mechanisms of resistant starch in the tumorigenesis of colon tumors induced by dimethylhydrazine in C57BL/6 mice. Western blot analysis, ELISA, microscopy, immunofluorescence and immunohistochemistry were used to analyze the efficacy of resistant starch on the metabolic balance in the colon and tumorigenesis of colon tumors. The results demonstrated that a diet containing resistant starch decreased the animal body weight and reduced free ammonia, pH and short chain fatty acids in feces compared with mice that received a standard diet. Resistant starch reduced the incidence of colon tumors and suppressed the expression of carcinogenesis‑associated proteins, including heat shock protein 25, protein kinase C‑d and gastrointestinal glutathione peroxidase in colon epithelial cells compared with standard starch and control groups. Colon tumor cells proliferation and dedifferentiation were significantly decreased by a resistant starch diet. The results also demonstrated that resistant starch increased the apoptosis of colon tumor cells through regulation of apoptosis‑associated gene expression levels in colon tumor cells. Oxidative stress and endoplasmic reticulum stress were upregulated, and elevation eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor‑4 and secretase‑β expression levels were increased in the resistant starch diet group. Additionally, the activity of eIF2α and PERK were increased in colon tumor cells from mice that had received resistant starch. Increasing DNA damage‑inducible transcript 3 protein (CHOP), binding immunoglobulin protein (BIP) and caspase‑12 expression levels upregulated by resistant starch diet may contribute to the resistant starch‑induced apoptosis of colon tumor cells induced by 1,2‑dimethylhydrazine. In vitro assays demonstrated that knockdown of eIF2α inhibited apoptosis of colon tumor cells isolated from mice fed with resistant starch, which also downregulated CHOP, BIP and caspase‑3 expression levels compared with controls. Furthermore, long‑term survival of experimental mice was prolonged by the resistant starch diet compared with the standard diet group. In conclusion, the results indicate that resistant starch in the diet may prevent carcinogenesis of colon epithelial cells, mediated by enhancing apoptosis through an endoplasmic reticulum stress‑mediated mitochondrial apoptosis pathway.
Topics: Animals; Apoptosis; Body Weight; Carcinogenesis; Cell Line; Colon; Colonic Neoplasms; Diet; Dietary Fiber; Dimethylhydrazines; Endoplasmic Reticulum Stress; Mice, Inbred C57BL; Mitochondria; Signal Transduction; Starch; Tumor Cells, Cultured
PubMed: 29393371
DOI: 10.3892/ijmm.2018.3423 -
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 -
BioMed Research International 2022Propolis is a natural compound with anticarcinogenic properties. The present study aimed to compare the inhibitory effect of ethanolic extract of propolis (EEP) and...
Propolis is a natural compound with anticarcinogenic properties. The present study aimed to compare the inhibitory effect of ethanolic extract of propolis (EEP) and vitamin E on dimethylhydrazine-induced colon lesions in rats. In this study, 60 rats were randomly categorized into six 10-member groups. After 13 weeks, blood and colon tissue were sampled to examine some factors. The parameters included red (RBC) and white (WBC) blood cell profile, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), and albumin, as well as the extent of colon histological lesions, protein expression (adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF)), and oxidative stress markers (total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD)) in colon tissue. A significant decrease was observed in congestion, mitotic index, inflammation, and cell destruction in colon tissue in dimethylhydrazine group in comparison with the control group ( < 0.05). The EEP exposed rats exhibited a significant lower oxidative stress than the DMH group ( < 0.05). Furthermore, the extract significantly affected TAC level ( < 0.05). While the expression level of APC rose substantially in the EEP-treated group compared to the DMH group, the level of PCNA, CEA, and PDGF proteins significantly reduced. It seems that the EEP can efficiently prevent DMH-induced colonic lesions. Furthermore, its effectiveness is more than the vitamin E, which is a strong antioxidant.
Topics: Animals; Rats; Adenomatous Polyposis Coli; Antioxidants; Ascomycota; Carcinoembryonic Antigen; Dimethylhydrazines; Ethanol; Plant Extracts; Proliferating Cell Nuclear Antigen; Propolis; Rats, Wistar; Vitamin E
PubMed: 35782078
DOI: 10.1155/2022/8497562 -
International Journal of Molecular... Aug 2017The role of deficiency of oxoguanine glycosylase 1 () homolog, a repair enzyme of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) residue in DNA, was investigated using the...
The role of deficiency of oxoguanine glycosylase 1 () homolog, a repair enzyme of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) residue in DNA, was investigated using the multiorgan carcinogenesis bioassay in mice. A total of 80 male and female six-week-old mice of C57BL/6J background carrying a mutant allele of the gene () and wild type (Ogg1) mice were administered N-diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), N-bis (2-hydroxypropyl) nitrosamine (DHPN) and 1,2-dimethylhydrazine dihydrochloride (DMH) (DMBDD) to induce carcinogenesis in multiple organs, and observed up to 34 weeks. Significant increase of lung adenocarcinomas incidence was observed in DMBDD-treated male mice, but not in DMBDD-administered animals. Furthermore, incidences of lung adenomas were significantly elevated in both males and females as compared with respective control and DMBDD-treated groups. Incidence of total liver tumors (hepatocellular adenomas, hemangiomas and hemangiosarcomas) was significantly higher in the DMBDD-administered males and females. In addition, in DMBDD-treated male mice, incidences of colon adenomas and total colon tumors showed a trend and a significant increase, respectively, along with significant rise in incidence of simple hyperplasia of the urinary bladder, and a trend to increase for renal tubules hyperplasia in the kidney. Furthermore, incidence of squamous cell hyperplasia in the forestomach of DMBDD-treated male mice was significantly higher than that of males. Incidence of small intestine adenomas in DMBDD groups showed a trend for increase, as compared to the wild type mice. The current results demonstrated increased susceptibility of mutant mice to the multiorgan carcinogenesis induced by DMBDD. The present bioassay could become a useful tool to examine the influence of various targets on mouse carcinogenesis.
Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Butylhydroxybutylnitrosamine; Carcinogenesis; Carcinogens; Carcinoma, Hepatocellular; DNA Glycosylases; Diethylnitrosamine; Female; Liver Neoplasms; Lung Neoplasms; Male; Methylnitrosourea; Mice, Inbred C57BL; Mice, Knockout; Mutation; Nitrosamines
PubMed: 28820464
DOI: 10.3390/ijms18081801 -
Canadian Journal of Physiology and... Jan 2012This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in...
Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF.
This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)(-1)) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced by [corrected] 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.
Topics: 1,2-Dimethylhydrazine; Aberrant Crypt Foci; Animals; Anticarcinogenic Agents; Antioxidants; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Drug Screening Assays, Antitumor; Free Radical Scavengers; Lipid Peroxidation; Male; Organic Chemicals; Rats; Rats, Wistar
PubMed: 22185381
DOI: 10.1139/y11-100 -
Experimental Physiology Sep 2020What is the central question of this study? What are the alleviative effects of the combination of exercise training and quercetin supplementation on colorectal...
Combination of quercetin and exercise training attenuates depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer: Possible involvement of inflammation and BDNF signalling.
NEW FINDINGS
What is the central question of this study? What are the alleviative effects of the combination of exercise training and quercetin supplementation on colorectal cancer-related depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer and what is the corresponding signalling pathway? What is the main finding and its importance? We showed that the combination of exercise training and quercetin supplementation resulted in a significant decrease in tumour incidence and improvement in depressive-like behaviours through modulation of the BDNF/TrKβ/β-catenin axis in the prefrontal cortex.
ABSTRACT
In addition to physical problems, depression is considered to be one of the most important challenges for patients with various types of cancers, particularly colorectal cancer. Inflammation and upregulation of brain neurotrophic factors are two major links between cancer and depression. In this study, we aimed to evaluate the alleviative effects of quercetin and exercise training on depressive-like behaviours in rats with 1,2-dimethylhydrazine (DMH)-induced colorectal cancer and to investigate the underlying mechanisms. Animals were assigned into the following five groups: (i) control group; (ii) DMH (20 mg kg s.c., once a week for 10 weeks); (iii) DMH for 10 weeks, followed by quercetin (50 mg kg p.o., once per week) for 12 weeks; (iv) DMH for 10 weeks, followed by exercise training for 12 weeks; and (v) DMH for 10 weeks, followed by quercetin and exercise training for 12 weeks. The DMH-treated rats showed an increase in depressive-like behaviours in both open field and forced swimming tests. Histopathological examination revealed neural damage and reduced Nissl bodies in the prefrontal cortex. In addition, administration of DMH increased inflammatory cytokines in the serum, prefrontal cortex and tumour tissues and decreased the expression levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase β receptor (TrKβ) and β-catenin in the cortex. In contrast, treatment with quercetin and exercise training effectively alleviated all the above-mentioned DMH-associated behavioural, biochemical and histopathological alterations without changing its anti-tumour activity. Taken together, our results show that the combination of quercetin and exercise training exerts potent anti-tumour and anti-depressive effects through suppression of inflammation and upregulation of the BDNF/TrKβ/β-catenin axis in the prefrontal cortex.
Topics: 1,2-Dimethylhydrazine; Animals; Brain-Derived Neurotrophic Factor; Colorectal Neoplasms; Cytokines; Depression; Male; Physical Conditioning, Animal; Prefrontal Cortex; Quercetin; Rats; Rats, Wistar; Receptor, trkB; Signal Transduction; beta Catenin
PubMed: 32681548
DOI: 10.1113/EP088605 -
British Journal of Cancer Oct 1987People at risk from coronary heart disease and large bowel cancer are drawn from the same urbanised, industrialised Western populations. Whilst changes in blood lipids...
People at risk from coronary heart disease and large bowel cancer are drawn from the same urbanised, industrialised Western populations. Whilst changes in blood lipids are well recognised in heart disease, little is known of their role in large bowel cancer. This study investigates serial alterations in blood lipids in the 1,2-dimethylhydrazine (DMH) rat model of colon cancer. Eighty Wistar rats received a 5 weekly regimen of DMH. At week 10, and at 5 weekly intervals until week 40, random groups of 10 rats were killed and blood taken for total and free cholesterol, phospholipids, triglycerides and liver enzymes. All colonic neoplasms were histologically classified either as adenomas or carcinomas with groups being allocated into tumour-free (n = 16) or tumour-bearing (n = 54), the latter group being further sub-divided into animals with adenoma alone (n = 8) and those with carcinoma (n = 46). Results were considered both sequentially and according to tumour status. Sequential results showed that with increase in colonic neoplasms with time there were accompanying increases in free and % free cholesterol and in phospholipids (P less than 0.001). There were no changes in total cholesterol, triglycerides or liver enzymes. Results according to tumour status showed that whilst there was no difference in total cholesterol or triglycerides between tumour-free and tumour-bearing rats, there was a significant increase in free (P less than 0.01) and % free cholesterol (P less than 0.001) and a decrease in phospholipids in the tumour-bearing animals (P less than 0.001). There was no difference in any serum lipid between tumour-free and adenoma-bearing rats. In animals with carcinoma, while there was no difference in total cholesterol or triglycerides, there was an increase in free (P less than 0.005) and % free cholesterol (P less than 0.001) and a decrease in phospholipids (P less than 0.001) compared to tumour-free rats. The data show for the first time a clear relationship between blood lipids and the presence or absence of large bowel cancer.
Topics: 1,2-Dimethylhydrazine; Adenoma; Alanine Transaminase; Alkaline Phosphatase; Animals; Carcinoma; Cholesterol; Colonic Neoplasms; Dimethylhydrazines; Female; Lipids; Phospholipids; Rats; Rats, Inbred Strains; Triglycerides
PubMed: 3689662
DOI: 10.1038/bjc.1987.222 -
Molecules (Basel, Switzerland) May 2021This study aimed to evaluate the cancer chemopreventive activity of vanillic acid (VA) in diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon...
This study aimed to evaluate the cancer chemopreventive activity of vanillic acid (VA) in diethylnitrosamine- and 1,2-dimethylhydrazine-induced liver and colon carcinogenesis in rats. VA did not induce the formation of hepatic glutathione -transferase placental form (GST-P) positive foci and colonic aberrant crypt foci, demonstrating no carcinogenic activity. VA (75 mg kg body weight) could significantly reduce the number and areas of hepatic GST-P positive foci when administered before carcinogen injections, but no such effect was seen when it was administered after carcinogen injection. No protection was seen in the colon when VA was treated before or after carcinogen injection. Immunohistochemical studies demonstrated the decreased expression of proliferating cell nuclear antigen and the induction of apoptosis. Mechanistic studies showed that VA significantly induced the expression of and genes, which are associated with the detoxification system. Likewise, the antiproliferative effect was noticed by the reduction of expression. The apoptotic activity may be due to the upregulation of and levels and downregulation of the level. These data suggest that VA exhibited significant protection against diethylnitrosamine- and 1,2-dimethylhydrazine-induced hepatocarcinogenesis, which might be related to the induction of the detoxifying enzyme, the reduction of proliferation and the induction of apoptosis.
Topics: 1,2-Dimethylhydrazine; Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Carcinogenesis; Cell Proliferation; Diethylnitrosamine; Gene Expression Regulation, Neoplastic; Liver Neoplasms; Male; Organ Size; Protective Agents; Rats, Wistar; Vanillic Acid; Rats
PubMed: 34063148
DOI: 10.3390/molecules26092718 -
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